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ABSTRACTS PRESENTED FROM AARC

ABSTRACTS PRESENTED FROM AARC

Utility Of A Modified PIRO (Predisposition, Injury, Response, Organ Failure) Model For Predicting Kidney Failure In Patients With ACLF- A Multinational Cohort Study

Rakhi Maiwall1, Shiv K. Sarin1, Chandan K. Kedarisetty1, Richard Moreau28,14, Suman Kumar29, Zaigham Abbas5, Deepak N. Amarapurkar6, Ankit Bhardwaj2, Ajeet S. Bhadoria2, Chhagan Bihari3, Amna S. Butt7, Chan Albert8, Yogesh K. Chawla10, Abdulkadir Dokmeci11, Hasmik Ghazinyan12, Saeed S. Hamid7, Cho Mong13, George K. Lau15, Guan Huei Lee16, Laurentius A. Lesmana17, Mamun A. Mahtab18, Qin Ning19, Viniyendra Pamecha4,Diana A. Payawal20, Archana Rastogi3, Salimur Rahman18,Mohamed Rela21, Amrish Sahney1, Vivek A. Saraswat22, Samir R. Shah23, Gamal Shiha24, Barjesh C. Sharma25, Manoj Kumar1, Soek Siam Tan26, Chitranshu Vashishtha1, Ashok Choudhary1, Man Fung Yuen9, Osamu Yokosuka27; 1Hepatology, ILBS, New Delhi, India; 2Rsearch, ILBS, New Delhi, India; 3Pathology, ILBS, New Delhi, India; 4Hepatobiliary Surgery, ILBS, New Delhi, India; 5Sindh Institute of Urology and transplantation, Karachi, Pakistan; 6Department of Gastroenterology and Hepatology, Bombay Hospital and Medical Research, New Delhi, India; 7Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan; 8Department of Surgery, The University of Hong Kong, Hong Kong, Chile; 9Department of Medicine, The University of Hong Kong, Hong Kong, China; 10Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; 11Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey; 12Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia; 13Hallym University Chuncheon Sacred Heart Hospital, Gangwon-Do, Republic of Korea; 14Liver Unit, Beaujon hospital, Paris, France; 15Department of Hepatology, Beijing 302 Hospital, Beijing, China; 16National University Health system, Singapore, Singapore; 17University of Indonesia, Jakarta, Indonesia; 18Department of Hepatology, Bangabandhu Sheikh Mujib Medical university, Dhaka, Bangladesh; 19Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Wuhan, China; 20Department of Hepatology, Cardinal Santos Medical center, Manila, Philippines; 21Institute of Liver diseases and Transplantation, Global Health city, Chennai, India; 22Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India; 23Department of Gastroenterology and Hepatology, Global Hospitals, Mumbai, India; 24Department of Internal Medicine, Egyptian Liver Research Institute and Hospital, Cairo, Egypt; 25Department of Gastroenterology, GB Pant Hospital, New Delhi, India; 26Department of Gastroenterology and Hepatology, Selayang Hospital, Kuala Lumpur, Malaysia; 27Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba, Japan; 28Center for Research in Inflammation (CRI), Inserm and Paris Diderot University, Paris, France; 29Command Hospital,

Kolkata, India

Background and Aim: Kidney dysfunction is an ominous sign in ACLF patients. There is however, limited data on predictors of kidney dysfunction in ACLF. The PIRO classification was developed to stratify patients with sepsis with different outcomes. We developed a modified PIRO model (Predisposition, Injury,Response,Organ failure) to identify variables for predicting kidney failure in a multicentric, multinational cohort of ACLF patients(APASL definition).

Patients and Methods: Prospectively collected data from 17 Asian countries using the APASL ACLF Research Consortium (AARC) database was analyzed and logistic regression models were developed to assess the best set of covariates for each of the components of PIRO and a combined PIRO model for predicting kidney failure in patients with ACLF. Kidney failure was defined as anincrease of serum creatinine ≥ 2 mg/dl or requirement of renal replacement therapy. Factors considered for univariate analysis for Predisposition included patient demographics, severity and etiology of underlying liver disease, baseline biochemical parameters, presence of ascites,comorbidities including chronic kidney disease; for Injury- diuretic use, nephrotoxicity, bacterial infections, variceal bleed; for Response-components of systemic inflammatory response syndrome and for Organ failure-extrarenal organ failures i.e. cerebral, circulatory and respiratory defined according to CLIF-SOFA score.

Results: Of 1365 patients with ACLF (age 44 ±12.9 years, 83% males) with MELD score of 32.6 ± 9.4, 29% developed kidney failure. Factors significant (p,OR, 95% CI) on multivariate analysis for P component were high baseline MELD (≥30) (<0.001, 1.72, 1.34-2.2) and low serum sodium (<130mEq/l) (0.002, 1.4, 1.14-1.9); for I component, bacterial infections (0.02, 1.4, 1.04-1.96); for R component, leucocytosis (0.03, 1.3, 1.02- 1.71); for O component, circulatory failure (<0.0001, 4.6, 3.2-6.7) and cerebral failure (<0.001,2.7, 2.1-3.6). The combination of these four components into a single-value predictor of kidney failure in the combined PIRO model identified circulatory failure (OR 5.8, 95% CI 3.1-11.1) and cerebral failure (OR 2.1, 95% CI 1.2-3.7) as the most significant predictors. Amongst all organ failures, presence of circulatory failure at baseline was the most significant predictor of mortality (OR 1.8, 95% CI 1.1-3.3).

Conclusions: The PIRO model could be a novel approach to identify and stratify ACLF patients at risk of kidney failure. Kidney failure is commonly associated with presence of extra-renal organ failures at baseline amongst which circulatory failure predicts mortality independent of both renal and other organ failures.

 

Liver failure determines the extra-hepatic organ failure and outcome in patients with acute-on-chronic liver failure: Analysis of 1363 patients of AARC Data Base

Chandan K. Kedarisetty1, Shiv K. Sarin1, Lovkesh Anand1, Zaigham Abbas4, Deepak N. Amarapurkar5, Ankit Bhardwaj2, Ajeet S. Bhadoria2, Chhagan Bihari3, Amna S. Butt6, Ashok Choudhary1, Chan Albert7, Yogesh K. Chawla9, Abdulkadir Dokmeci10, Hitendra K. Garg1, Hasmik Ghazinyan11, Saeed S. Hamid6, Ankur Jindal1, Naveen Kumar1, Avinash Kumar1, Guan Huei Lee12, Laurentius A. Lesmana13, Mamun A. Mahtab14, Rakhi Maiwall1, Qin Ning15, Devraj Rangegowda1, Archana Rastogi3, Amrish Sahney1, Samir R. Shah16, Gamal Shiha17, Barjesh C Sharma18, Manoj Kumar1, Saggere M. Shasthry1, Soek Siam Tan19, Chitranshu Vashishtha1, Man-Fung Yuen8, Osamu Yokosuka20; 1Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; 2Research, Institute of Liver and Biliary Sciences, New Delhi, India; 3Pathology, Institute of Liver and Biliary Sciences, New Delhi, India; 4Hepatogastroenterology, Sindh Institute of Urology and transplantation, Karachi, Pakistan; 5Gastroenterology and Hepatology, Bombay Hospital and Medical Research, Mumbai, India; 6Medicine, Aga Khan university hospital, Karachi, Pakistan; 7Surgery, University of Hong Kong, Hong Kong, China; 8Medicine, University of Hong Kong, Hong Kong, China; 9Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; 10Gastroenterology, Ankara University School of Medicine, Ankara, Turkey; 11Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia; 12Gastroenterology and Hepatology, National University Health system, Singapore, Singapore; 13Hepatology, University of Indonesia, Jakarta, Indonesia; 14Hepatology, Bangabandhu Sheikh Mujib Medical university, Dhaka, Bangladesh; 15Infectious Disease, Tongji Hospital of Tongji Medical College, Wuhan, China; 16Gastroenterology and Hepatology, Global Hospitals, Mumbai, India; 17Internal Medicine, Liver Research Institute and Hospital, Cairo, Egypt; 18Gastroenterology, GB Pant Hospital, New Delhi, India; 19Gastroenterology and Hepatology, Selayang Hospital, Selayang, Malaysia; 20Gastroenterology and Nephrology, Graduate School of Medicine,- Chiba University, Chiba, Japan

Background and Aims: Acute-on-chronic liver failure (ACLF) is a distinct syndrome characterized by an acute insult on underlying chronic liver disease culminating in extra-hepatic organ failure and high mortality.The only definitive treatment is liver transplantation. It is likely that interventions may be helpful, if employed before extra-hepatic organ failure develop as there is a potential of reversibility. We aimed at defining and grading liver failure in ACLF patients, its impact on extra-hepatic organ failure and patient outcome. Patients and Methods: It was a retrospective- prospective data collection of 1363 patients from 17 university hospitals across Asia- Pacific from October 2012 to December 2013.

Results: The overall mortality on day 28 was 52.1% and day 90 was 59.7%; 34.8% occurring in the first 2 weeks. The common hepatotropic acute insults were alcohol (563, 41.3%), viral infections (452, 33.1%), drug induced liver injury (93, 6.82%) and flare of autoimmune (35, 2.6%) and Wilson’s disease (22, 1.6%). The chronic etiologies included alcohol (645, 47.3%), viral (335, 24.6%), non-alcoholic fatty liver disease (NAFLD)/cryptogenic (277, 20.2%) and others (106, 7.9%). The CLIF SOFA score was evaluated to assess organ failure in the Asian cohort. Even in the absence of any extra-hepatic organ failure, 39% mortality was observed in 28 days, primarily due to liver failure. The AARC grading of liver failure (Class I,II and III), based on bilirubin, INR and grade of hepatic encephalopathy correlated with mortality; 25.5% (75/ 106) in Class 1, 52.8% (336/636) in Class II and 78.8% (167/212) in Class III (AUROC 0.72, p-0.000).

Conclusions: Our results provide conclusive evidence that ACLF should be defined based on liver failure. Extra-hepatic organ failure (s) is likely to be a consequence of worsening liver failure. The proposed AARC grading of liver failure needs to be further validated.

 

APASL 2015

Defining a ‘golden window’ period and relevance of systemic inflammatory response syndrome (SIRS) in acute on chronic liver failure (ACLF) a tool for intervention and improved survival

Ashok Choudhury1 , Shiv Kumar Sarin1 , K. N. Chndan Kumar 2 , C. Vashishtha1 , Z. Abbas3 , D. Amarpurkar4 , A. S. Butt5 , A. Chan6 , Y. K. Chawla7 , A. K. Dokmeci8 , H. Garg9 , H. Ghazinyan10, S. S. Hamid11, Ji-dong Jia12, M. Kumar1 , Gh Lee13, La Lesmana14, M. Mahtab15, Rakhi Maiwal1 , R. Moreau16, Q. Ning17, V. Pamecha18, Da Payawal19, S. Rahman15, D. Samuel20, S. Shah21, G. Shiha22, Bc Sharma23, S. S. Tan24, Mf Yuen25, O. Yokosuka26, H. C. Devarbhabi27, C. E. Eapen28, Apasl Aclf Working Party29Institute of Liver and Biliary Sciences Hepatology New Delhi-India1 , Narayana Health City Gastroenterogy Banglore-India2 , Sindh Institute of Urology and Transplantation Hepatogastroenterology Karachi-Pakistan3 , Bombay Hospital and Medical Research Gastroenterology and Hepatology Mumbai-India4 , Aga Khan University Hospital Department of Medicine Karachi-Pakistan5 , The University of Hong Kong Hepatobiliary and Pancreatic Surgery, and Liver Transplantation Hong Kong-China6 , Post Graduate Institute of Medical Education and Research Hepatology Chandigarh-India7 , Ankara University School of Medicine Gastroenetrology AnkaraTurkey8 , Apollo Hospital Gastroneterology,hepatology New DelhiIndia9 , Nork Clinical Hospital of Infectious Diseases Hepatology Yerevan-Armenia10, Aga Khan University Hospital Medicine Karachi-Pakistan11, Beijing Friendship Hospital, Capital Medical University Liver Research Center Beijing-China12, National University Health System Department of Gastroenterology and Hepatology Singapore-Singapore13, University of Indonesia Division of Hepatology Jakarta-Indonesia14, Bangabandhu Sheikh Mujib Medical University Department of Hepatology Dhaka-Bangladesh15, Labex Inflamex, Universite´ Paris Diderot Paris 7 Inserm, U1149, Centre De Recherche Sur L Paris-France16, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology Department of Infectious Disease Wuhan-China17, Institute of Liver and Biliary Sciences Department Hepatobiliary Surgery and Liver Transplant New Delhi-India18, Cardinal Santos Medical Center Department of Hepatology Manila-Philippines19, Hoˆpital Paul Brousse, Inserm Centre He´patobiliarie Villejuif-France20, Global Hospitals Department of Gastroenterology and Hepatology MumbaiIndia21, Egyptian Liver Research Institute and Hospital Department of Internal Medicine Cairo-Egypt22, Gb Pant Hospital Gastroenterology New Delhi-India23, Selayang Hospital Department of Hepatology Kepong-Malaysia24, The University of Hong Kong Hepatobiliary and Pancreatic Surgery, and Liver Transplantation, Department of Surgery and Department of Medicine Hong KongChina25, Graduate School of Medicine, Chiba University Department of Gastroenterology and Nephrology Chiba-Japan26, St Johns Medical College Gastroenterology Banglore-India27, Christian Medical College Gastroenterology and Hepatology Vellore-India28, Institute of Liver and Biliary Sciences Aarc New Delhi-India29

Background and aims: Systemic Inflammatory Response Syndrome (SIRS) is an early marker of sepsis and ongoing inflammation. Sepsis is the most common cause of mortality. The aim is to study the natural course of SIRS and sepsis in a hospitalized ACLF cohort without SIRS, sepsis at baseline and to define a window period for possible intervention.

 Methods: Consecutive hospitalized patient of ACLF were prospectively evaluated for the development of SIRS/sepsis and associated complications till 90 days follow up, liver transplant or death. All patients received standard medical care, sepsis screening was done for initial 15 days, followed by ‘on suspicion’ screening.

Results: 201 patients with median age 46 yr (IQR = 38–45), male (91 %) and majority of ethanol (47 %) etiology. New onset SIRS, sepsis and septic shock at the end of first week were (77.6, 10 and 1 %) respectively. The time to development of SIRS, sepsis were 6.18 ± 1.7 and 7 days (IQR 4–7) respectively. Rate of development or resolution of SIRS 11–12 % per day. Development of SIRSassociated with procalcitonin positivity (P = 0.05). Increasing no of organ failure (0, 3, 4) associated with higher incidence of SIRS (24, 87.5 and 100 % respectively, P\0.05). SIRS at D7 leads to a median survival (12 vs. 29 weeks), first week mortality (23 % vs. none, P\0.005) and 90 days mortality of (51.9 % vs. 37.8 %, P = 0.12).

Conclusion: SIRS and its dynamicity is an important predictor of early sepsis, organ failure and survival in ACLF. Prompt use of prophylactic antibiotics with onset SIRS and rigorous septic screen during in the Golden window could improve outcome.

EASL 2016

THE DECISION FOR LIVER TRANSPLANT IN ACUTE ON CHRONIC LIVER FAILURE (ACLF) - FIRST WEEK IS THE CRUCIAL PERIOD - ANALYSIS OF THE APASL ACLF RESEARCH CONSORTIUM (AARC) PROSPECTIVE DATA OF 1021 PATIENTS

A.K. Choudhury, M.K. Sharma, R. Maiwal2, P. Jain3, M.A. Mahtab4, Y.K. Chawla5, S.S. Tan6, Q. Ning7, H. Devarbhavi8, D.N. Amarapurkar9,C.W. Kim10, S.S. Sadiq11, A.S. Butt11, C. Eapen12, H. Ghazinyan13, C. yu14,A. Sood15, G.H. LEE16, Z. Abbas17, G. Shiha18, L.A. Lesmana19,D.A. Payawal20, K.A. Dokmeci21, G.K. Lau22, S.K. Sarin, APASL ACLFWorking party. Hepatology and Liver Transplant; 2Hepatology; 3Dept of Research, Institute of Liver and Biliary Sciences, New Delhi, India; 4Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 5Hepatology, Pgimer, Chandigarh, India; 6Selayang Hospital University of Malaya, Malaysia, Malaysia; 7Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 8St John Medical College, Bangalore; 9Bombay Hospital & Medical Research Centre, Mumbai, India; 10Division of Hepatology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, South Korea; 11Aga Khan University Hospital, Karachi, Pakistan; 12Hepatology, CMC, Vellore, India; 13Nork Clinical Hospital of Infectious Diseases, Armenia, Armenia; 14Hepatology Institute Capital Medical University, Beijing, China; 15CMC, Ludhiana, India; 16Department of Gastroenterology & Hepatology, National University Health System, National University of Singapore, Singapore, Singapore; 17Sindh Institute of Urology and Transplantation, Karachi, Pakistan; 18Egyptian Liver Research Institute and Hospital, Egypt, Egypt; 19Digestive Disease & Oncology Centers, Medistra Hospital, Jakarta, Indonesia; 20Fatima Medical University Hospital, Manila, Philippines; 21Ankara University School of Medicine, Ankara, Turkey; 22Institute of Translational Hepatology, Beijing, China

Background and Aims: ACLF is associated with rapidly progressive liver failure with high short-term mortality. Early identification and intervention for acute insult, aggressive critical care, support for organ failures and timely consideration of liver transplant may improve survival. We investigated the predictors of outcome and the dynamic changes to define the ideal timing of liver transplantation. Methods: The patients diagnosed to have ACLF as per APASL definition were recruited from 40 centres across Asia Pacific. The data was prospectively collected on a predefined format in the database from October 2012 to July 2015 Clinical events, laboratory parameters, disease severity score, organ failures were analysed at baseline and their dynamic changes at D4 and D7 to predict the 28 and 90 days survival outcome.

Results: Of the 2312 enrolled patients, complete follow up data of 1021 was available till last follow-up and was analyzed. The mortality was 11.3%, 22.1% and 43.5% respectively within 4, 7 and 28 day of admission. At presentation, age (HR 1.10, 95 CI = 1.00–1.02), total bilirubin (HR 1.03 95 CI = 1.02–1.04), creatinine (HR 1.23 95 CI = 1.18– 1.27), INR (HR 1.31 95 CI = 1.25–1.35), HE grade (HR 2.32 95 CI = 2.05– 2.63), Lactate (HR 1.18 95 CI = 1.15–1.21) were independent predictors of 28 days mortality. Absence of new onset HE or AKI within first 4 days, a decline in total bilirubin by 0.43 mg/dL, creatinine by 0.31 mg/dL, INR by 0.34 by day 7 predicted survival ( p < 0.001). Bilirubin <20.5 mg/dL, Creatinine <0.94 mg/dL, INR <2.18 and MELD score <27 at any time point in first week was associated with 100% survival. A bilirubin of >22 mg/dL, HE Grade –III or IV, INR >2.5, with either creatinine of >1 mg/dL or lactate 1.5 mmol/lit at baseline or persistence of same at D4 or D7 leads to 100% mortality within 28 days.

Conclusions: ACLF is a serious condition with high short term mortality. The baseline parameters and their change in first week of diagnosis could identify the patient with universal fatality. Emergent live donor LT or special allocation policy for DDLT should be explored in the first week.

 

ACUTE ON CHRONIC LIVER FAILURE SECONDARY TO DRUGS: CAUSES, OUTCOME AND PREDICTORS OF MORTALITY

H. Devarbhavi1, A.K. Choudhury2, V.V. Reddy3, M.K. Sharma2, R. Maiwall2, P. Jain4, M. Al-Mahtab5, Y.K. Chawla6, S.S. Tan7, Q. Ning8, S.S. Hamid9, C.E. Eapen10, H. Ghazinyan11, Z. Duan12, A. Sood13, G.H. Lee14, Z. Abbas15, G. Shiha16, L.A. Lesmana17, D.A. Payawal18, G. Kumar4, S.K. Sarin2, APASL ACLF Working party. 1ST John Medical College, Bangalore; 2Hepatology, Institute of Liver and Biliary Sciences, New Delhi; 3Hepatology, ST John Medical College, Bangalore; 4Research, Institute of Liver and Biliary Sciences, New Delhi, India; 5Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 6Hepatology, PGIMER, Chandigarh, Chandigarh, India; 7Hepatology, Selayang Hospital University of Malaya, Malaysia, Malaysia; 8Hepatology, Institute of Infectious Disease, China; 9Hepatology, Aga Khan University Hospital, Karachi, Pakistan; 10Hepatology, CMC, Vellore, India; 11Hepatology, Nork Clinical Hospital of Infectious Diseases, Armenia; 12Hepatology, Hepatology Institute Capital Medical University, Beijing, China; 13Hepatology, CMC, Ludhiana, India; 14Hepatology, Department of Gastroenterology & Hepatology, National University Health System, National University of Singapore, Singapore, Singapore; 15Hepatology, Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan; 16Hepatology, Egyptian Liver Research Institute And Hospital, Egypt, Egypt; 17Hepatology, Digestive Disease & Oncology Centers, Medistra Hospital, Jakarta, Indonesia; 18Hepatology, Fatima Medical University Hospital, Valenzuela MetroManila, Valenzuela, Philippines

Background and Aims: Acute hepatic decompensation in patients with chronic liver disease carries significant short term mortality. Although a number of precipitating events may trigger acute on chronic liver failure (ACLF) the impact of drugs on outcome has not been studied. We evaluated drugs as precipitating factors in ACLF in a prospectively enrolled cohort of patients from the AARC consortium.

Methods: ACLF was defined as per APASL criteria (Hepatol Int2009;3:269). ACLF-APASL research consortium (AARC) includes 24 centres from Asia-pacific region. We investigated the influence of drugs, both antituberculosis therapy (ATT) and non ATT (complementary and alternative medicines (CAM), methotrexate, interferons, others) as acute precipitants in causing ACLF. We studied their baseline clinical, laboratory characteristics including 4 and 7 day values and its impact on mortality. Univariate and multivariate analysis was carried out including Cox proportional regression analysis and a Kaplan Meier analysis curve.

Results: Of the 2224 patients enrolled in AARC, drugs constituted 6.5% (N = 145) as precipitating events. Complete data was available for 136 patients. Anti-tuberculosis therapy (ATT) and non-ATT constituted 62 (46%) and 74 (54%) cases respectively of which 36 (58%) and 47 (63.5%) died. The majority of underlying chronic liver diseases were secondary to cryptogenic and alcoholic liver disease (>80%). Characteristics between survivors vs non survivors were as follows: Hemoglobin: 11.7 vs 10.8 ( p = 0.02), WBC count (9.6 vs 13.5, p = <.001), serum creatinine (SCr) (0.9 vs 1.6, p = 0.002, International normalized ratio (INR)) (2.3 VS 3, p = <0.001, presence of ascites ( p = 0.04)) and encephalopathy ( p = 0.006). On multivariate analysis the following factors were associated with survival: SCr and (INR) p < .0001(at baseline), INR, serum lactate (S Lac) and serum alkaline phosphatase on day 4 ( p < .01) and S Lac on day 7 ( p = .002). Using Cox regression analysis SCr and INR were the best predictors of mortality ( p < .0001) (Hazard ratio 1.4 and 1.5 respectively). The overall median survival time was 23.5 days (range 12.6–34.7), which was shorter for non ATT drugs compared to ATT drugs (22 vs 31 days).

Conclusions: Drugs as precipitating events constitute 6.5% of cases in ACLF of which ATT and CAM are the commonest causes. Mortality is significant (61%). Presence of encephalopathy, ascites and elevated serum creatinine, INR, and serum lactate are predictors of survival.

 

PORTAL HEMODYNAMICS PREDICTS THE OUTCOME IN SEVERE ALCOHOLIC HEPATITIS PRESENTING AS ACUTE-ON-CHRONIC LIVER FAILURE

A.K. Choudhury1, M.K. Sharma1, R. Maiwal2, P. Jain3, M.A. Mahtab4, Y.K. Chawla5, S.S. Tan6, Q. Ning7, H. Devarbhavi8, D.N. Amarapurkar9, C.W. Kim10, S.S. Sadiq11, A.S. Butt11, C. Eapen12, H. Ghazinyan13, C. Yu14, A. Sood15, G.H. LEE16, Z. Abbas17, G. Shiha18, L.A. Lesmana19, D.A. Payawal20, K.A. Dokmeci21, G.K. Lau22, S.K. Sarin1, and APASL ACLFWorking party. 1Hepatology and Liver Transplant; 2Hepatology; 3Dept of Research, Institute of Liver and Biliary Sciences, New Delhi, India; 4Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 5Hepatology, PGIMER, Chandigarh, India; 6Selayang Hospital University of Malaya, Malaysia, Malaysia; 7Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 8St John Medical College, Bangalore; 9Bombay Hospital & Medical Research Centre, Mumbai, India; 10Division of Hepatology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, South Korea; 11Aga Khan University Hospital, Karachi, Pakistan; 12Hepatology, CMC, Vellore, India; 13Nork Clinical Hospital of Infectious Diseases, Armenia, Armenia; 14Hepatology Institute Capital Medical University, Beijing, China; 15CMC, Ludhiana, India; 16Department of Gastroenterology & Hepatology, National University Health System, National University of Singapore, Singapore, Singapore; 17Sindh Institute of Urology and Transplantation, Karachi, Pakistan; 18Egyptian Liver Research Institute And Hospital, Egypt, Egypt; 19Digestive Disease & Oncology Centers, Medistra Hospital, Jakarta, Indonesia; 20Fatima Medical University Hospital, Manila, Philippines; 21Ankara University School of Medicine, Ankara, Turkey; 22Institute of Translational Hepatology, Beijing, China

Background and Aims: During acute-on-chronic liver failure (ACLF=, the progressive liver failure is associated with rise in portal pressure. Development of variceal bleed, sepsis and organ failures often related to the severity of portal hypertension in addition to the inciting acute injury. The aim is identify the changes in portal and systemic hemodynamics in patients of ACLF caused by Severe Alcoholic Hepatitis (SAH) or other etiologies and their influence on organ failure and survival

Methods: ACLF patients as by APASL were enrolled into the AARC database and followed prospectively for initial 90 days. Clinical events, laboratory parameters, disease severity score, survival were compared for the acute insult i.e. SAH against other etiologies. Median stiffness (KPa), Transient elastography (Fibroscan™), Transjugular portal hemodynamic parameters (HVPG), cardiac catheterization [mean Pulmonary Artery pressure (MPAP), PCWP, and formula based systemic hemodynamic variables [SVRI,PVRI, Cardiac Output (CO),Cardiac Index (CI)] were compared in SAH against other acute insults in predicting AKI, sepsis, organ failure, variceal bleed and survival.

Results: 308 patients (150 SAH, 158 other etiologies) with TJLB were analyzed. At baseline the MELD, SOFA, bilirubin, creatinine, mortality (51.5% vs 48.5%,p = 0.29) were comparable. SAH group were younger [(40.8 + 8.7) vs. (46.6 + 12.8) years, p < 0.001] with higher portal pressure i.e. HVPG [(18.5 + 5.0) vs. (16.7 + 5.1) mm of Hg, p = 0.003] and lower Hb [(10.6 + 1.7) vs. (11.3 + 1.9) gm/dL. p = 0.001]. HR, MAP, CO, CI, SVRI, PVRI were comparable in both the groups. LSM, HVPG, PCWP, MPAP, variceal grade, INR, serum Na were predictors of 90 days mortality. In multivariate analysis HVPG [OR = 1.02, 95CI (1.01–1.13),p = 0.01],            MPAP [OR = 1.04, 95CI(1.03–1.12) were independent predictor of mortality. HVPG > 17.2 mm Hg correlate to variceal bleed  ( p = 0.03), AKI             ( p = 0.09) and sepsis      ( p = 0.07) within 15         days. HVPG correlated           to low platelet ( p = 0.02) and presence of RCS ( p = 0.003) but not to the grade of varices, TNF-alpha, CRP and Ferritin. The HVPG > 19.5 mm Hg was associated with mortality 28% vs. 42%, p=

Conclusions: SAH is associated with higher portal pressure than other etiologies irrespective of variceal grade and is an independent predictor of mortality. Presence of RCS on varices or low platelet, not the inflammatory markers correlate to portal hemodynamics.

 

BETTER SURVIVAL IN PATIENTS WITH HEPATITIS E VIRUS C.F. TO OTHER ACUTE INSULTS CAUSING ACUTE-ON-CHRONIC LIVER FAILURE (ACLF) – APASL-ACLF RESEARCH CONSORTIUM (AARC) DATABASE

A. Goel1, C.E. Eapen1, A. Choudhary2, M.K. Sharma2, R. Maiwall2, M. Al Mahtab3, Y.K. Chawla4, S.-S. Tan5, Q. Ning6, H. Devarbhavi7, D.N. Amrapurkar8, C.W. Kim9, S.S. Hamid10, A.S. Butt10, H. Ghazinyan11, Z. Duan12, C. Yu12, A. Sood13, G.H. Lee14, Z. Abbas15, G. Shiha16, L.A. Lesmana17, D.A. Payawal18, A. Kadir Dokmeci19,M.F. Yuen20, G.K. Lau21, Md.F. Karim22, J.D. Sollano23, S.K. Sarin2 and APASL-ACLF working party. 1Hepatology, Christian Medical College, Vellore; 2Institute of Liver and Biliary Sciences, New Delhi, India; 3Bangabandhu Sheikh Mujib Medical university, Dhaka, Bangladesh; 4PGIMER, Chandigarh, India; 5Selayang Hospital University of Malaya, Malaysia, Malaysia; 6Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 7St John Medical College, Bangalore; 8Bombay Hospital & Medical Research Centre, Mumbai, India; 9Division of Hepatology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, South Korea; 10Aga Khan University Hospital, Karachi, Pakistan; 11Nork Clinical Hospital of Infectious Diseases, Armenia, Armenia; 12Hepatology Institute Capital Medical University, Beijing, China; 13Christian Medical College, Ludhiana, India; 14Department of Gastroenterology & Hepatology, National University Health System, National University of Singapore, Singapore, Singapore; 15Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan; 16Egyptian Liver Research Institute And Hospital (ELRIAH), Cairo, Egypt; 17Disease & Oncology Centers, Medistra Hospital, Jakarta, Indonesia; 18Fatima Medical University Hospital, Valenzuela MetroManila, Manila, Philippines; 19Ankara University School of Medicine, Ankara, Turkey; 20Queen Mary Hospital, Hong Kong, Hong Kong; 21Institute of Translational Hepatology, Beijing, China; 22Department of Hepatology, Sir Salimullah Medical College Mitford Hospital, Dhaka, Bangladesh; 23University of Santo Tomas, España Blvd, Manila, Philippines

Background and Aims: The current study aims to analyse impact of acute insult on short term mortality in ACLF patients.

Methods: AARC, consisting of multiple tertiary centers spread across Asia-Pacific regions, maintains an online database for prospectively accruing data on patients with ACLF, defined as per APASL criteria. The patients were managed as per individual institutional protocols. We compared short term survival in ACLF patients with acute insult caused by alcohol (group 1), Hepatitis E (group 2) and no identifiabe cause (cryptogenic, group 3).

Results: From July 2007 to April 2015, ACLF patients with acute insult which was alcohol related (group 1, n = 801, age: 41.9 ± 9.1 years, male: 782, MELD score: 29.4 ± 8.4), Hepatitis E related (group 2, n = 180, age:47.8 ± 13.6 years, male:148, MELD:28.3 ± 7.1) and cryptogenic (group 3, n = 118, age:47.2 ± 14.5; male: 80, MELD: 28.7 ± 10) were recruited. Short term mortality data was available in 978 (89%) of study patients with follow up duration of 182 (±329) days in group 1, 340 (±514) days in group 2 and 182 (±392) days in group 3. On Kaplan Meier analysis, the median survival in group 1 was 45 days (95% C.I:20–70 days) and group 3 was 47 days (95% C.I:16–78 days). In group 2, 63% survived the follow up period. Overall, group 1 had worse survival as compared to group 2 ( p-value: < 0.001) and similar survival as group 3 ( p-value: 0.4) (see Figure). Cumulative survival at 1 week was – group 1: 0.77 (0.018); group 2: 0.88 (0.03) and group 3: 0.7 (0.06). The proportion of patients with decreasing trend of MELD score over 7 days was similar in all groups (224/407 v/s 51/102 v/s 21/41; p-value: 0.6). On Cox proportional hazards model, controlling for baseline MELD score, as compared to group 1, group 2 had significantly lower hazard ratio (0.64, 95% C.I: 0.48–0.86, p- value:0.003); in contrast, group 3 had similar hazard ratio (1.2, 95% C. I: 0.84–1.7, p-value:0. 3) to group 1.

Conclusions: In this study conducted in 58 centres, across 18 countires, etiology of acute insult has a significant impact on prognosis of ACLF patients – those with Hepatitis E virus related acute insult tend to have better short term survival compared to those with alcohol related/cryptogenic acute insults. Further studies are needed to analyse the mechanisms of injury by different acute insults in ACLF.

 

AASLD 2016

 

Does the presence of cirrhosis influence on the mortality rate in patients with acute on chronic liver failure?

Sombat Treeprasertsuk1,2, Kessarin Thanapirom1,2, Roongruedee Chaiteerakij1,2, Ashok Choudhary3, Manoj Sharma3, Rakhi Maiwall4, Viniyendra Pamecha4, Richard Moreau4, Mamun A. Mahtab4, Yogesh K. Chawla4, Soek Siam Tan4, Harshad Devarbhavi4,Yu Chen4, Zhongping Duan4, Qin Ning4, Deepak N. Amarapurkar4, Saeed Hamid4, Amna S. Butt4, Hasmik Ghazinyan4, Guan Huei Lee4, Ajit Sood4, Laurentius A. Lesmana4, Gamal Shiha4, Diana A. Payawal4, Abdulkadir Dokmeci4, Shiv K. Sarin4; 1Medicine, Division of Gastroenterology, Chulalongkorn University, Patumwan, Thailand; 2Thai Red Cross, King Chulalongkorn Memorial Hospital, PATUMWAN, Thailand; 3Institute of Liver andBiliary Sciences, New Delhi, India; 4APASL ACLF Working Party (AARC)., New Delhi, India

Background: Currently, the APASL Acute-on-chronic liver failure (ACLF) research consortium (AARC) criteria includes non-cirrhotic chronic liver disease; CLD patients due to the evidence of high mortality rate (Sarin SK, Hepatol Int 2014). The basal CLD severity may play important role on outcomes. We aim to compare the 28-day and 90-day mortality rate of ACLF patients with and without cirrhosis.

Methods: AARC collected data prospectively from multicenter of ACLF patients during Oct, 2009

to Apr, 2016. Of 1621 patients, 637 of them (39%) were diagnosed as cirrhosis which defines as clinical presentations or biochemical or imaging evidence or histopathological confirmation advanced fibrosis. Baseline characteristics and the 28-day and 90-day mortality were recorded. The Kaplan-Meier ;K-M method was used to compare the mortality rate between two groups.

Results: Of a total of 1621 patients, 86.7% were male with mean age ± SD of 44.6±12 years. The most common acute insult were alcohol (48%), HBV reactivation (16%) and hepatitis E infection (7.5%). The baseline MELD score were 29 ± 7 and 52% of patients developed >2 organs failure.

The most frequent organs failure were liver (80%), coagulopathy (35%), and renal failure (23%). The 28-day and 90-day mortality rate were 39% and 50% respectively. Baseline characteristics showed that non-cirrhotic patients had significantly higher MELD score, number of organ failures than those cirrhotic patients. ACLF patient without cirrhosis had significantly

higher 28-day and 90-day mortality rate than cirrhotic patients as shown by the K-M survival curve in figure1.

Conclusion: Our data suggests that the 28-day and 90-day mortality rate

of ACLF patient without cirrhosis was significantly higher than those with cirrhotic, thus the presence of underlying cirrhosis at baseline should be evaluated due to its influence on mortality.

 

Etiology of chronic liver disease has no impact on the course and outcome of patients with Acute on Chronic Liver Failure

Yogesh K. Chawla , Sunil Taneja , Sahaj Rathi, Amritangshu Borkakoty, Ajay K. Duseja, Shiv K. Sarin; Hepatology, Post-graduate Institute of Medical Education and Research, Chandi-garh, India; Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India

Introduction: Acute on Chronic Liver Failure (ACLF) leads to higher mortality. Whether etiology of chronic liver disease influences the course and outcome of these patients is not well understood.. Aims: To compare presentation, course and out-come of patients with ACLF with a known etiology of chronic liver disease (KC) to those with cryptogenic chronic liver dis-ease (CC).

Methods: We retrospectively analysed our data-base of 1631 patients of APASL, ACLF Research Consortium (AARC), and included consecutive patients of ACLF according to APASL definition. Patients were divided into 2 groups based on whether etiology of chronic liver disease was known (KC) or cryptogenic (CC).. The clinical and laboratory parameters, organ failures, prognostic models and short term mortality rates were compared.

Results: Out of 1631 patients, 1469 patients were eligible for analysis. . 1277 (87%) patients were males and 192 (13%) were females .. Mean age of the patients was 44..9 ± 11..8yrs.. The etiology of chronic liver disease was alco-hol in 862 (58.. 7%), viral hepatitis in 293 (19.. 9%), cryptogenic in 146 (9..9%), non-alcoholic steatohepatitis in 81 (5..5%), auto-immune liver disease in 49 (3..3%) and others in 38 (2..6%) patients.. The most common cause of acute deterioration was alcoholic hepatitis 785 (50..8%) followed by viral hepatitis in 454 (29%),drug induced in 146 (9. .4%), autoimmune flare in 48 (3..1%), spontaneous bacterial peritonitis and sepsis in 24 (1..5%), tropical infections in 6 (0..4%), variceal bleed in 8 (0..5%), Wilsons disease in 7 (0..4%), surgery in 1 (0..1%) and unknown in 67 (4..3%) patients.. We compared 1323 patients in KC and 146 patients in CC group.. The patients were older (49..20±14. .32 vs 44. .38±11. .38yrs, p<0. .001) and females were more common in CC group versus KC group (30. .9% vs 6..5%, p<0..001).. CC had more severe coagulopathy (INR 2. .87 vs 2. .53, p= 0. .009). . There was no difference in inci-dence of ascites (91..3 % vs 86..9%, p=0..09) or encephalop-athy (49..6% vs 52..5%, p=0..51), severity of encephalopathy (p=0.. 88) or the frequency of sepsis (41.. 4% vs 44..1% p=0..53).. There was no difference in the number of organ failures (1..49 vs 1. .68,p=0. .06),CTP, (12 vs 11. .8, p=0. .24), MELD scores (29. .9 vs 29. .6, p=0. .39),CLIF-SOFA (11. .7 vs 11. .3, p=0. .20) and APACHE II (14. .92 vs 14. .93, p=0. .64) scores. . The 28 day (59% vs 62..1%, p=0..50) and 90 day (48..3 vs 51..1%, p=0. .51) survival between the two groups was similar.

Con-clusion: ACLF is a syndromic entity attributing poor prognosis in patients with chronic liver disease. . Our study shows that patients with cryptogenic chronic liver disease with ACLF behave similarly to those with known etiologies in terms of presentation, course and overall outcome.

 

APASL 2016

AARC-ACLF SCORE PREDICTS 30 DAY SURVIVAL BETTER THAN CLIF-SOFA AND MELD SCORES IN PATIENTS WITH ACLF

Ashok K Choudhury, Mamun A. Mahtab2, Yogesh K. Chawla3, Soek S. Tan4, Harshad Devarbhavi5, Saeed S. Hamid6, C.E. Eapen7, Hasmik Ghazinyan8, Zhongping Duan9, Ajit Sood10, Guan H. Lee11, A. K. Dokmeci12, Laurentius A. Lesmana13, Diana A. Payawal14, Rakhi Maiwall15, Manoj K. Sharma16, Priyanka Jain17, Guresh Kumar18, Shiv K. Sarin19, AARC Group20  1Institute of Liver and Biliary Sciences, New Delhi, India; 2Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 3PGIMER, Chandigarh, India; 4Selayang Hospital University of Malaya, Malaysia; 5St John Medical College, Bangalore, India; 6Aga Khan University Hospital, Karachi, Pakistan; 7C M C Vellore, India; 8Nork Clinical Hospital of Infectious Diseases, Armenia; 9Beijing Youan Hospital, Capital Medical University, Beijing, China; 10CMC, Ludhiana, India; 11Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 12Ankara University School of Medicine, Turkey; 13Digestive Disease & Oncology Centers, Medistra Hospital, Jakarta; 14Fatima Medical University Hospital, Valenzuela Metro Manila, Philippines; 15Institute of Liver and Biliary Sciences, New Delhi, India; 16Institute of Liver and Biliary Sciences, New Delhi, India; 17Institute of Liver and Biliary Sciences, New Delhi, India; 18Institute of Liver and Biliary Sciences, New Delhi, India; 19Institute of Liver and Biliary Sciences, New Delhi, India; 20APASL ACLF Working Group

Background and aims: Acute on chronic liver failure (ACLF) is associated with the rapid worsening of liver failure with high mor-tality. Prediction of survival and early intervention can improve the outcome. Aim was to derive a prognostic model in patients of ACLF by APASL deÞnition.

Methods: Total 1021 ACLF cases with 90 days follow up enrolled into the APASL ACLF Research Consortium (AARC) were analyzed. A derivation set of 338 cases analyzed for a prognostic model and calibrated in 683 cases validation set.

Results: Of all the baseline independent predictor of mortality, total bilirubin, Creatinine, Lactate, INR and hepatic encephalopathy were considered. AUROC in derivation and validation cohort were 0.797 and 0.793 respectively. AARC ACLF score was developed with a minimum and maximum of 5 and 15. The score was better than the MELD and CLIF SOFA with an AUROC of 0.76, sensitivity 70 %, speciÞcity 67 %, PPV 78 % and NPV of 58 % in predicting 90 days survival. Grading was done with Grade A (5Ð9), Grade B (10Ð11) and Grade C (12Ð15 points). The mortality risk increases by 9.7 % with each unit increase. Score of 11 at baseline or persistence of the same in Þrst week associated with 100 % mortality in 30 days. Overall median survival was 26.3 days and that of Grade B, C being 16 and 5 days respectively and overall survival of 51.8 %.

Conclusion: The AARC ACLF score is dynamic, simple and better to the existing models. The deÞnitive therapies i.e. transplant can be predicted within Þrst week.

 

COMPARISON OF THE ACUTE ON CHRONIC LIVER FAILURE SEVERITY SCORE: A NEED FOR SIMPLE AND DYNAMIC ONE

Priyanka Jain1, Ashok K. Choudhury2, Mamun A. Mahtab3, Yogesh K. Chawla4, Soek S. Tan5, Harshad Devarbhavi6, Saeed S. Hamid7, C. E. Eapen8, Hasmik Ghazinyan9, Zhongping Duan10, Ajit Sood11, Guan H. Lee12, A. K. Dokmeci13, Laurentius A. Lesmana14, Diana A. Payawal15, Rakhi Maiwall16, Manoj K. Sharma17, Guresh Kumar18, Shiv K. Sarin19,AARC Group20  1Institute of Liver and Biliary Sciences, New Delhi, India; 2Institute of Liver and Biliary Sciences, New Delhi, India; 3Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 4PGIMER, Chandigarh, India; 5Selayang Hospital University of Malaya, Kuala Lumpur, Malaysia; 6St John Medical College, Bangalore, India; 7Aga Khan University Hospital, Karachi, Pakistan; 8C M C, Vellore, India; 9Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia; 10Beijing Youan Hospital, Capital Medical University, Beijing, China; 11CMC, Ludhiana, India; 12Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 13Ankara University School of Medicine, Ankara, Turkey; 14Digestive Disease and Oncology Centers, Medistra Hospital, Jakarta, Indonesia; 15Fatima Medical University Hospital, Valenzuela Metro Manila, Philippines; 16Institute of Liver and Biliary Sciences, New Delhi, India; 17Institute of Liver and Biliary Sciences, New Delhi, India; 18Institute of Liver and Biliary Sciences, New Delhi, India; 19Institute of Liver and Biliary Sciences, New Delhi, India; 20APASL ACLF Working Group

Background and aim: Acute on chronic liver failure is rapidly progressive liver failure with high short term mortality. A simple and dynamic prognostic model is needed for early and deÞnitive therapy. Aim was to compare the existing disease severity scores for predic-tion of 90 days survival in ACLF patients by APASL deÞnition Method: 1021 ACLF patientsÕ enrolled into the APASL ACLF Research Consortium (AARC) were analyzed. CTP, MELD, SOFA, CLIF SOFA, APACHE II and number of organ failure at baseline and delta change on D4 and D7 were compared with the new onset HE or AKI, change in lactate or bilirubin for prediction of 90 days mortality.

Results: The baseline MELD, CLIF SOFA, APACHE II, SOFA, CTP and number of organ failure as mortality predictor had AUROC of 0.74, 0.72, 0.71, 0.71, 0.68 and 0.68, respectively. Their delta change at D4 or D7 were poor predictor of outcome with AUROC\0.68. The new onset AKI [HR: 2.58 (1.76Ð3.75)], increase in total bilirubin by 6.1 mg/dl [HR: 2.16 (1.77Ð2.61)], new onset HE [HR: 2.14 (1.36Ð3.34)], increase in lactate by 1.48 meq/l [HR: 1.85 (1.45Ð2.34)] on D4 and D7 had a better hazard for mortality than SOFA [HR: 2.13 (1.41Ð3.20)], MELD [HR: 1.63 (1.33Ð1.99)], CLIF-SOFA [HR: 1.42 (1.06Ð1.90)], CTP [HR: 1.35 (1.07Ð1.69)] and APACHE II [HR: 1.81 (1.65Ð2.22)] change.

Conclusion: The existing disease severity score were poor predictor of outcome and lack dynamicity. The change in bilirubin, lactate with development HE and/or AKI were good predictors. A model considering above is strongly recommended.

 

LIVER TRANSPLANTATION FOR PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE IN ASIA

Guan-Huei Lee1,2, Thandar Tun1, Seng-Gee Lim1,2, Ashok Choudhury3, Saeed Hamid4, Zaigham Abbas5, Deepak Amarapurkar6, Yogesh K. Chawla7, A. Kadir Dokmeci8, Hasmik Ghazinyan9, Dong Jong Kim10, Soek Siam Tan11, Qin Ning12, Laurentius A. Lesmana13, Mamun Mahtab14, Piyawat Komolmit15, M. F. Yuen16, Osamu Yokosuka17, Richard Moreau18, Shiv K. Sarin3,19  1Department of Medicine, National University Health System, Singapore, Singapore; 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; 3Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India; 4Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan; 5Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan; 6Department of Gastroenterology and Hepatology, Bombay Hospital and Medical Research, Mumbai, India; 7Post Graduate Institute of Medical Education and Research, Chandigarh, India; 8Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey; 9Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia; 10Center for Liver and Digestive Diseases, Hallym University Medical Center, Gangwon-do, Republic of Korea; 11Department of Gastroenterology and Hepatology, Selayang Hospital, Selayang, Malaysia; 12Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 13Department of Hepatology, Medistra Hospital, Jakarta, Indonesia; 14Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 15Division of Gastroenterology and Hepatology, Department of Medicine, Chulalongkorn University, Bangkok, Thailand; 16Department of Medicine, The University of Hong Kong, Hong Kong, China; 17Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan; 18Hepatology Service, Hospital Beaujon, Assistance Publique-Hopitaux de Paris, Clichy, France; 19APASL ACLF Working Party

Aim: Acute-on-chronic liver failure (ACLF) is characterized by high mortality. Liver transplantation (LT) is effective in patients who do not improve with supportive measures. This study examines the outcome of ACLF patients who underwent LT in Asia.

Methods: Prospectively collected data from 17 Asian countries in the APASL ACLF Research Consortium was analyzed. 43 patients who underwent LT for ACLF were compared with 1657 non-transplanted ACLF patients. The variables analyzed include patient demographics, acute insult, background liver disease, severity scores (MELD and SOFA scores) and post-LT outcome.

Results: Mean age of LT patients was 42.1 years and non-trans-planted patients was 43.7 years. 74.4 % of LT patients and 85.1 % of non-LT patients were male. The most common acute liver insult was HBV reactivation (24.4 %) in LT patients, compared with alcohol (49.5 %) in non-LT patients. Three-month survival rate was 76.7 % in LT group, and 52.6 % in non-LT group. Mean MELD scores prior to transplant was (27.7 ± 4.7) and (30.5 ± 8.3) in non-transplant group. In LT patients, baseline renal dysfunction predicted mortality (mean urea: 1.4 vs. 0.84 mg/dL, p = 0.015) (mean creatinine: 61 vs. 27 lmol/l, p = 0.042). High SOFA score was signiÞcantly associated with mortality in both LT (12.5 vs. 8, P = 0.015) and non-LT (8.3 vs. 10.9, p \ 0.001) patients. In non-LT patients, baseline urea (68.5 vs. 41.2 lmol/l, p \ 0.001), MELD (33.8 vs. 27.5, p \ 0.001) and Child-Pugh score (12 vs. 11, p \ 0.001) were independently associated with mortality.

Conclusion: Baseline renal dysfunction and higher SOFA score predict poorer LT outcome in ACLF patients

2017 AASLD ACLF STC

Acute on Chronic Liver Failure (ACLF) has a better long-term survival than Acute decompensation- a study of 4897 patients from APASL ACLF Research Consortium (AARC) with a follow-up of 5 years.

Authors: A. Choudhury7; H. Devarbhavi12; Z. Duan4; C. Yu4; Q. Ning5; K. Ma5; S. Hamid13; A.

Butt13; W. Jafri13; C. Eapen21; A. Goel21; S. Tan26; Y. Chawla15; S. Taneja15; M. Al Mahtab3; S.

Treeprasertsuk19; D. Kim11; G. Lee22; S. Lim22; L. Lesmana8; R. Lesmana8; H. Ghazinian10; P.

Rao2; Z. Abbas1; D. Amarapurkar25; J. Sollano17; G. Carpio17; D. Payawal20; M. Sahu9; S.

Shah18; C. Kalal18; G. Lau16; M. Yuen24; M. Karim6; A. Dokmeci23; V. Prasad14; P. Jain7; I.

Paulson7; G. Kumar7; S. Sarin7; A. Working Party7

Institution(s): Ziauddin University Hospital1; Asian Institute of Gastroenterology2; Bangabandhu Sheikh Mujib Medical University3; Beijing You’an Hospital4; Tongji Hospital, Tongji Medical College5; Sir Salimullah Medical College, Mitford Hospital6; ILBS7; Medistra Hospital8; IMS &SUM Hospital9; Nork Clinical Hospital of Infectious Disease10; Hallym University College of Medicine11; St John Medical College12; Aga Khan University13; VGM Hospital14; PGIMER15; Humanity and Health Medical Group16; University of Santo Tomas17; Global Hospital18; Chulalongkorn University19; Cardinal Santos Medical Center20; CMC Vellore21; Yong Loo Lin School of Medicine22; Ankara University School of Medicine23; Queen Mary Hospital24; Bombay Hospital & Medical Research Center25; Hospital Selayang26

Background and Aims: - ACLF is a distinct entity with high short-term mortality due to severity of acute insult and rapid worsening of liver failure. It is not known whether patients surviving acute insult have a better long-term survival than those with decompensated cirrhosis.  We studied the survival of ACLF patients beyond 90 days and compared with acute decompensation of previously decompensated cirrhosis.

Patients and Methods: Patients of cirrhosis with acute decompensation (within last 3 months) in presence of prior decompensation were compared with patients of ACLF for the survival outcome beyond 90 days. Patient from 40 centres across Asia from AARC cohort, since october 2012 to october 2016 were analyzed.

Results: ACLF (n=2743) and AD (2154) at enrolment were followed for 90 days, 1833 ACLF, and 1868 AD, were followed up to 5 years, with a median follow up of 14737 and 12904 person months respectively. At presentation, ACLF patients were younger (49.69±10.86 vs. 47.23±11.67 yr, p<0.001) with higher alcoholic hepatitis (29.5% vs. 8.7% , p<0.001), HBV reactivation (7.9% vs.2.3%, p<0.001), DILI (8.3% vs. 4.3%, p<0.001) as an acute insult and less of chronic insult like NASH (14.1% vs. 10.2%, p<0.001), HCV (10% vs. 6.1%, p<0.001) but of a higher HBV related CLD (13.9% vs. 7.3%). The ACLF patients had significantly higher total bilirubin, INR, serum creatinine and severity scores and lower Hb, platelet, serum albumin and sodium (p<0.001) in addition to raised AST and ALT (p<0.001) at baseline {table-1} as well as high disease severity score (MELD 33.2±13.7 Vs. 23.9±11.3, p<0.001). The 90 day survival [HR: 0.73(0.66-0.82), p<0.01] as well as follow up for 5 years [HR: 0.79(0.72-0.87), p<0.001] had lower cumulative survival with diagnosis of ACLF in comparison to AD {fig-2}. The high short-term (90days) mortality in ACLF 33.2% (910/2743) and23% (496/2154) (p<0.001) than AD and also at 6 months (35.2 vs. 24.9%), 12 months (37% vs. 26.8%) and 24 months (38.9% vs. 29.3%) but not beyond 24 months till 5 year follow up. But upon subgroup analysis with respect to time i.e. after 24 months of index presentation with ACLF the survival is worse in AD cohort [HR: 1.94(1.17-2.21), p<0.01] {fig-1}

Conclusion: ACLF as per APASL in absence of prior decompensation with cirrhosis or non-cirrhotic chronic injury and on subject to an acute hepatic insult had higher 90 days mortality due to severity of acute insult. Among the survivors at 90 days the hepatic reserve showed an improvement and beyond 2 years from index insult the survival is much better.

 

 

Table-1

 

 

AD (n=2154)

ACLF (n=2743)

p

Age in years

49.69±10.86

47.23±11.67

<0.001

Gender: Male (n,%)

1796(83.4)

2327(84.8)

0.17

Acute Etiology

 

 

 

Alcoholic hepatitis (n,%)

187(8.7)

809(29.5)

<0.001

Acute Viral hepatitis (n,%)

405(18.9)

523(19.1)

0.57

HBV reactivation (n,%)

50(2.3)

217(7.9)

<0.001

Drug Induced (n,%)

93(4.3)

227(8.3)

<0.001

Unknown (n,%)

83(3.9)

112(4.1)

0.68

Chronic etiology

 

 

 

Alcohol (n,%)

1088(50.5)

1407(52.2)

0.58

NASH (n,%)

303(14.1)

274(10.2)

<0.001

HCV (n,%)

215(10)

164(6.1)

<0.001

HBV (n,%)

157(7.3)

374(13.9)

<0.001

AIH (n,%)

51(2.4)

71(2.6)

0.62

Cryptogenic (n,%)

293(13.6)

346(12.8)

0.31

Lab Parameter

 

 

 

Hb (mean±SD)

10.12±2.26

10.41±2.29

<0.001

Total WBC count (range)

7.5(0.5,150)

9.5(1,95)

<0.001

Platelet count (range)

 

 

 

Total Bilirubin (mean±SD)

6.02±7.34

14.06±11.91

<0.001

AST/SGOT (range)

63(10,4910)

99(6.3,7552)

<0.001

ALT/SGPT (range)

34(3,4343)

44(0.1,4742)

<0.001

Serum Albumin (mean±SD)

2.50±0.63

2.34±0.63

<0.001

PT-INR (mean±SD)

1.79±0.83

2.15±1.06

<0.001

Serum creatinine (range)

0.9(0,12.7)

1(0,15.3)

<0.001

Serum Sodium (mean±SD)

133.34±6.84

131.65±7.39

<0.001

Disease severity

 

 

 

CTP (mean±SD)

9.95±2.09

10.85±2.00

<0.001

MELD (mean±SD)

23.94±11.34

33.17±13.74

<0.001

MELD Na (mean±SD)

26.18±10.23

34.17±11.59

<0.001

Liver transplant (n,%)

68(3.2)

71(4.7)

0.02

Cumulative Mortality

 

 

 

6 months (n,%)

537(24.9)

967(35.2)

<0.001

12 months (n,%)

578(26.8)

1014(37)

2 years (n,%)

632(29.3)

1066(38.9)

5 years (n,%)

671(31.2)

1088(39.7)

 

 

 

Fig-1

 

 

 

 

 

 

 

Fig-2

 

 

 

 

Impact of acute and chronic insults on 90 days outcome and complications in patients with Acute on Chronic Liver Failure (ACLF)- study of 2714 patients from APASL ACLF Research Consortium (AARC)

Authors: I. Paulson30; A. Choudhury30; M. Al Mahtab27; H. Devarbhavi16; Z. Duan28; C. Yu28;

Q. Ning17; K. Ma17; C. Eapen13; A. Goel13; Y. Chawla2; S. Taneja2; S. Hamid3; A. Butt3; W.

Jafri3; D. Kim8; S. Tan10; D. Amarapurkar29; J. Hu14; H. Ghazinian15; L. Lesmana21; R.

Lesmana21; A. Shukla4; G. Lee12; S. Lim12; S. Shah18; C. Kalal18; M. Sahul1; Z. Abbas20; S.

Treeprasertsuk26; M. Karim23; G. Lau11; P. Rao7; D. Payawal19; V. Saraswat5; J. Sollano9; G.

Carpio9; M. Yuen24; V. Prasad22; A. Dokmeci25; O. Yokosuka6; P. Jain31; G. Kumar31; S.

Sarin31; A. group31

Institution(s): IMS &SUM Hospital1; PGIMER2; Aga Khan University3; KEM Hospital and Seth

GSMC4; SGPGI5; Chiba University6; Asian Institute of Gastroenterology7; Hallym University

College8; University of Santo Tomas9; Hospital Selayang10; Humanity and Health Medical

Group11; Yong Loo Lin School of Medicine12; CMC Vellore13; 302 Millitary Hospital14; Nork

Clinical Hospital of Infectious Disease15; St John Medical College16; Tongji Hospital17; Global

Hospital18; Cardinal Santos Medical Center19; Ziauddin University Hospital20; Medistra

Hospital21; VGM Hospital22; Sir Salimullah Medical College23, Mitford Hospital; Queen Mary

Hospital24; Ankara University School of Medicine25; Chulalongkorn University26; Bangabandhu

Sheikh Mujib Medical University27; Beijing You’an Hospital28; Bombay Hospital & Medical

Research Center29; ILBS30 stratify the risk of mortality in ACLF patients.

Background and Aims: Acute on Chronic Liver Failure (ACLF) is distinct syndrome with high short term mortality due to an acute hepatic insult leading to liver failure and subsequent extra-hepatic organ failure in a patient with chronic liver disease. The type of insult, severity of liver disease is crucial for defining the outcome, hence the therapy. The present study aims to identify the etiologies for various acute and chronic insult and their impact on 90days survival and complications.

Methods: 2714 ACLF (APASL definition) patients were enrolled from 30 centers across Asia into AARC database from October 2012 to June 2017were analyzed for the various acute and chronic insult. The impact of etiology on disease severity, complications, organ failures and 90 days survival were analyzed.

Results: In 2714 patients, mean age was 44.5±12.6 and male predominance was seen (85.1%) with respect to female (14.6%). Predominant acute insults was severe alcoholic hepatitis (SAH) (1251,45.7%) followed by Hepatitis B(555,20.3%), Drug induced (251,9.2%,) acute viral hepatitis (251,9.2%), Autoimmunue flare (57,2.1%,0.52) and (349,12.8%) of unknown etiology. The various causes for  chronic liver disease were Alcohol(1332,48.7%), HBV (687,25.1%), HCV (52,1.9%), Autoimmune hepatitis(81,3%), (540,19.7%) cryptogenic or NASH. Drug induced liver injury (DILI) as an acute insult (HR=1.89, 95 CI 1.29-2.74, p<0.001) and presence of  Hepatic encephalopathy (HR=2.19,95CI 1.63-2.95,p<0.001) and Acute Kidney Injury (HR=2.68, 95CI 2.01-3.57, p<0.001) independntly increases the 90 days mortality. Among the complications of ACLF at presentation, HE (HR=2.09,95CI 1.31-3.36,p<0.01) and variceal bleed (HR=2.24. 95CI 0.99-5.02,p<0.05) were frequently obsreved with drug as acute insult and AIH related CLD showed a significant association with HE(HR=1.34, 95 CI 0.12-0.92,p<0.03). Organ failure at presentation was  very often seen in severe alcoholic hepatitis (3.3,2.32-4.69,<0.001) followed by HBV (3.19,1.89-5.39,<0.001) and DILI (2.29,1.17-4.50,p<0.02). Similarly alcohol (3.39,2.37-4.84,<0.001) and HBV (3.00,1.86-4.84,<0.001) related CLD were associated with higher incidence of organ failure. The 90 days mortality with acute insult was highest with AIH flare (23/57,57%) followed by drug induced (139/251,55.5%) and was lowest for acute viral hepatitis (86/251, 34.3%). Similarly the mortality was highest among the cryptogenic CLD (254/540, 47.04%) followed by HCV (24/52,46.15%)

Conclusions: Our results show that  alcohol is the commonest  acute insult as well as chronic liver disease in the Asian cohort and is associated with higher risk of organ failure  The AARC data shows that etiology predicts organ falure;  drug induced liver injury and autoimunue flare are assocaited with AKI and HE and predict 90 day mortality.

 

 

Acute-On-Chronic Liver Failure In Wilson’s Disease - A Series Of 38 Cases From Apasl-Aclf Research Consortium (AARC)

Authors: P. Gupta10; C. Eapen10; A. Goel10; A. Choudhury5; S. Tan7; G. Lee1; H. Devarbhavi4; Y. Chawla6; S. Taneja6; Z. Duan2; C. Yu2; A. Shukla9; P. Rao3; Z. Abbas8; P. Jain5; I. Paulson5; S. Sarin5; A. group5

Institution(s): Yong Loo Lin School of Medicine1; Beijing You’an Hospital2; Asian Institute of Gastroenterology Hyderabad3; St. John Medical College4; ILBS5; PGIMER6; Hospital Selayang7; Ziauddin University Hospital8; KEM Hospital and Seth GSMC9; Christian Medical College10

Background: Acute on Chronic Liver Failure (ACLF) is a distinct syndrome with high short-term mortality due to an acute hepatic insult leading to liver failure and subsequent extra-hepatic organ failure in a patient with chronic liver disease. Wilson’s disease flare in a back ground of the chronic disease may result in the syndrome of ACLF, but the data is sparse on this aspect. We analyzed Wilson’s disease presenting as ACLF from the AARC data base.

Methods: 38 cases with Wilson’s disease, presented with ACLF (APASL definition) were recruited from March 2012 to July 2017. Data was obtained from multiple centres and aggregated on a common platform of AARC. Baseline parameters and further inhospital course were followed til 90 days for death or liver transplant.

Results: Wilson disease constite 1.3%(36 of 2732) of ACLF. 14 ACLF cases with underlying Wilson’s disease had defined acute etiological insult (Group-A) and were aged 34.9±22.1 with 11 males. in group-B. In rest of the 24 cases the etiology of the acute insult could not be defined (Group-B). They were aged 29.5±14.6 years with 14 males. All cases had index presentation as ACLF and were diagnosed as having Wilson’s disease subsequently. The etiology of acute insult was acute viral hepatitis in 7 cases (Hepatitis E in 3, Hepatitis A in 3, Epstein Barr Virus in 1 case), drug induced liver injury in 5 cases (3 were on anti-tuberculosis therapy), sepsis and ethanol in 1 case each. 20 cases (8 in Group-A) had hepatic encephalopathy (HE) at base line and 2 developed HE on day 4 (both from Group-A). The duration of jaundice was 63.9±31 days with all patients having ascites at baseline. Median hospital stay was 24 (range 9-64) and 9 (range 1-36) days p<0. 001.The ALP to-bilirubin ratio

of < 4 was observed in 9 cases (24%) whereas AST-to-ALT ratio was> 2.2 in 17 cases (45%). The in-hospital mortality was (7/14) 50% for Group-A cases which was better than (16/22) 73% for Group-B cases, while 2 in Group B underwent liver transplant. The mortality with diagnosis of ACLF is higher (63.9%) against the overall mortality (43.8%) in AARC cohort due to ACLF [HR: 1.83, 95CI%, 1.22-2.74,p =0.003].The mortality was(8/ 14) 57% for Group-A cases which was better than(16 / 22) 73% for Group-B cases (p<0.01), while 2 in Group B underwent liver transplant.

Conclusion: This prospective dataset is the largest series of Wilson’s disease presenting as ACLF. Wilson’s disease patients have a higher mortality with diagnosis of ACLF and is much higher in absence of an identifiable precipitant for the same. This distinct syndrome needs new and early interventional strategies.

Disclosure: Nothing to disclose.

 

Validation of AARC scores to predict short term mortality in patient of Acute on Chronic Liver Failure

Authors: P. Jain; A. Choudhury; M. Al Mahtab8; H. Devarbhavi5; Z. Duan24; C. Yu24; Q.

Ning13; K. Ma13; C. Eapen12; A. Goel12; Y. Chawla18; S. Taneja18; S. Hamid20; A. Butt20; W.

Jafri20; S. Tan6; D. Kim4; H. Ghazinian26; D. Amarapurkar15; S. Treeprasertsuk23; J. Hu30; L.

Lesmana10; R. Lesmana10; G. Lee17; S. Lim17; A. Shukla22; S. Shah28; C. Kalal28; M. Sahu27; Z.

Abbas1; J. Sollano29; G. Carpio29; G. Lau9; M. Karim11; P. Rao21; D. Payawal7; A. Dokmeci25;

V. Saraswat14; M. Yuen2; V. Prasad19; O. Yokosuka3; I. Paulson16; G. Kumar16; S. Sarin16; A.

group16

Institution(s): Ziauddin University Hospital1; Queen Mary Hospital2; Chiba University3; Hallym

University College of Medicine4; St John Medical College5; Hospital Selayang6; Cardinal

Santos Medical Center7; Bangabandhu Sheikh Mujib Medical University8; Humanity and

Health Medical Group9; Medistra Hospital10; Sir Salimullah Medical College, Mitford Hospital11;

Christian Medical College12; Tongji Hospital13; SGPGI14; Bombay Hospital & Medical Research

Center15; ILBS16; Yong Loo Lin School of Medicine17; PGIMER18; VGM Hospital19; Aga Khan

University20; Asian Institute of Gastroenterology Hyderabad21; KEM Hospital and Seth

GSMC22; Chulalongkorn University23; Beijing You’an Hospital24; Ankara University School of

Medicine25; Nork Clinical Hospital of Infectious Disease26; IMS &SUM Hospital27; Global

Hospital28; University of Santo Tomas29; 302 Military Hospital Beijing30

Background and Aim: Acute on chronic liver failure is rapidly progressive liver failure and is associated with a significant rate of mortality within 28 days. A simple and dynamic prognostic model is needed for early prognostication and listing for liver transplantation. This study was undertaken to validate a previously derived AARC score based on a prospective cohort of 1402 ACLF patients and to compare the AARC score with existing models in the new cohort.

Methods: 1494 ACLF patients were enrolled across 30 centers from Oct 2012 to Jan 2017 in Asia Pacific into APASL ACLF research consortium (AARC) for analysis. The AARC score [range 5-15] is based on five independent predictors of 28 days mortality; total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy [table1]. We validated AARC score on this cohort and compared it with existing prognostic models using AUROC.

Results: Of the 1494 enrolled patients, the 28 day survival was 71%. The AUROC of AARC score in this validation cohort was 0.77 with 75% sensitivity, 65% specificity, 45.4%PPV and 88.4% NPV respectively. The validated AARC score was comparable (p=0.086) with previous cohort (N=1402) of derived AARC score. It was found that AUROC of the validated AARC score (0.77) was significantly (p<0.001) higher than other CTP, MELD, SOFA, CLIF SOFA, APACHEE score with AUROC 0.64,0.71, 0.72, 0.72, 0.74 in predicting 28 day mortality. The new validated AARC score was categorized into grade [I:5-7, II: 8-10, III:11-15 points] having cumulative mortality of 7.2%, 22.3% and 60.9% respectively [ Fig 2]. A score of 9 was seen consistently same in the first week among survivors, where as a score of >10 was observed same in one week and increased exponentially at day15 among non survivors (p=0.001, GEE model) [fig1]

Conclusions: AARC score is useful scoring systems to provide information on short term mortality in ACLF patients according to APASL definition. Moreover it is superior to the existing prediction models and also predicts the need for intervention.

 

 

Validated AARC score vs CLIF SOFA

0.77 (0.71-0.80) vs 0.72(0.67-0.77,

p <0.001

Validated AARC score vs SOFA

0.76(0.71-0.80) vs 0.70 (0.65-0.75),

p<0.001

Validated AARC score vs MELD

0.77(0.74-0.80) vs 0.73(0.69-0.77),

p<0.001

Validated AARC score vs APACHEE

0.77(0.73-0.82) vs 0.73(0.68-0.78),

p=0.01

 

 

 

 

 

                                                                

Disease severity score

AUROC

Cut off

Sensitivity

Specificity

PPV

NPV

Validated AARC score

0.77

09.6

75.0

65.0

45.4

88.4

CTP

0.64

12.5

68.0

54.0

41.3

79.1

MELD

0.71

29.7

67.3

66.4

47.0

84.1

SOFA

0.72

08.5

70.0

60.0

55.0

77.5

Apache

0.74

16.5

68.0

69.0

58.0

75.0

CLIFSOFA

0.72

11.5

68.6

66.0

54.8

75.7

 

 

 

 

Univariate

Multivariate

 

Parameter

HR

95CI

P

HR

95CI

P

Hb (gm/dl)

1.02

1.00-1.21

0.04

 

 

 

Total WBCs Count

1.94

1.74-2.16

0.03

 

 

 

PT-INR

3.92

3.37-4.55

<0.001

1.90

1.60-2.25

<0.001

Urea (mg/ml)

1.70

1.58-1.84

0.02

 

 

 

S Creatinine (mg/ml)

2.37

2.16-2.60

<0.001

1.88

1.69-2.09

<0.001

Total Bilirubin (mg/dl)

1.78

1.58-2.00

<0.001

1.65

1.45-1.88

<0.001

Lactate (mmol/ml)

2.52

2.28-2.78

<0.001

2.09

1.85-2.35

<0.001

Hepatic Encephalopathy (present/absent)

3.35

2.91-3.87

<0.001

2.27

1.95-2.65

<0.001

               

 

 

 

 

Hepatitis E And Acute On Chronic Liver Failure: Outcome And Predictors Of Mortality In Asia Pacific Region

Authors: A. Butt13; S. Hamid13; A. Choudhury10; W. Jafri13; Y. Chawla5; S. Taneja5; Z. Abbas4; A. Shukla16; M. Mahtab11; D. Amarapurkar9; M. Karim17; C. Eapen1; A. Goel1; H. Ghaziniyan19; P. Rao6; M. Sahu8; S. Shah14; C. Kalal14; H. Devarbhavi12; Z. Duan7; C. Yu7; S. Tan15; D. Payawa2l; O. Yokosuka3; P. Jain10; I. Paulson10; S. Sarin10; A. AARC18

Institution(s): Christian Medical College1; Cardinal Santos Medical Center2; Chiba University3;

Ziauddin University Hospital4; PGIMER5; Asian Institute of Gastroenterology6; Beijing You’an

Hospital, Capital Medical University7; IMS &SUM Hospital8; Bombay Hospital & Medical

Research Centre9; Institute of Liver and Biliary Sciences10; Bangabandhu Sheikh Mujib Medical

University11; St John Medical College12; Aga Khan University Hospital13; Global Hospital14;

Hospital Selayang15; KEM Hospital and Seth GSMC16; Sir Salimullah Medical College, Mitford

Hospital17; AARC APASL Working Party18; Nork Clinical Hospital of Infectious Disease19

Background: One of the distinctive factors that could lead to acute on chronic liver failure is

acute hepatitis E (HEV). However, most of available data carries the limitation of smaller

sample size or center based experiences. Herne, the current study aims to analyze the

APASL-ACLF research consortium (AARC) database to evaluate the clinical and biochemical

profile, predicting factors of 90 days mortality and to compare the various existing prognostic

models for predicting 90 days mortality in patients with ACLF triggered by acute hepatitis E

infection.

Methods: APASL-ACLF research consortium (AARC), consisting of 24 tertiary centers across Asia-Pacific regions, maintains an online database for patients diagnosed to have ACLF according to APASL criteria. All patients who had ACLF with acute hepatitis E were reviewed for the current study.

Results: Out of 2897 patients with ACLF 230 (7.9%) had acute deterioration due to HEV. Mean age was 48.29±13.50 years and 83.9% were male. The most common cause of chronic liver disease was alcohol (26.5%) followed by cryptogenic cirrhosis (25.7%) and NASH (25.7%). Overall 64.8% patients survived at day 90. Liver transplantation was done in 4.3% cases. On univariate analysis presence of PSE, AKI on presentation, serum ureae, creatinine,  total bilirubin, INR, lactate, CTP, MELD, MELD Na, SOFA, CLIF-SOFA, AARC score were the factors associated with mortality. However, on multivariate analysis presence of PSE, SOFA, AARC score at base line were the factors associated with mortality. When we compared various prognostic models MELD and AARC scores were found to have higher accuracy.

Conclusion: Acute hepatitis E is one of the leading causes of ACLF in Asia pacific region and associated with high mortality without liver transplantation. Presence of PSE, SOFA, AARC score at base line were the factors associated with 90 days mortality. Among prognostic models MELD and AARC scores were found to have higher accuracy.

Reference(s):

Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, Chawla YK, Dokmeci  AK, Garg H, Ghazinyan H, Hamid S. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatology international. 2014 Oct 1;8(4):453-71.

Disclosure: Nothing to disclose.

 

 

2017 AASLD

Prevalence, spectrum, predictors and outcome of infections in patients with Acute on Chronic

Liver Failure

Lovkesh Anand1, Ashok K. Choudhury1, Irene Paulson1,Barjesh C. Sharma1, Manoj Kumar1, Vikram Bhatia1, Ankur Jindal1,Kapil D. Jamwal1, Rakhi Maiwall1, Saggere M. Shasthry1,Vikas Khillan1, Guresh Kumar1, Harshad Devarbhavi2,Soek Siam Tan3, CE Eapen4, Ashish Goel4, Jinhua Hu5,Deepak N. Amarapurkar6, Saeed S. Hamid7, Amna S. Butt7,Syed M. Jafri7, Zhongping Duan8, Yu Chen8, Samir R. Shah9,Guan Huei Lee10, Laurentius A. Lesmana11, Yogesh K. Chawla12,Sunil Taneja12, Zaigham Abbas13, Padaki Nagaraja Rao14,Akash Shukla15, Jose D. Sollano16, Gian Carpio16, Hasmik Ghazinyan17, Diana A. Payawal18, Abdulkadir Dokmeci19,George Lau20, Shiv K. Sarin1, APASL ACLF Working Party21;APASL working party; 1Institute of liver and biliary sciences,New Delhi, India; 2St John’s Medical College, Banglore, India;3Selayang Hospital, Kepong, Malaysia; 4Christian Medical College,Vellore, India; 5302 militiary Hospital, Beijing, China;6Bombay Hospital, Mumbai, India; 7Aga Khan University, Karachi,Pakistan; 8Beijing Youan Hospital, Beijing, China; 9GlobalHospital, Mumbai, India; 10National University of Health System, Singapore, Singapore; 11Medistra Hospital, Jakarta,

Indonesia; 12PGIMER, Chandigarh, India; 13Ziauddin University,Karachi, Pakistan; 14Asian Institute of gastroentrology,Hydrabad, India; 15Kem Hospital, Mumbai, India; 16University of Santos Tomas, Manila, Philippines; 17Nork Clinical Hospital,Yerevan, Armenia; 18Cardinal Santos Medical Center, Manila,

Philippines; 19Ankara University, Ankara, Turkey; 20Humanity and Health Medical Group, China, China; 21APASL WorkingParty, New Delhi, India

Background and Aims: In Acute on Chronic Liver Failure (ACLF), continued injury and persistent inflammation and subsequent immunoparalysis predisposes to a perpetuating cascade and high incidence of infections. Therefore, the spectrum and source of infection and sepsis is likely to be different in ACLF patients. We investigated the prevalence, microbiological spectrum, predictors andoutcome of infections in a large cohort of ACLF patients

from Asia.

Methods: 2,825 ACLF patients recruited prospectively between 2012-2017 upto 90 days for onset of sepsis or death or liver transplant. Standard terminologies were used to define Pneumonia, Urinary Tract Infection(UTI), Spontaneous Bacterial Peritonitis(SBP), Spontaneous Bacterial Empyema(SBE), Spontaneous bacteremia(SB), Fungemia, skin and soft tissue infections(SSTI).

Results: Overall, 845(29.9%) patients had sepsis, of which 183(21.7%, Gr.A) had infections only at presentation, 454(53.7%, Gr.B) nosocomial and 208(24.6%, Gr.C) had second-hit sepsis. UTI(35.9%), pneumonia(26.3%), SBP(19.2%) and SB(13.4%) were common infections with small contribution by SSTI(1.4%) and SBE(1.05%). 30.7% of pneumonia and 71.4% of SBP and SBE were culture negative. Common bacteria identified for UTI were E.Coli(44.9%) and enterococcus(25.1%); for pneumonia, Klebsiella(15.8%) and methicillin resistant staphylococcus(MRSA;5.7%); for SBP and SBE, E.coli (10.9%,21.4%) and MDR klebsiella (7.3%,14.2%) and for SB, E.coli(25.9%), Klebsiella(20.3%), MRSA(16.1%) and enterococcus(15.4%).Fungal pneumonia (aspergillus) was seen in 27.2%, candidia in UTI in 14.2%, fungemia in 2.5% and fungal SBP in 3% patients; 89.7% fungal infections had associated bacterial infections. Predictors of mortality included bacteremia[2.6 (1.81-3.74)], fungal infections [2.33(1.63- 3.32)] and pneumonia [2.6(1.93-3.50)]. Survival was lowest in Group C <B< A (median survival A:B:C – 49:45:18 days, p=0.003). Alcoholic hepatitis (AH)[2.01(1.49-2.71), p<0.001] and DILI [1.86(1.26-2.74), p=0.002] were independent predictors of sepsis compared to other etiologies. Low albumin [0.58(0.49-0.68), p<0.001] and high MELD score [1.4(1.3-1.5), p<0.001] also significantly predicted sepsis in MV analysis.

Conclusions: The risk of infection is significantly increased with low serum albumin, high MELD and with AH and DILI as acute insult in ACLF patients. Fungal infections alone or with bacterial infections and second hit sepsis result in poorer clinical outcome. Maintaining near normal serum albumin along with emperical antibiotics (for Klebsiella and E.coli) and low threshold for antifungals (in select cases) is recommended to prevent sepsis and improve survival in ACLF patients.

 

 

Flare of Autoimmune Hepatitis as a cause of acute on chronic liver failure and its response to steroid therapy

Lovkesh Anand1, Ashok K. Choudhury1, Chhagan Bihari1, Barjesh C. Sharma1, Manoj Kumar1, Vikram Bhatia1, Ankur Jindal1, Kapil D. Jamwal1, Rakhi Maiwall1, Saggere M. Shasthry1, Guresh Kumar1, Priyanka Jain1, Soek Siam Tan2, Samir R. Shah3, Saeed S. Hamid4, Amna S. Butt4, Syed M. Jafri4,Deepak N. Amarapurkar5, Yogesh K. Chawla6, Sunil Taneja6, Mamun A. Mahtab7, Hasmik Ghazinyan8, Zhongping Duan9,Yu Chen9, Akash Shukla10, Jinhua Hu11, Zaigham Abbas12, Sombat Treeprasertsuk13, Laurentius A. Lesmana14, Jose D. Sollano15, Gian Carpio15, Manoj K. Sahu16, Shiv K. Sarin1; APASL ACLF working party;

1Institute of liver and biliary sciences,New Delhi, India; 2Hepatology, Selayang Hospital, Kepong, Malaysia; 3Hepatology, Global Hospital, Mumbai, India; 4Medicine,Aga Khan University, Karachi, Pakistan; 5Gastroenterology, Bombay Hospital, Mumbai, India; 6PGIMER, Chandigarh,India; 7Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 8Nork Clinical Hospital, Yerevan, Armenia; 9Hepatology, Youan Hospital, Capital Medical University, Beijing,China; 10Kem Hospital, Mumbai, India; 11302 Hospital, Beijing, China; 12Ziauddin University, Karachi, Pakistan; 13Chulalongkorn University, Bangkok, Thailand; 14Medistra Hospital,Jakarta, Indonesia; 15University of Santos Tomas, Manila, Philippines; 16IMS & SUM Hospital, Odissa, India

Background and Aims: Autoimmune hepatitis(AIH)is considered less common or is underdiagnosed in the Asian-pacific region. Due to this, flare as a cause of acuteon chronic liver failure(ACLF) is often missed and treatment is delayed. We aimed at defining the clinical, histopathological spectrum and role of steroid therapy in

AIH-ACLF.

Patients and Methods: Patients with AIH-ACLF, prospectively recruited and followed between 2012-2017, were analyzed from the APASL ACLF Research Consortium(AARC) data base, involving 9 Asian countries and 15 centres. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group (IAIHG) score or simplified AIH score-probable or definite with histopathology in 90%; and diagnosis of ACLF was based on APASL definition.

Results: Of 2,825 ACLF patients, 82 (2.9%) fulfilled the criteria of AIH (mean age 42.09 ± 18.12 yr, 70% females). Etiology of AIH flare could be ascribed in 8(9.7%) to drugs and in 6(7.3%) to virus. At baseline, mean bilirubin was 18.6 ± 8.2mg/dl, INR 2.46 ± 0.76, CTP score 11.75 ± 1.39 and MELD score 27.65 ± 6.49. Mean IgG level was 21.61 ± 7.32 g/dl, with nearly 49% patients as seronegative. Of seropositive patients, 43.9% were ANA(1:80), 19.5% ASMA and 3.7% antiLKM-1 positive. Median HAI was 10[IQR: 7-12]; 43.5% had underlying cirrhosis; 56% significant parenchymal  necrosis (bridging and confluent necrosis) and 90% moderate to severe interface activity. Twenty eight (34%) patients received steroid therapy, with their baseline bilirubin and severity score comparable to those not receiving steroids. Patients who received steroid had a significantly shorter duration of ICU stay(median 1.5 Vs.4 day;p<0.001) and improved 90 day survival(75% Vs 48.1%;p=0.02). Six (21.4%) patients developed infection on steroid therapy; though incidence was not different from those not on steroids. Factors significantly associated with steroid response were age (p=0.03), bilirubin (p=0.008), INR (p=0.05), MELD score (p=0.04) and presence of hepatic encephalopathy (p=0.004) at baseline. On multivariate analysis, only MELD score (<27) predicted steroid response (AUROC=0.86; 83.3% sensitivity, 78.9% specificity).

Conclusions: AIH is an uncommon cause of ACLF in Asia Pacific region and therefore, requires a high degree of suspicion, a low threshold for transjugular liver biopsy as nearly half the patients are seronegative. Early stratification (MELD<27) to steroid therapy or liver transplantation ( MELD>27) would reduce ICU stay and help improve outcomes.

 

Hepatic encephalopathy and ammonia can predict 28 day mortality in acute on chronic liver failure in a dynamic manner- Results of multination study from APASAL-ACLF Research Consortium.

Abhinav Verma1, Ashok K. Choudhury1, Barjesh C. Sharma1, Manoj Kumar1, Rakhi Maiwall1, Yogesh K. Chawla2, Sunil Taneja2, Mamun A. Mahtab3, Hasmik Ghazinyan4, Qin Ning5, Ke Ma5, Syed M. Jafri6, Harshad Devarbhavi7, Dr S S8, Sombat Treeprasertsuk9, Guan Huei Lee10, Zhongping Duan11, C.E. Eapen12, Ashish Goel12, Deepak N. Amarapurkar13, Akash Shukla14, Jinhua Hu15, Samir R. Shah16, Laurentius A. Lesmana17, Jose D. Sollano18, Gian Carpio18, Zaigham Abbas19, Padaki Nagaraja Rao20, Abdulkadir Dokmeci21, Mohan Prasad22, Salimur Rahman3, Manoj K. Sahu23, Diana A. Payawal24, George Lau25, Vivek A. Saraswat26, Mohammad Fazal Karim27, Osamu Yokosuka28, Vikram Bhatia1, Ankur Jindal1, Kapil D. Jamwal1, Saggere M. Shasthry1, Guresh Kumar29, Priyanka Jain29, Irene Paulson29, Karan Kumar1, Shiv K. Sarin1;

1Hepatology, Institute of liver and biliary sciences, Delhi, India; 2HEPATOLOGY, PGIMER, CHANDIGARH, India; 3Hepatology, Bagbandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 4Hepatology, Nork Clinical hospital of infectious diseases, Yerevan, Armenia; 5HEPATOLOGY, Tongi Hospital, Beijing, China, BEIJING, China; 6HEPATOLOGY, Aga Khan University, KARACHI, Pakistan; 7gastroenterology, St John’s Medical College, BANGLORE, India; 8HEPATOLOGY, Hospital Selayang, Batu Caves, SELANGOR, Malaysia; 9Medicine, Chulalongkorn University, Bangkok, Thailand; 10Medicine, National University of Health System, Straits Settlements and Federated Malay States, Singapore; 11HEPATOLOGY, Youan Hospital, BEIJING, China; 12Hepatology, CMC vellore, VELLORE, India; 13gastroenterology, Bombay Hospital & Medical Research Center, Mumbai, India; 14gastroenterology, KEM Hospital, Mumbai, India; 15Liver failure treatment & research center, 302 hospital, BEIJING, China; 16gastroenterology, Global hospital, Mumbai, India; 17Medicine, Medistra Hospital, JAKARTA, Indonesia; 18Medicine, University of Santo Tomas, MANILLA, Philippines; 19urology, Ziauddin University Hospital, Karachi, KARACHI, Pakistan; 20gastroenterology, Asian Institute of gasteroenterology, Hyderabad, India; 21Medicine, Ankara University School of Medicine, ANKARA, Turkey; 22gastroenterology, VGM Hospital, Coimbatore, Coimbatore, India; 23IMS &SUM hospital,Odisa, Bhubaneswar, India; 2425 Dr Diana A Payawal dianapayawal@yahoo.com Cardinal Santos Medical Center, Manila, Phillipines, MANILLA, Philippines; 25Humanity and Health Medical Group, Hepatitis Research Foundation, HONG KONG, China; 26gastroenterology, SGPGI, Lucknow, Lucknow, India; 27HEPATOLOGY, drfazalkarim@gmail.com, DHAKA, Bangladesh; 28Chiba University, Tokyo, Tokyo, Japan; 29ILBS, New Delhi, India, DELHI, India

Background: ACLF is a distinct entity with high short term mortality. Presence of advanced hepatic encephalopathy (HE) is poor predictor of survival in ALF. High ammonia levels predict poor non transplant survival in ALF. The predictive ability of ammmonia(NH3) in ACLF is not well studied. We aimed to study the role of level of NH3 and grade of HE in predicting overall survival in patients of ACLF.

Methods: Patients with ACLF, prospectively recruited and followed between 2012 April to April 2017 in the APASL ACLF Research Consortium (AARC) data base were included in the study. Patients with HE at baseline (Gp. A) and those without HE (Gp. B) were analysed. The grade of HE, plasma lactate and arterialNH3 levels were obtained at baseline, Day 4 & 7 and were correlated with 28 day  survival.

 Result: Out 1,281 ACLF pateints, HE was present in 291 (Gp A, 22.7%). Between Gr. A and B, the age (45.1±12.7yr vs. 46.5±14.3 yr, p=0.19), gender (males 86.2% vs.78%, p=0.11) were comparable.

Group A patients were relatively sick with higher MELD (32.5±7.4 vs. 27.6±6.8, p<0.001) and SOFA score (10.6±3.5 vs. 8.6±2.8, p<0.001). The NH3 level [HR=3.721(95CI 2.03-6.79), p<0.001), presence of HE [HR=3.85(95CI1.93-7.65), p<0.001], high lactate [HR=1.85(95CI1.45-2.34), p<0.001], INR [HR=1.24(95CI1.19-1.29), p<0.001], creat. [HR=1.16(95CI1.12-1.20), p<0.001] and total bil [HR=1.024(95 CI 1.016-1.033), p<0.001] were independent predictors of 28 day mortality. NH3 level at baseline was higher in Gr. A than B(175.8±90 vs 110.6±72 µg/dl, p<0.001). Serum NH3 was higher in grade III-IV HE in Gr.A than Gr.B(145.7±72.7µg/dl vs.186±90.2µg/dl, p=0.004). Presence of HE predicted 28day mortality in a dynamic manner(HR=2.1(95CI1.75-2.51), p<0.001) and presence of

grade III-IV HE anytime in first week was associated with high mortality (Gr.A vs.B; 14.3% vs. 4.9%, p<0.001). Baseline ammonia of >140µg/dl predicted 28 day mortality with AUROC of 0.732 (p<0.001), sensitivity of 75% and 73% specificity. Change in ammonia level at D4 and D7 from

baseline predicted 28 days mortality(p<0.001). Non-survivors had ammonia level >140µg/dl at any time point in first 7 days. HE grade III-IV and ammonia >140µg/dl, taken together at any time-point in first week was an excellent dynamic model to predict 7 and 28 day mortality in ACLF(p<0.001). Conclusion: Presence of Grade III-IV HE and ammonia level >140µg/dl either alone or in combination

at any time during first 7 days of ACLF presentation, can serve as a simple and reliable dynamic model to predict 7 and 28 day mortality in patients of ACLF presenting with HE. This could help in early stratification for liver transplant beyond the MELD allocation criteria.

 

Dynamic AARC-AKI score determines Extrarenal Organ Failures and Bacterial Infection in patients with Acute on Chronic Liver Failure

Rakhi Maiwall1, Ashok K. Choudhury1, Barjesh C. Sharma1, Manoj Kumar1, Harshad Devarbhavi2, Mamun A. Mahtab3, Zhongping Duan4, Yu Chen4, Qin Ning5, Ke Ma5, Jidong Jia6, CE Eapen7, Ashish Goel7, Yogesh K. Chawla8, Sunil Taneja8, Soek Siam Tan9, Dong Joon Kim10, Hasmik Ghazinyan11, Jinhua Hu12, Guan Huei Lee13, Sombat Treeprasertsuk14, Laurentius A. Lesmana15, Saeed S.Hamid16, Amna S. Butt16, Syed M. Jafri16, Deepak N. Amarapurkar17, Akash Shukla18, Samir R. Shah19, Zaigham Abbas20, Jose D. Sollano21, Gian Carpio21, Manoj K. Sahu22, George Lau23, Padaki Nagaraja Rao24, Mohammad Fazal Karim30, Diana A. Payawal25, Vivek A. Saraswat26, Mohan Prasad27, Man Fung Yuen28, Salimur Rahman3, Abdulkadir Dokmeci29, Kapil D. Jamwal1, Lovkesh Anand1, Guresh Kumar1, Priyanka Jain1, Ankit Bhardwaj1, Irene Paulson1, Shiv K. Sarin1, APASL ACLF Working Party1; 1Hepatology, ILBS, New Delhi, India; 2Department of Hepatology, St John’s Medical College, Banglore, India; 3Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 4Department of Hepatology, Youan Hospital, Capital Medical University, Beijing, China; 5Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 6Liver Research Center, Beijing Friendship Hospital, Beijing, China; 7Department of Gastroenterology and Hepatology, Christian Medical College, Vellore, India; 8Department of Hepatology, Post Graduate Institute of

Medical Education and Research, Chandigarh, India; 9Department of Gastroenterology and Hepatology, Selayang Hospital, Kepong, Malaysia; 10Internal medicine, Hallym University

College of Medicine, Seoul, Korea (the Republic of); 11hepatology, Nork Clinical Hospital, Yerevan, Armenia; 12liver failure treatment and research, 302 Militiary Hospital, Beijing, China; 13Department of Gastroenterology, National University of Health System, Singapore, Singapore; 14Internal Medicine, Chulalongkorn University, Bangkok, Thailand; 15Digestive Disease & Oncology, Medistra Hospital, Jakarta, Indonesia; 16Medicine, Aga Khan University, Karachi, Pakistan; 17gastroenterology, Bombay Hospital, Mumbai, India; 18Hepatology, KEM hospital, Mumbai, India; 19Hepatology, Global Hospital, Mumbai, India; 20Hepatogastroentrology, Ziauddin University,

Karachi, Pakistan; 21Hepatology, University of Santo Tomas Hospital, Manila, Philippines; 22Gastroenterology and Hepatology, IMS &SUM hospital, Odissa, India; 23Gastroentrology and Hepatology, Humanity and Health Medical Group, Hepatitis Research Foundation, China, China; 24Asian Institute of gasteroenterology, Coimbatore, India; 25Medicine, Cardinal Santos Medical Center, Manila, Philippines; 26Gastroentrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India; 27Gastroentrology, VGM Hospital, Coimbatore, India; 28Medicine, Queen Mary Hospital, Hong Kong, Hong Kong, China; 29Gastroenterology, Ankara University School of Medicine, Ankara, Turkey; 30Hepatology, Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh

Background and Aim: AKI is a dynamic event in patients with Acute-on-chronic liver failure (ACLF) and is associated with poor prognosis. AKI can predispose to infections and in animal models has been shown to cause remote organ dysfunction. The course of AKI in progressive liver failure in a cirrhotic is not well understood. We studied the association between the dynamic course of AKI in

ACLF patients and occurrence of infections, extrarenal organ failures(E-OFs) and 30-day mortality and developed a dynamic score (AARC-AKI Score) using a derivative (Gr.A, n=1060) and validation cohort(Gr.B, n=1579).

Methods: Prospectively collected data from AARC data base was analysed. The AKI-score was constructed by the beta-coefficients of the course (resolution vs. persistent vs progression) and stage of AKI (0:1:2:3) from 12 different combinations of clinical course patterns at each time

point (Day0-3,4-7,8-15) using repeated measures; Generalised Estimating Equations (GEE) for prediction of 30-day mortality.

Results: Of the 2639 patients with ACLF; mean age 45±12 yr, 86% male, 45% alcoholic, 1461 with AKI, of which 63% had AKI at admission [Stage1:2:3(%); 31:58:11] while 37% developed new AKI [58%:32%:10%] respectively. The peak AKI stage in majority was 2 or 3 i.e. 62%; peak stage[1:2:3(%) 38:41:21]. At last follow-up, AKI resolved in 37.3%, remained stable in 46.3% and progressed in 16.4%. The AARC-AKI Score developed from the GEE model showed a progressive increase in mortality (HR, 95%CI) (1.31, 1.29-1.34), E-OFs (1.23, 1,21-1.25) and infections (1.16, 1.14-1.17) at 30-day with increasing risk scores from 1-9 in both groups and showed a good discrimination and calibration (Harrell’s C-0.76). A score of >7 at day 15 was associated with 99% mortality. A significant increase in 30-day mortality (HR,95% CI) (1 vs 3.5, 3.2-3.8 vs 7.4, 6.7-8.1), E-OFs (1 vs 2.2,1.9-2.3 vs 4.1, 3.7-4.6) and development of bacterial infections (1 vs 1.8, 1.6-2 vs 2.7, 2.5-3.1) was noted on stratification of patients into 3 classes derived from AKI score (Class 1-1-3, Class 2-4-6 and Class 3-7-9) in both group A and B respectively.

Conclusions: Almost 50% of patients with ACLF manifest with AKI which, in majority is severe, resolves in a third and follows a stable or progressive course in the rest. The stage and course of AKI impacts function of other organs, predisposes to bacterial infections and is an independent predictor of 30-day mortality. Sequential use of AARC-AKI score for stratifying patients and intervening in the first two weeks may be the therapeutic golden-window for preventing AKI related mortality in ACLF.

 

 

Validation of TPPM Score in predicting shortterm survival in HBV-ACLF patients: a  multinational study from APASL ACLF Research Consortium (AARC)

Tao Chen1, Ke Ma1, Ashok K. Choudhury2, Manoj K. Sharma3,Zhongping Duan4, Shaojie Xin5, Yuemin Nan13, Tao Han6,Soek Siam Tan7, Jinhua Hu8, Saeed S. Hamid9, Amna S. Butt9,Syed M. Jafri9, Guan Huei Lee10, Hasmik Ghazinyan11,Yogesh K. Chawla12, Sunil Taneja12, Akash Shukla14, Man Fung Yuen15, Jidong Jia16, Zaigham Abbas17, Sombat Treeprasertsuk18,Harshad Devarbhavi19, Abdulkadir Dokmeci21,Deepak N. Amarapurkar20, Manoj K. Sahu22, Laurentius A. Lesmana23,George Lau24, Osamu Yokosuka25, Wei Guo1,Shiv K. Sarin2, Qin Ning1; 1Tongji Hospital, Tongji MedicalCollege, Huazhong University of Science and Technology,Wuhan, China; 2Institute of Liver and Biliary Sciences, New Delhi, India; 3Bangabandhu Sheikh Mujib Medical University,Dhaka, Bangladesh; 4Youan Hospital, Capital Medical University,Beijing, China; 5Youan Hospital, Capital Medical University,Beijing, China; 6Third central hospital, Tianjing, China;7Selayang Hospital, Kepong, Malaysia; 8302 Military Hospital,Peking University Health Science Center, Beijing, China; 9Aga Khan University Hospital, Karachi, Pakistan; 10National University of Health System, Singapore, Singapore; 11Nork Clinical

Hospital of Infectious Diseases, Yerevan, Albania; 12Post Graduate Institute of Medical Education and Research, Chandigarh,India; 13Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University,Shijiazhuang, China; 14KEM Hospital, Mumbai, India; 15Queen Mary Hospital, Hongkong, Hong Kong; 16Beijing Friendship Hospita, Beijing, China; 17Ziauddin University, Karachi, Pakistan; 18Chulalongkorn University, Bangkok, Thailand; 19St John Medical College, Banglore, India; 20Bombay Hospital and Medical Research Centre, Mumbai, India; 21Ankara University School of Medicine, Ankara, Turkey; 22IMS &SUM hospital,Odisa, India; 23Digestive Disease & Oncology Centers, Medistra

Hospital, Jakarta, Indonesia; 24Humanity and Health Research Centre, Hongkong, Hong Kong; 25Departments of Gastroenterology and Nephrology, Graduate School of Medicine,Chiba, Japan

Objective: Tongji prognostic predictor model (TPPM)for HBV- ACLF, includes bilirubin (TBIL), INR, number of complications and HBV DNA and has been validated for its predictive value from a single center. We aimed to compare TPPM model with model of end-stage liver disease (MELD) and MELD-Na in predicting short term survival in patients with HBV-ACLF from APASL ACLF Research Consortium (AARC)

data base, from 26 countries.

Patients and Methods: In this prospective-retrospective study, we enrolled 471 (302males) patients with HBV-ACLF who were hospitalized and treated with anti-HBV nucleot(s)ide analogues (NUCs) and

traditional internal medicines. TPPM, MELD and MELD-Na score were measured at hospitalization and 90-day survival was predicted.

Results: Among the 471enrolled patients, 302 (64.1%) survived and 169 (35.9%) were non-survivors at 90-day. The baseline characters including age (44.59±13.62 vs. 45.73±14.86yr), gender (male/female,

208/263 vs. 141/161), ALT (491±830vs. 566±773IU/ml), AST (566±723 vs. 602±864, IU/ml), TBIL (18.2±9.1 vs. 21.7±9.5, mg/dl) and INR (2.07±0.69 vs. 2.65±1.27)did not show significant difference (p > 0.05) between survivors and non-survivors. The baseline prognostic scores of TPPM,MELD and MELD-Na between survivors and non-survivors were 0.87±0.15 vs. 0.79±0.22 (p<0.001), 24.52±5.69

vs. 29.16±6.57 (p=0.013) and 27.27±5.67vs. 31.62±5.37(p=0.043). Using the Hosmer-Lemeshow test, the validation of the TPPM score for HBV-ACLF demonstrated a good degree of fit with prediction of disease prognosis. Based on this large cohort of patients, the TPPM score with an AUC of 0.732 was found superior to the MELD score and MELD-Na score, which had an AUC of 0.712 and 0.714 in predicting 90-day mortality in HBV-ACLF.

Conclusion: The TPPM scoring system has been found to be truly predictive and has been validated in the international AARC database. It shows its superiority in a disease specific scenario of HBV ACLF compared with MELD and MELD-Na, and is recommended for patient stratification at admission for NUCs and/or liver transplantation.

 

EASL 2017

 

Etiology, time frame and spectrum of decompensation in 6236 patients of cirrhosis liver across Asia: a multinational study from APASL ACLF Research Consortium (AARC)

A. Choudhury1, M.K. Sharma1, B.C. Sharma1, R. Maiwal1, V. Pamecha2, R. Moreau3, Y.K. Chawla4, A. Duseja4, M.A. Mahtab5, S. Rahman5, S.S. Hamid6, A.S. Butt6, W. Jafri6, S.S. Tan7, H. Devarbhavi8, D. Amarapurkar9, Q. Ning10, C.E. Eapen11, A. Goel11, D.J. Kim12,

H. Ghazinyan13, G. Shiha14, G.H. Lee15, Z. Abbas16, D.A. Payawal17, A.K. Dokmeci18, M.F. Yuen19, L.A. Leshmana20, A. Sood21, A. Chan22, G.K. Lau23, J.D. Jia24, Z. Duan25, C. Yu25, O. Yokosuka26, P.N. Rao27, S. Shah28, V.G.M. Prasad29, M.K. Sahu30, A. Shukla31, J. Hu32, S. Treeprasertsuk33, V.Arora1, K. Mishra1, P. Bhatia1, P. Jain1, G. Kumar1, S.K. Sarin1 and Apasl ACLF working party1. 1Department of Hepatology and Transplant; 2Department of Hepatobiliary Surgery and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India; 3Centre de recherche sur l’Inflammation(CRI), Paris, France; 4Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India; 5Department Of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 6Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan; 7Department of Gastroenterology and Hepatology, Selayang Hospital, Kepong, Malaysia; 8Department of Gastroenterology and Hepatology, St. John Medical College, Banglore; 9Department of Gastroenterology and Hepatology, Bombay Hospital and Medical Research, Mumbai, India; 10Department of Infectious Disease, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 11Department of Gasterointestinal Sciences, Christian Medical College, Vellore, India; 12Center for Liver and Digestive Disease, Hallym University Chuncheon Sacred Heart Hospital, Gangwon-Do, Korea, South; 13Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, Yerevan, Armenia; 14Department of Internal

Medicine, Egyptian Liver Research Institute and Hospital, Cairo, Egypt; 15Department of Gasteroenterology and Hepatology, National University Health System, Singapore, Singapore; 16Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation,

Karachi, Pakistan; 17Department of Hepatology, Cardinal Santos Medical Center, Manila, Philippines; 18Department of Gastroenetrology, Ankara University School of Medicine, Ankara, Turkey; 19Department of Medicine, The University of Hong Kong, Hong Kong, China; 20Division of Hepatology, University of Indonesia, Jakarta, Indonesia; 21Department of Gastroenterology, Dayanand Medical College, Ludhiana, India; 22Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, The University of Hong Kong, Hong Kong; 23The Institute of Translational Hepatology; 24Liver Research Center, Beijing Friendship Hospital, Capital Meical University; 25Beijing Youan Hospital, Capital Medical University, Beijing, China; 26Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan; 27Asian Institute of Gastroenterology, Hyderabad; 28Department of Hepatology, Global Hospital, Mumbai; 29V G M Hospital, Coimbatore; 30Institute of Medical Sciences and SUM Hospital, Bhubneshwar; 31KEM Hospital and Seth G S Medical College, Mumbai, India; 32Millitary Hospital, Beijing, China; 33Division of Gastroenterology, Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand E-mail: aarc@aclf.in

Background and Aims: Onset of decompensation in cirrhosis is associated with poor outcome. Identifying the cause for decompensation and liver failure early may guide the definitive therapy. Aim was to address the etiology, time frame and spectrum of decompensation in patients with cirrhosis of liver.

Methods: Patients of cirrhosis admitted with decompensation across 40 centres in Asia since October 2012 to October 2016 were prospectively enrolled. The etiology, time frame, spectrum of decompensation and predictors of mortality were analyzed.

Results: Total of 6326 patients [mean age 48.2 ± 11.5 years, 84% male, Mean CTP 10.4 ± 2.2 and MELD Na-30.4 ± 11.9], with a follow up 23 [range 3–4402] days had a mortality of 23.2%, 29.2% and 32.7% at day 28, 90 and 365. Alcohol related CLD constituted 49.4% (n = 3032). Acute insult could be identified in 80% cases; of which extra-hepatic 49%, hepatic 46% and unknown 5% cases respectively. Presence of acute insult increased the one-year mortality [HR 1.82, 95 CI = 1.59– 2.08, p < 0.001]. Sepsis 26.5%, alcoholic hepatitis 23.5%, acute variceal bleed 17.3%, Drugs 8.3%, HBV reactivation 7.8% and acute viral hepatitis 4% were the precipitant. The 1 year mortality was higher with hepatic [HR1.93, 95 CI = 1.67–2.23, p < 0.001] than extra hepatic insult [HR 1.74, 95 CI = 1.49–2.02, p < 0.001]. The decompensation were ascites 14.4% (n = 911), hepatic encephalopathy 4.3%, jaundice 4%, and acute variceal bleed 3.7%; though 2 or more were seen in majority 61.4% (n = 3885). The acute insult leading to decompensation in 1–3 months was associated with worse outcome [HR 1.29, 95 CI = 1.16–1.44, p < 0.001] than those with >3 months [HR 1.17, 95 CI =0.97–1.39, p = 0.08] and < 1 month. Presence of prior decompensation associated with improved survival [HR = 0.71, 95 CI 0.64–0.79, p <0.001]., whereas the current decompensation occurring within or after 1 year of index did not influence the mortality [HR 1.12, 95CI =0.99–1.28, p = 0.08]. Hb and albumin were protective, whereas INR, bilurubin and leukocyte count were independent predictors for 90 and 365 day mortality.

Conclusions: The current multinational AARC database helps to chronologically define and add prognostic relevance to the term decompensation in cirrhosis. Presence of a preciptant, predominant hepatic insult and hepatic mode of decompensation (higher bilirubin, INR and albumin) occuring with in <3 month in absence of a prior decompensation could prognosticate a patient of cirrhosis with onset of decompensation.

APASL 2017

 

A dynamic web based prognostic AARC score calculator predicts the survival better than existing MELD, CLIF-SOFA in patients of ACLF

Ashok Kumar Choudhury1, Manoj Kumar Sharma1, Brajesh Chandra Sharma1, Rakhi Maiwall2, Viniyendra Pamecha1, Yogesh Kumar Chawla3, Mamun Al Mahtab 4, Salimur Rehman5, Saeed S. Hamid6, Amna Subhan Butt6, Soeak S. Tan7, Harshad Devarbhavi8, Deepak N. Amarpurkar9, Qin Ning10, C. E. Eapen11, D. J. Kim12, Chang W. Kim13, Hashmik Ghazinian14, Gamal Shiha15, Guan Huei Lee16, Seng Gee Lim17, Zaigham Abbas18, Ajit Sood19, Albert Chan20, George K. Lau21, Zhongping Duan22, Jidong Jia23, Jin Hua Hu24, L. A. Lesmana25, Osamu Yokosuka26, Diana A. Payawal27, Jose D. Sollano28, Sombat Treeprasertsuk29, A. Kadir Dokmeci30, Anil Kumar Arora31, Guo Hong Han32, Akash Shukla33, Debi Prasad34, Chienhao Huang35, Samir Shah36, Manoj Kumar Sahoo37, Priyanka Jain1, Guresh Kumar1, Shiv Kumar Sarin2, APASL ACLF Research Consortium (AARC) for APASL ACLF Working Party 1Institute of Liver and Biliary Sciences, New Delhi, India; 2Institute of Liver and Biliary Sciences, New Delhi, India; 3PGIMER, Chandigarh, India; 4Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh; 5Associate Professor, Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka, Bangladesh; 6Aga Khan University Hospital, Karachi, Pakisthan; 7Selayang Hospital, Batu Caves, Malaysia; 8St John Medical College, Bengaluru, India; 9Bombay Hospital and Medical Research Center, Mumbai, India; 10Institute of Infectious Disease, Pune, India; 11Christian Medical College, Vellore, Tamil Nadu, India; 12Chuncheon Sacred Heart Hospital, Chuncheon, South Korea; 13The Catholic University of Korea, College of Medicine, Seoul, South Korea; 14Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia; 15Egyptian Liver Research Institute and Hospital (ELRIAH), Dakahlia, Egypt; 16National University Health System, National University of Singapore, Singapore, Singapore; 17Department of Pathology, National University Hospital, National University Health System, Singapore, Singapore; 18Dr. Ziauddin University Hospital, Karachi, Pakistan; 19Christian Medical College, Ludhiana, India; 20The University of Hong Kong, Pokfulam; 21Institute of Translational Hepatology, Beijing 302 Hospital, Beijing; 22Hepatology Institute Capital Medical University Beijing, Beijing; 23Beijing Friendship Hospital, Capital Medial University, Beijing; 24Millitary Hospital Beijing, Beijing; 25Digestive Disease and Oncology Centers, Medistra Hospital, Jakarta, Indonesia; 26Chiba University, Chiba, Japan; 27Fatima Medical University Hospital, Valenzuela Metro Manila, Valenzuela, Philippines; 28Cardinal Santos Medical Center, Metro Manila, Philippines; 29Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 30Ankara University School of Medicine, Ankara, Turkey; 31Sir Ganga Ram Institute of Post Graduate Medical Education and Research, New Delhi, India; 32Xijing Hospital of Digestive Disease, Xi’an; 33KEM Hospital and Seth GSMC, Mumbai, India; 34University of Aukland, Auckland, New Zealand; 35Division of Hepatology, Department Of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Taoyuan City, Taiwan, Linkou Medical Center, Taipei City; 36Global Hospital, Mumbai, India; 37Department of Gastroenterology, IMS and SUM Hospital, Bhubaneswar, India

Background: Acute on chronic liver failure (ACLF) is associated with the rapid worsening of liver failure with high mortality. Prediction of survival and early intervention can improve the outcome. Aim was to derive a dynamic, web based prognostic model and web based calculator for predicting the outcome in patients of ACLF.

Methods: Total 1402 ACLF cases with 90 days follow up enrolled into the APASL ACLF Research Consortium (AARC) were analyzed. A derivation set of 480 cases analyzed for a prognostic model and calibrated in 922 cases validation set. A equation based dynamic model was derived to predict the survival and was developed to a web based calculator.

Result: Of all the baseline parameters, total bilirubin, Creatinine, Lactate, INR and hepatic encephalopathy were found to be the independent predictors for 28 days mortality. AARC ACLF score was developed by an equation i.e. Score = 10*(2.32*loge lactate(meq/l) + 0.55* loge creatinine(mg/dl) + 0.79* loge Bilirubin (mg/dl) + 0.05* loge INR + (1.24 if HE = Grade III/IV, or 0.88 if Grade I/II = 2 or 1 if no HE) - 5.13. The concordance of all patient pairs in the derivation and validation set showed a good fit (Harrell’c 0.77 and Sommers’ D 0.53 respectively) for the equation based score. The expected frequency and observed frequencies from derivation set (R2 = 0.97) showed a good matching into the validation set (R2 = 0.94). The prognostic model has a good predictibility as in AUROC of 0.80 (derivation cohort) and 0.76 (validation cohort). The score was better than the MELD and CLIF SOFA with an AUROC of 0.81 with a sensitivity and specificity of 75 and 81% negative predictive value for 28 and 90 days survival. The score had a minimum of 16 and maximum of 113(Can be gropued to score of 40–80). The 28 days cumulative mortality showed an exponential rise i.e. from 15% (score\40) to 50% (score 54) to 80% (score 65) and more than 95% mortality beyond 83 at admission (p = 0.001). A score below 41 at baseline and within first week was observed in survivors and that

for nonsurvivor being[56 at anytime ponit (p = 0.001). A web based calculator could predict the 28 and 90 days mortality with 75%

accuracy at anytime points and is dynamic one.

Conclusion: The AARC ACLF score is dynamic and inclusion of hepatic encephalopathy and lactate enabled the assessment with the easily measurable bedside parameters and is better than the existing models.

 

Hepatitis E and acute on chronic liver failure: outcome and predictors of mortality in Asia pacific region

Amna Subhan Butt1, Saeed Hamid1, APASL-ACLF Research Consortium

1Aga Khan University Hospital, Karachi, Pakistan

Background: One of the distinctive factors that could lead to acute on chronic liver failure is acute hepatitis E (HEV). However, most of available data carries the limitation of smaller sample size or center based experiences. Herne, the current study aims to analyze the APASL-ACLF research consortium (AARC) database to evaluate the clinical and biochemical profile and predicting factors of 90 days mortality in patients with ACLF triggered by acute hepatitis E infection. Moreover, various existing prognostic models for ACLF were compared.

Methods: APASL-ACLF research consortium (AARC), consisting of 24 tertiary centers across Asia–Pacific regions, maintains an online database for patients diagnosed to have ACLF according to APASL criteria. All patients who had ACLF with acute hepatitis E were reviewed for the current study.

Result: A total of 2059 patients were enrolled and most of information was available for 1402. Out of 1402 patients, 188(14.3%) had acute deterioration due to HEV. Mean age was 48.77 ± 13.71 years and 85.1% were male. The most common cause of chronic liver disease was alcohol (26.4%), cryptogenic cirrhosis (26.4%) and hepatitis B infection (23.6%). Overall 67.5% patients survived and only one patient underwent for liver transplantation. On univariate analysis Presence of PSE, sepsis, AKI on presentation, platelet counts, serum ureae, total bilirubin, INR, ALT, AST, MELD, SOFA score were the factors associated with mortality. However on multivariate analysis presence of PSE (OR 2.01, 95% CI 1.16–3.47, p 0.01), sepsis (OR 1.42, 95% CI 0.79–2.55, p 0.04), total bilirubin at base line (OR 1.04, 95% CI 1.01–1.07, p 0.001) were the factors associated with mortality. When we compared various prognostic models MELD and CLIF-SOFA were found to have higher accuracy.

Conclusion: Acute hepatitis E is one of the leading causes of ACLF in Asia pacific region and associated with high mortality without liver transplantation. Presence of PSE, AKI, sepsis and total bilirubin at base line were the factors associated with mortality.

EASL 2018

 

Therapeutic plasma-exchange improves systemic inflammation and survival in patients with acute on chronic liver failure

R. Maiwall1, A. Choudhury1, Z. Duan2, Y. Chen2, J. Hu3, H.L. Ghazinyan4, Q. Ning5, K.Ma5, G.H. Lee6, S.G. Lim6, S. Shah7, C. Kalal7, A.K. Dokmeci8, G. Kumar1, P. Jain1, I. Paulson1, S.K. Sarin1, A. Choudhury9. 1ILBS, Hepatology, Delhi, India; 2Beijing You’an Hospital, Hepatology, Beijing, China; 3302 Millitary Hospital, Beijing, China; 4Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia; 5Tongji Hospital, Tongji Medical College; 6Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 7Global Hospital, Mumbai, India; 8Ankara University School of Medicine; 9ACLF APASL Research consortium, AARC Working party

Background and Aims: Systemic Inflammation (SIRS) and infection form the pathogenetic hallmark of organ dyfunction in patients with Acute on Chronic Liver Failure (ACLF). Plasma-exchange (PE) has been shown to improve survival in patients with acute liver failure by combating SIRS, but there is paucity of data in patients with ACLF.We evaluated the role of artificial liver support systems (ALS), plasmaexchange (PE) and liver dialysis (FPSA) as compared to standard medical treatment(SMT) in improving SIRS, development of multiorgan failure(MOF) and survival (SMT) in a large multicentricmultinational cohort of ACLF patients.We also compared the efficacy

of PE as compared to FPSA.

Method: Prospectively collected data from AARC data base was analysed. Matching by propensity risk score (PRS) was done to avoid

selection bias. Competing risk Cox regression analysis was done to identify event specific death.

Results: ACLF patients (n = 1866,aged 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either ALS (n = 162);[PE (n = 131), FPSA (n = 31)] or continued with SMT(n = 1704). Patients treated with ALS had a significantly lower MELD (p = 0.03) and CTP scores (p = 0.04) which was no more evident in the PRS-matched cohort (p > 0.05) (n = 208, [ALS-119;PE-94,LD-25)], SMT-89). Bacterial infections were noted in363(19%), SIRS in 728(39%), which resolved in 511 (27%). ALS was associated with significantly(p < 0.05) higher resolution of SIRS [OR (1.56,1.03–2.34) (1.5,1.03–2.34)], lower persistence [OR(4.6,1.2–18.4) (1.09, 1.01–1.2)], development of new-onset SIRS [OR(4.38,1.1–17.5) (1.2,1.04–1.29)] and MOF [(HR(6.5,4.8–8.7)(7.1,4.5–11.1)] in prematch and PRS-matched cohorts respectively. At 1-month, 656 (35%) died of which 233(35.5%) died of MOF, remaining due to sepsis and other causes. On multivariate Competing risk Coxregression analysis, in both the pre-match and PRS-matched cohorts, treatment with ALS [(HR 0.11, 0.04–0.27), (HR-0.02, 0.002–

0.15) and MELD score [(HR 1.1, 1.08–1.2), (HR 1.09,1.04–1.15) respectively were significant predictors of liver failure related

death. Further, on subgroup analysis PE was associated with a significant survival benefit as compared to FPSA in pre-match (HR 3.4,

1.4–8.1) and PRS-matched (HR 3.9, 1.3–12.3) cohorts.

Conclusion: ALS in patients with ACLF improves systemic inflammation, lowers development of MOF and results in improved survival.

Plasma-exchange has a significant survival benefit over FPSA and should be the therapy of choice in these patients.

Invasive fungal infections in Acute on chronic liver failure An Asia Pacific experience from the AARC consortium

S. Taneja1, S. Rathi2, R.K. Dhiman1, A. Duseja1, A. Choudhury3, P. Jain4 I. Paulson4, H. Deverbhavi5, S.-S. Tan6, C. Eapen7, A. Goel7, S. Shah8, C. Kalal8, A. Kadir Dokmeci9, A. Shukla10, D.J. Kim11, J.-D. Jia12, D. Amarapurkar13, G.H. Lee14, S.G. Lim14, N.R. Padaki15, S.S. Hamid16, W. Jafri17, Z. Abbas18, S.K. Sarin3. 1Postgraduate Institute of Medical Education and Researchch, Hepatology, Chandigarh, India; 2Postgraduate Institute of Medical Education & Research, Hepatology;

3ILBS, NewDelhi, Hepatology; 4ILBS, Hepatology, India; 5St Johns Medical College, Banglore, India; 6Hospital Selayang, Bata Caves, Hepatology, Selangor; 7CMC Vellore, Hepatology; 8Global Hospital, Hepatology, Mumbai, India; 9Ankara University School of Medicine, Hepatology, Turkey; 10KEM Hospital, Hepatology, India; 11Hallym University College of Medicine, Hepatology, Rep. of South Korea; 12Beijing Friendship Hospital, Capital University, Hepatology; 13Bombay Hospital, Hepatology; 14Yong Loo Lin School of Medicine, Hepatology; 15Asian Institute of Gastroenterology, Hepatology, India; 16Aga Khan University, Hepatology; 17Aga Khan University Hospital., Hepatology; 18Ziauddin University Hospital, Karachi

Background & Aims: Invasive fungal infections (IFI) have been associated with higher morbidity and mortality in critically ill cirrhosis patients. Emerging evidence suggests similar trends in patients with acute on chronic liver failure (ACLF).

Aims: To compare the clinical and laboratory profiles of ACLF patients with bacterial and fungal infections and their impact on outcome.

Methods: All patients with proven IFI (culture positive) as per EORTC/MSG guidelines from the APASL-ACLF research consortium prospectively collected database were analysed. Age, gender, and etiologymatched patients of ACLF with bacterial infections were taken as controls. Baseline clinical and laboratory variables, prognostic scores

and length of hospital stay were compared in both groups.

Results: A total of 74 patients with ACLF had evidence of IFI. 101 matched ACLF controls with bacterial infections were randomly selected from the database with bacterial infections. There were no differences in the demographic parameters, acute precipitating events and etiology of chronic liver disease between the groups. The baseline Child-Pugh (Mean } SD- 12.2 } 1.7 vs 12.1 } 1.4; p = 0.75), MELD (32.1 } 7.9 vs 30.4 } 7.8; p = 0.16), APACHE II (20.0 } 6.2 vs 17.9 } 6.4; p = 0.18) and CLIF-SOFA (12.3 } 3.1 vs 12.5 } 2.9; p = 0.7) scores

were similar in both groups. Duration of hospital stay (16.7 } 14.3 vs 13.9 } 10; p = 0.2) and ICU stay (7.1 } 7.8 vs 5.8 } 5.3; p = 0.33) were similar for both groups. The 30- day mortality toowas similar in both groups (OR 1.3, 95% CI 0.7–2.4; p = 0.43), however, in the 90-day mortality; therewas a trend towards higher mortality in the bacterial infection group (OR 1.9, 95%CI 1.0–3.8, p = 0.07). Among the patients with IFI, urinary tract involvement was the most common (n = 54, 73%), followed by pulmonary (n = 15, 20%) and fungemia (n = 8, 11%). There was no difference in the duration of hospital stay or ICU stay between patients with different foci of fungal infection.

Conclusion: Patients with Acute on Chronic Liver Failure with IFIs have similar poor outcomes as those with bacterial infections. The diagnosis and treatment of IFI at baseline in most patients in this study may be responsible for the attenuation of the outcome difference between bacterial and fungal infections. Thus, a high index of suspicion and early diagnosis and treatment may improve the outcome in this group.

 

Impact of organ failure in patients with acute on chronic liver failure (ACLF) and the newly defined AARC liver failure score in predicting 90 days survival-results from APASAL-ACLF research consortium (AARC)

A. Pande1, A. Choudhury1, M. Kumar1, S. Rahman2, H. Deverbhavi3,Z. Duan4, D.J. Kim5, C. Eapen6, Q. Ning7, Y. Chawla8, W. Jafri9, S.-S. Tan10, H.L. Ghazinyan11, D. Amarapurkar12, S. Treeprasertsuk13,G.H. Lee14, J.H. Hu15, L.A. Lesmana16, A. Shukla17, S. Shah18, C. Kalal18, M. Sahoo19, Z. Abbas20, S. Joyes21, F. Karim22, G. Lau23, N.R. Padaki24,D. Payawal25, A. Kadir Dokmeci26, V. Saraswat27, M.-F. Yuen28, V. Gm29,O. Yokosuka30, A. Shrestha31, I. Paulson32, P. Jain32, G. Kumar32,S.K. Sarin1. 1Institute of liver and Biliary Sciences, Hepatology, NewDelhi, India; 2Bangabandhu Sheikh Mujib Medical university, Dhaka, Bangladesh, Dhaka; 3St John Medical College, Bangalore, India; 4Beijing You’an Hospital/Translational Hepatology Institute Capital Medical University, China; 5Hallym University College of Medicine, South Korea/ Beijing Friendship Hospital, Capital University, Beijing, China; 6CMC; 7Tongji Medical College; 8PGI; 9Aga Khan University Hospital; 10Hospital Selayang, Bata Caves, Selangor; 11Nork Clinical Hospital of Infectious Disease Armenia; 12Mumbai; 13Chulalongkorn University, Bangkok;14Yong Loo Lin School of Medicine, National University of Singapore; 15302 Millitary Hospital Beijing, China; 16Medistra Hospital, Jakarta, Indonesia; 17KEM Hospital and Seth GSMC; 18Global Hospital, Mumbai, India; 19IMS &SUM hospital, Odisa; 20Ziauddin University Hospital, Karachi; 21University of Santo Tomas, Manila, Philippines; 22Sir Salimullah Medical College, Mitford Hospital Bangladesh; 23Humanity and Health Medical Group, China; 24Asian Institute of Gastroenterology Hyderabad, India; 25Cardinal Santos Medical Center10 Wilson St. GreenhillsWest San Juan City, Metro Manila; 26Ankara University School of Medicine; 27Sanjay Gandhi Postgraduate Institute, Gastroenterology, Lucknow, India; 28Queen Mary Hospital Hong Kong, China; 29VGM Hospital; 30Chiba University Japan; 31Foundation Nepal Sitapaila Height, Kathmandu; 32ILBS

Background and Aims: Acute hepatic insult leading to liver failure with or without extra-hepatic organ failure leads to a high short-term mortality. However, the impact of organ failure(s) on long- term, i.e. beyond 90 days survival is unknown. We studied the impact of organ failures and on survival beyond 90 days in ACLF patients.

Method: The patients diagnosed to have ACLF (APASL definition) were recruited from 52 centres across Asia Pacific. The data was prospectively collected in this observational study cohort on a predefined format in the database from October 2012 to September 2017. Clinical and laboratory parameters, severity score, organ failures were analysed at baseline and their dynamic changes at D4 and D7 to predict the survival beyond 90 days. Liver failure (serum bilirubin 12.0 mg/dl or more), Kidney failure (2.0 mg/dl or more, oron renal replacement therapy), Cerebral failure (Grade III or IV hepatic encephalopathy), Coagulation failure (INR >2.5 and/or platelet <20.000/cc).

Results: A total of 3037 prospectively enrolled patients, 2553 (84%) males and 484 (15.4%) females with a mean age of 45 } 12.7 years were analyzed. Baseline characteristics in all the groups were comparable. The most common acute insult was alcohol (43%) reflecting a change akin to the West, and followed by viral etiologies (23.3%). The mean baseline MELD score was 28 } 7.6; SOFA score was 8.9 } 3.2; CLIF-SOFA-11.47 } 2.74 and AARC score was 9.89 } 2.15. Therewere 395 (15.8%), 984(39.5%) and 1115 (44.7%) patients with no; one and two organ failures respectively. Mortality at the end of 1 year and 5 year was 955/1855 (51.5%) and 982/1855 (52.5%) respectively. Presence of organ failure increased short-term mortality [HR = 1.99(95CI 1.53–2.26); HR = 4.41(95 CI 3.38–5.75) and 10.33(95 CI 7.64– 13.18)] for 1.2 and >2 organ failures respectively. AARC Score was better than other scores in predicting the 90 day survival outcome.

Conclusion: The organ failure has an impact in predicting the shortterm outcome i.e. 3 months in patients of ACLF. Recently defined AARC Score i.e. a liver failure better predict the outcome than the existing disease severity score.

 

 

Tenofovir is more potent over entecavir in reducing the viral load in patients of hepatitis B reactivation presenting as Acute on Chronic Liver Failure (ACLF)-Results of multination study from APASL-ACLF Research Consortium (AARC)

J. Ahmad*,1, A. Choudhury1, M. Kumar1, M. Al-Mahtab2, S. Rahman2,Q. Ning3, K. Ma3, Z. Duan4, Y. Chen4, J.H. Hu5, J. Hu4, S.-S. Tan6, S.S. Hamid7, A. Subhan7, W. Jafri7, L.A. Lesmana8, R. Lesmana8, H.L. Ghazinyan9, J.-D. Jia10, G.H. Lee11, S.G. Lim11, S. Taneja12, Y. Chawla12, G. Lau13, M. Sahoo14, A. Shukla15, H. Deverbhavi16,M.-F. Yuen17, Z. Abbas18, D. Amarapurkar19, F. Karim20,S. Treeprasertsuk21, A.K. Dokmeci22, A. Goel23, C. Eapen23,D. Payawal24, S. Shah25, C. Kalal25, A. Kulkarni26, S. Chaudhury26, I. Paulson26, P. Jain26, G. Kumar26, S.K. Sarin27. 1ILBS, Hepatology, New Delhi, India; 2Bangabandhu Sheikh Mujib Medical university, Dhaka, Bangladesh; 3Tongji Hospital, Tongji Medical College; 4Beijing You′an Hospital/Translational Hepatology Institute Capital Medical University; 5302 Millitary Hospital Beijing, China; 6Hospital Selayang, Bata Caves, Selangor; 7Aga Khan University Hospital, Karachi; 8Medistra Hospital, Jakarta, Indonesia; 9Nork Clinical Hospital of Infectious Disease Armenia; 10Hallym University College of Medicine, South Korea/Beijing Friendship Hospital, Capital University, Beijing, China; 11Yong Loo Lin School of Medicine, National University of Singapore; 12PGIMER, Chandigarh, India; 13Humanity and Health Medical Group, China; 14IMS &SUM Hospital, Odisa; 15KEM Hospital and Seth GSMC; 16St John Medical College, Bangalore, India; 17Queen Mary Hospital Hong Kong, China; 18Ziauddin University Hospital, Karachi; 19Bombay Hospital & Medical Research Center, Mumbai, India; 20Sir Salimullah Medical College, Mitford Hospital Bangladesh; 21Chulalongkorn University, Bangkok; 22Ankara University School of Medicine; 23CMC, Vellore, India; 24Cardinal Santos Medical Center 10Wilson St. GreenhillsWest San JuanCity, Metro Manila, Philippines; 25Global Hospital, Mumbai, India; 26ILBS; 27ILBS, Hepatology

Background and Aims: Reactivation of hepatitis B is a wellcharacterized syndrome marked by abrupt reappearance or rise of HBV DNA in the serum of a patient with previously inactive or resolved HBV infection. A significant number of patients of spontaneous acute exacerbation of CHB may present with, high HBV DNA, jaundice, liver failure (bilirubin >5 mg/dl), INR >1.5). The presentation, response to therapy and outcome were analyzed.

Method: The patients diagnosed to have ACLF (APASL definition) were recruited from 52 centres across Asia Pacific. The data was prospectively collected in this observational study cohort on a predefined format in the database from October 2012 to September 2017. A total of 560 patients of ACLF (ACLF-HBVr), predominantly

male (361, 64.5%) with mean age 40.6 } 10.4 yr those receiving Nucs i.e. tenofovir(Group-A) orenetcavir(Group-B) or combination (Group-C) were analyzed in relation to viral load at presentation, at 90 days

and its impact on 90 days survival.

Results: 312 patients received Tenofovir (Gr. A) and 203 patients received entecavir (Gr. B) and 35 patients received combination oftenofovir and entecavir (Gr.C). Baseline characteristics in all the groups were comparable. All had high MELD (Gr. A-23.4 } 3.1; Gr.B-25.2 } 2.3; Gr. C-24.1 } 3.1; p = 0.51),CTP score (Gr.A-11.5 } 2.3;Gr.B-11.2 } 1.9 Gr.C-12.4 } 1.9;p = 0.32) and AARC score (Gr.A-11.6 } 2.5,Gr. B-11.9 } 2.1,Gr.C-12.3 } 2.1) were comparable. Cirrhosis was seen on biopsy in 73% (408/560) of patients. HBsAg inclusion bodies were seen in 67%(375/560). Feverwas seen in 91%(509/560) and features of serum sickness in 57/560 (9.8%). Most common cause of reactivation was spontaneous in 88.6% (496 /560) followed by chemotherapy in

7.67% (43/560), HCV therapy (21/560). Baseline DNA-Gr.A-1.2 × 105 }0.8 × 103 IU/ml,Gr.B-2.3 × 105 } 1.1 × 103 IU/ml, Gr.C 4.3 × 107 } 2.1 ×103 IU/ml(p = NS),quantitative HBsAg{Gr.A-5.6 × 103,Gr.B-7.8 × 103,Gr.C-8.1 × 103 (p = NS)}. Tenofovir lead to significant decline in HBV DNA at 3 months i.e., log 3.1 } 0.8 decline in Gr. A compared to log 1.7 } 0.9 in Gr. B and 3.2 } 1.02 log in Gr.C.(p = 0.03). There was comparable decline in HBsAg levels in all the groups {Gr.A-log 1.1 } 0.4; Gr.B log 1.1 } 0.7; Gr. C – 1.5 } 0.9(p = 0.2). Mortality at 3 months was comparable among all groups {Gr.A-36.7%; Gr.B-41.5% and Gr.C-38.3%p = NS}. Baseline DNA, HBsAg (q), bilirubin and INR, cirrhosis on biopsy were significant predictors of mortality on univariate analysis whereas bilirubin and INR were predicators of mortality in multivariate as well. Mean MELD/CTP/SOFA/AARC score were predictors of outcome.

Conclusion: Tenofovir is more potent than entecavir in Asian patients with ACLF-HBVr in reducing viral load, though there is no mortality benefit.

 

 

Hemophagocytic Lymphohistiocytosis (HLH) in patients of acute on chronic liver failure-Results of multination study from APASL-ACLF research consortium (AARC)

H.V. Tevethia1, A. Choudhury2, H.L. Ghazinyan3, C. Eapen4, A. Goel4,Z. Duan5, Y. Chen5, D.J. Kim6, J.-D. Jia6, D. Amarapurkar7, S.S. Hamid8, W. Jafri8, S.-S. Tan9, Z. Abbas10, G.H. Lee11, S.G. Lim11, J.H. Hu12,Y. Chawla13, S. Taneja13, S. Shah14, C. Kalal14, H. Deverbhavi15, O. Yokosuka16, P. Jain17, I. Paulson17, G. Kumar17, S.K. Sarin2. 1ILBS, Hepatology, New Delhi, India; 2ILBS, Hepatology; 3Nork Clinical Hospital of Infectious Disease Armenia, Hepatology; 4CMC, Hepatology, Vellore, India; 5Beijing You’an Hospital/Translational Hepatology Institute  Capital Medical University; 6Hallym University College of Medicine, South Korea/Beijing Friendship Hospital, Capital University, Beijing, China; 7Bombay Hospital & Medical Research Center, Mumbai, India; 8Aga Khan University Hospital, Karachi; 9Hospital Selayang, Bata Caves, Selangor; 10Ziauddin University Hospital, Karachi; 11Yong Loo Lin School of Medicine, National University of Singapore; 12302 Millitary Hospital Beijing, China; 13PGIMER, Chandigarh, India; 14Global Hospital, Mumbai, India; 15St John Medical College, Bangalore, India; 16Chiba University; 17ILBS

Background and Aims: Activation of macrophages in response to acute hepatic insult in patients with pre-existing chronic liver disease presenting as ACLF is a new entity, HLH. Considered to be result of a cytokine storm, uncontrolled inflammatory response, HLH has a poor survival. We studied patients of ACLF to investigate the spectrum, presentation and influence of HLH syndrome on organ failure, disease severity and short-term survival.

Method: The patients diagnosed to have ACLF (APASL definition) were recruited from 52 centres across Asia Pacific. The data was prospectively collected in this observational study cohort on apredefined format in the database from October 2012 to September 2017. A total of 615 patients of ACLF with ferritin >500 μg/l, were analyzed among those fulfilling the HLH criteria [5 of 8 criteria i.e. fever, splenomegaly, bicytopenia,hypofibrinogenemia & ferritin >500 μg/l, irrespective of the bone marrow examination).

Results: Out of 615 patients with ferritin above >500 μg/l, the HLH was seen in 90 (14.6%) cases i.e. full-filling 5 criteria. Males were 84.1% and with mean age of 43.31 } 11.69 yrs. Alcohol was the most common acute and chronic etiology followed by Hepatitis B reactivation. The most common presentation was Jaundice (98.5%), hypofibrinogenemia (93.3%), Spleenomegaly (73.1%) and Fever (61%). Organ failures more than 2, Creatinine >1.49 mg/dl, albumin <2.3 gm/l, INR >2.4, Total Bilirubin >22.3 mg/dl and HE at baseline independently predicted 90 day mortality. Presence of HLH increased mortality (p < 0.001) even though various disease severity scores MELD Na [31.49 } 7.56 vs 28.05 } 7.38,* p = 0.27], SOFA [10.69 } 3.20 vs 8.78 } 3.09, p = 0.84], AARC Score [10.37 } 2.15 vs 9.85 } 2.19, p = 0.79] were not different between those dying versus surviving.

Conclusion: Presence of HLH even in absence of bone marrow confirmation is a poor predictor of outcome in patients of ACLF. Diagnosis of HLH predicts worse prognosis. Newer definition and criteria for HLH and its inclusion in liver severity scores is required in ACLF patients.

 

APASL 2018

 

Usefulness of lactate-free Asian Pacific Association for the Study of Liver acute-on-chronic liver failure (ACLF) Research Consortium (AARC) ‘‘ACLF score for predicting short-term mortality in patients with alcoholic liver disease

Dong Joon Kim1, Tae Yeob Kim12, Ashok Kumar Choudhury11, Ji Dong Jia5, Shiv K Sarin11, Priyanka Jain11, Irene Paulson11, Mamum Al Mahtab4, Salimur Rahman4, Harshad Devarbhavi14, Zhongping Duan6, Chen Yu6, CE Eapen9, Ashish Goel9, Q Ning15, George K Lau10, P N Rao3, Diana Alcantara Payawal7, A. Kadir Dokmeci2, Man Fung Yuen13, V G Mohan Prasad16, Osamu Yokosuka8   1Hallym University College of Medicine, Korea, Republic of; 10Humanity and Health Medical Group, China; 11Institute of Liver and Biliary sciences, India; 12Leeheart Clinic, Korea, Republic of; 13Queen Mary Hospital, China; 14St John Medical College, India; 15Tongji Hospital, Tongji Medical College, China; 16VGM Hospital, India; 2Ankara University School of Medicine, Turkey; 3Asian Institute of Gastroenterology, India; 4Bangabandhu Sheikh Mujib Medical Univerity, Bangladesh; 5Beijing Friendship Hospital, Capital University, China; 6Beijing Youan Hospital, Capital Medical University, China; 7Cardinal Santos Medical Center, Philippines; 8Chiba University, Japa; 9CMC, India

Background: Asian Pacific Association for the Study of Liver (APASL) acute-on-chronic liver failure (ACLF) Research Consortium (AARC) proposed new prognostic scoring system of ACLF including hepatic encephalopathy, bilirubin, international normalized ratio (INR), creatinine, and lactate. However, lactate is not routinely checked in clinical practice of patient with ACLF in some countries. Therefore, we aimed to investigate the predictive accuracy of lactatefree AARC-ACLF score for predicting short-term mortality in patients with alcoholic liver disease (ALD).

Method: A total of 749 ALD patients who had liver failure (bilirubin = 5 mg/dL and INR =1.5) in AARC database were investigated. Diagnostic performances for short-term mortality were compared according to the area under receiver operating characteristic (AUROC) curve. Predictive accuracy of AARC-ACLF score and lactate-free AARC-ACLF score were compared with Child-Turcott- Pugh (CTP) score, model for end-stage liver disease (MELD), and MELD-Sodium (Na), chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores. The findings were validated in Korean ACLF cohort (212 ALD patients with liver failure and 108 ALD patients with ACLF according to AARC definition).

Result: Of 708 patients, 286 (40.4%) and 363 (51.3%) patients died within 30 days and 90 days, respectively. The area under receiver operating characteristics curve (AUC) of AARC-ACLF, DF, ABIC, GAHS, CTP, MELD, and MELD-Na was 0.752 (0.705–0.799), 0.630 (0.575-0.685), 0.658 (0.604-0.711), 0.577 (0.523-0.631), 0.641 (0.589-0.694), 0.705 (0.653-0.756), 0.703 (0.651-0.755), respectively, for 30-day mortality. The AUC of various prognostic scores for the prediction of 90-day mortality is similar. The performance of AARCACLF was superior to that of DF, ABIC, GAHS, CTP, while comparable to that of MELD and MELD-Na in predicting short-term mortality. According to AARC-ACLF grades, short-term cumulative survivals was statistically different (30-day, 82.4, 70.4, and 35.3%, p \0.001; 90-day, 76.9, 56.0, and 26.4%, p\0.001).

Conclusion: Compared to the previous AH prognostic scores, AARC-ACLF score and grades are simple and useful for predicting the short-term mortality in patients with AH. Further studies are needed to confirm these implications.

PROFILE OF ACLF CASES IN ASIA: A MULTICENTRE STUDY

Girish Kumar Pati1, Mamun Al Mahtab6, Salimur Rehman6, Harshad Devarbhavi27, Zhongping Duan8, Chen Yu8, Dong Joon Kim16, Ji Dong Jia7, C E Eapen13, Ashish Goel13, Qin Ning28, Yogesh Kumar Chawla24, R K Dhiman24, Ajay Duseja24, Sunil Taneja24, Saeed Sadiq Hamid3, Amna Subhan Butt3, Wasim Jafri3, Soek Siam Tan17, Hasmik Ghazinian23, Deepak N Amarapurkar9, Sombat Treeprasertsuk12, Guan Huei Lee31, Seng GEE Lim31, Jin Hua Hu2, Laurentius A. Lesmana22, Cosmas Rinaldi Lesmana22, Akash Shukla21, Samir Shah15, Chetan Kalal15, Zaigham Abbas32, Jose D Sollano29, Gian Carpio29, Mohammed Fazal Karim26, George K Lau18, P N Rao5, Diana Alcantra Payawal10, A.Kadir Dokmeci4, Manfung Yuen25, V G Mohan Prasad30, Osamu Yokosuka11, Ananta Prasad14, Priyanka Jain19, Irene Paulson19, Shiv Kumar Sarin19, Manoj Kumar Sahu20, Ayaskant Singh20, Ashok R Choudhury19

Background and Aim: Acute on Chronic Liver Failure (ACLF) is an emerging entity. There is scarce data on profile of ACLF cases in the literature. The present study was undertaken to study the profile of ACLF cases in Asia.

Materials and Methods: ACLF concept was defined as per Asian Pacific Association for the Study of Liver (APASL) consensus criteria 2014. Consecutive cases attending different centers in India and other Asian countries satisfying the above criteria were included and prospectively evaluated for three months.

Results: Out of total 2000 patients with ACLF (mean age: 45.61 ± 12.87 years), male outnumbered the female (Male: Female-5:1). Most common underlying chronic liver disease (CLD) and acute insult were alcoholic liver disease (46.8%) and drinking of alcohol (43.6%) respectively. Ascites and hepatic encephalopathy were present in 74.2% and 35.55% cases respectively. Mean serum bilirubin was 18.85±10.08 mg/dl. 44.25% patients died within 3 months (early mortality). Early mortality was most common in alcoholics (49.15%). The prognostic scorings at base line were CLIF SOFA: 11.7±2.91; APASL ACLF Research Consortium (AARC) SCORE: 9.75±2.11; APACHAE: 15.63±6.68; SOFA: 8.71±3.11; CTP: 11.7±1.59; MELD: 27.92±7.49; MELD Na: 30.95±7.15. All these prognostic scorings were significantly higher in died patients compared to survived patients (p:0.0001). Multivariate logistic regression analysis showed that AARC scoring is the single most important predictor for early mortality.

Conclusion: ACLF patients in Asian countries had high early mortality with majority of death occurring in alcoholics. AARC scoring is the single most important prognostic determinant in prediction of early mortality in ACLF cases.

 

The Prognostic Determinant in Acute on Chronic Liver Failure: A Multicentre Prospective Cohort Study

Girish Kumar Pati1, Mamun Al Mahtab6, Salimur Rehman6, Harshad Devarbhavi27, Zhongping Duan8, Chen Yu8, Dong Joon Kim16, Ji Dong Jia7, C E Eapen13, Ashish Goel13, Qin Ning28, Yogesh Kumar Chawla24, R K Dhiman24, Ajay Duseja24, Sunil Taneja24, Saeed Sadiq Hamid3, Amna Subhan Butt3, Wasim Jafri3, Soek Siam Tan17, Hasmik Ghazinian23, Deepak N Amarapurkar9, Sombat Treeprasertsuk12, Guan Huei Lee31, Seng GEE Lim31, Jin Hua Hu2, Laurentius A. Lesmana22, Cosmas Rinaldi Lesmana22, Akash Shukla21, Samir Shah15, Chetan Kalal15, Zaigham Abbas32, Jose D Sollano29, Gian Carpio29, Mohammed Fazal Karim26, George K Lau18, P N Rao5, Diana Alcantra Payawal10, A.Kadir Dokmeci4, Manfung Yuen25, V G Mohan Prasad30, Osamu Yokosuka11, Ananta Prasad14, Priyanka Jain19, Irene Paulson19, Shiv Kumar Sarin19, Manoj Kumar Sahu20, Ayaskant Singh20, Ashok R Choudhury19

Background and Aim: Acute on Chronic Liver Failure (ACLF) is an evolving concept. There is scarce data on prognostication of ACLF cases mentioned in the literature. The present study was undertaken to find out the prognostic determinant in ACLF patients.

Materials and Methods: ACLF concept was defined as per Asian Pacific Association for the Study of Liver (APASL) consensus criteria 2014. Consecutive cases attending different centers in India and other Asian countries satisfying the above criteria were included and prospectively evaluated for three months.

Results: Out of total 2000 patients with ACLF (mean age: 36 years; M/F-1669:331), 30% and 44.25% patients died within 1 and 3 months respectively. Most of the deaths occurred in cases having acidosis [Adjusted odds ratio (AOR):30.04]; fever (AOR: 3.08); multiple organ failure (AOR: 1.95); cerebral failure (AOR: 1.44); renal failure (AOR: 1.4); prolonged ICU stay (AOR: 1.36); higher serum lactate (AOR: 1.17); higher serum bilirubin(AOR: 1.06); higher INR(PT) with AOR: 1.02; higher leukocyte count (AOR: 1.01); higher heart rate (AOR: 1.01). APASL ACLF Research Consortium (AARC score with AOR: 1.29) correlated better with early mortality compared to other prognostic scorings [SOFA (AOR: 1.11); MELD (AOR: 1.05); APACHAE (AOR: 1.04); CTP (AOR: 1.01); Glasgow coma scale (AOR: 0.95); CLIF SOFA (AOR: 0.92)].

 Conclusion: ACLF patients in Asian countries had high early (3 months) mortality with majority of death occurring in cases having acidosis, fever, and multiple organ failure. AARC scoring is the single most important prognostic determinant in prediction of early mortality in ACLF cases.

 

Characteristics and outcome of acute-on-chronic liver failure patients with hepatic encephalopathy

Guan Huei Lee1, Wah Wah Phyo1, Ashok Choudhury15, Jindal Ankur15, Rakhi Maiwall15, Manoj Kumar Sharma15, B.C Sharma15, Viniyendra Pamecha15, Mamun Mahtab5, S Rahman5, Yogesh Kumar Chawla17, Sunil Taneja17, Soek Siam Tan18, Harshad Devarbhavi21, Zhongping Duan7, Chen Yu7, Qin Ning23, Ji Dong Jia6, Deepak Amarapurkar8, C.E. Eapen11, Ashish Goel11, Saeed Hamid2, Amna Subhan Butt2, Wasim Jafri2, D.J. Kim10, Hasmik Ghazinian16, Ajit Sood12, L.A. Lesmana24, Abbas Zaigham19, Gamal Shiha13, Diana Payawal9, A.Kadir Dokmeci3, J.D. Sollano9, Gian Carpio9, G.K. Lau22, Fazal Karim20, P.N. Rao4, Richard Moreau14, P. Jain15, P. Bhatia15, G. Kumar15, Shiv Kumar Sarin15 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 10Center for Liver and Digestive Diseases, Chuncheon, Korea, Democratic People’s Republic of; 11Christian Medical College, India; 12Dayanand Medical College, India; 13Egyptian Liver Research Institute and Hospital, Egypt; 14Inserm, U1149, Centre de recherché sur l’Inflammation (CRI), UMR_S 1149, Labex INFLAMEX, Universite´ Paris Diderot Paris 7, France; 15Institute of Liver and Biliary Sciences (ILBS), India; 16Nork Clinical Hospital of Infectious Diseases, Armenia; 17Post Graduate Institute of Medical Education and Research, India; 18Selayang Hospital, Malaysia; 19Sindh Institute of Urology and Transplantation, Pakistan; 2Aga Khan University Hospital, Pakistan; 20Sir Salimur Rehman Medical College, Mitford Hospital, Bangladesh; 21St John Medical College, India; 22The Institute of Translational Hepatology, China; 23Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, China; 24University of Indonesia, Indonesia; 3Ankara University School of Medicine, Turkey; 4Asian Institute of Gastroenterology, India; 5Bangabandhu Sheikh Mujib Medical University, Bangladesh; 6Beijing Friendship Hospital, Capital Medical University, China; 7Beijing Youan Hospital, Capital Medical University, China; 8Bombay Hospital and Medical Research Centre, India; 9Cardinal Santos Medical Center, Philippines

Background: Acute-on-chronic liver failure (ACLF) is associated with high mortality. Hepatic encephalopathy (HE) has been identified as a negative prognostic factor. We examine the impact of HE on the outcome of ACLF patients in an Asian cohort.

Method: A total of 2,611 ACLF patients enrolled in the APASLACLF Research Consortium (AARC) database were analyzed. Clinical, laboratory and survival data of the patients were compared according to the degree of HE at the time of presentation.

Result: There are marked differences between ACLF subjects with HE (n = 1153) and without HE (n = 1458). 90-day mortality worsens significantly in relation to the presence (59.4% vs 31.3%, p\0.001) and grade of HE (Figure 1). HE is associated with sepsis, gastrointestinal bleed, and hepatitis C infection. Subjects with HE have lower hemoglobin and platelet levels, higher white cell count, urea/creatinine, bilirubin, INR, and transaminases. Prognostic scores, including MELD, SOFA, APACHE II and CLIF-SOFA scores, are consistently higher in ACLF patients with HE.

Conclusion: The presence and grade of HE identify a subgroup of ACLF patients with more severe disease and poorer prognosis.

Acute-on-Chronic Liver failure in Wilson’s disease—a series of 38 cases from APASL-ACLF research consortium (AARC)

Piyush Gupta1, Ashish Goel1, Chundamannil Eapen Eapen1, Ashok Kumar Choudhury5, Soek Siam Tan8, Guan Huei  Lee11, Seng Gee Lim11, Harshad Devarbhavi10, Yogesh Kumar Chawala7, Sunil Taneja7, Zhongping Duan3, Chen Yu4, Akash Shukla6, Padaki N Rao2, Zaigham Abbas9, Priyanka Jain5, Irene Paulson5, Shiv Kumar Sarin5 1christian Medical College, India; 10St John Medical College, India; 11Yong Loo Lin School of Medicine, Singapore; 2Asian Institute of Gastroenterology, India; 3Beijing You’an Hospital, Capital Medical University, China; 4Capital Medical University Beijing, China; 5Institute of Liver and Biliary Sciences, India; 6KEM Hospital and Seth GSMC, India; 7PGIMER, India; 8Selayang Hospital, Malaysia; 9Sindh Institute of Urology and Transplantation, Pakistan

Background: Acute-on-Chronic Liver Failure (ACLF) is a distinct syndrome with high short term mortality due to an acute hepatic insult leading to liver failure and subsequent extra-hepatic organ failure in a patient with chronic liver disease. Wilson’s disease flare in a back ground of the chronic disease may result in the syndrome of ACLF, but the data is sparse on this aspect. We analyzed Wilson disease presenting as ACLF from the AARC data base.

Method: 38 cases with Wilson disease, presented with ACLF (APASL definition) were recruited from March 2012 to July 2017. Data was obtained from multiple centres and aggregated on a common platform of AARC. Baseline parameters and further in-hospital course were followed until 90 days for death or liver transplant.

Result: Wilson disease constitutes 1.4% (38 of 2734) of ACLF with median age of 26 (7-73) years and 24 (63%) males. 14 ACLF cases had defined acute etiological insult (Group-A) and were aged 24 (7-73) years with 11 males. In rest of the 24 cases the etiology of the acute insult could not be defined (Group-B). They were aged 27 (11- 57) years with 14 males. All cases had index presentation as ACLF and were diagnosed as having Wilson disease subsequently. The etiology of acute insult was acute viral hepatitis in 7 cases (Hepatitis E in 3, Hepatitis A in 3, and Epstein - Barr virus in 1 case), drug induced liver injury in 5 cases (3 were on anti-tuberculosis therapy), sepsis and ethanol in 1 case each. 20 cases (8 in Group-A) had hepatic encephalopathy (HE) at baseline and 2 developed HE on day 4 (both from Group-A). The duration of jaundice was 0.75 (0.25-4.5) months with all patients having ascites at baseline. Median hospital stay was 24 (range 9-64) and 9 (range 1-36) days in group A and B respectively (p\0.001). The alkaline phosphatase-to-bilirubin ratio of\4 was observed in 9 cases (24%) whereas AST-to-ALT ratio was[2.2 in 17 cases (45%). The mortality with diagnosis of ACLF is higher (63.9%) against the overall mortality (43.8%) in AARC cohort due to ACLF [HR: 1.83, 95 CI%, 1.22-2.74, p = 0.003]. The mortality was (8/14) 57% for Group-A cases which was better than (16/22) 73% for Group-B cases (p\0.01), while 2 in Group B underwent liver

transplant.

Conclusion: This prospective dataset is the largest series of Wilson disease presenting as ACLF. Wilson disease patients with ACLF have a high mortality, which is much higher in absence of an identifiable precipitant for the same. This distinct syndrome needs new and early interventional strategies.

 

Higher baseline MAP protects against organ failure in patients of Acute on Chronic Liver Failure (ACLF)

Debi Prasad1, Ashok Kumar Choudhury Choudhury23, Mamun Al Mahtab Al Mahtab 6, A.Kadir Dokmeci4, Md. Fazal Karim32, Diana Alcantarapayawal11, Manfung Yuen31, V.G. Mohan36, George K. Lau20, Osamu Yokosuka12, Ananta Shrestha Prasad16, Priyanka Jain22, Irene Paulson23, Shiv Kumar Sarin22, Salimur Rahman Rahman6, Harshad Devarbhavi Devarbhavi33, Zhongping Duan9, Chen Yu8, Q Ning34, C E Eapen15, Ashish Goel Goel14, Y K Chawla30, Sunil Taneja Taneja29, R K Dhiman29, Ajay Duseja29, Saeed Sadiq Hamid3, Amna Subhan Butt2, Wasim Jafri2, Soeksiam Tan19, Dong Joon Kim18, Ji Dong Jia7, Deepak Narayan Amarapurkar10, Hasmik Ghazinian28, Jinhua Hu27, Guan Huei Lee37, Seng Gee Lim37, Laurentius A. Lesmana26, Cosmas Rinaldi Lesmana25, Akash Shukla24, Sombat Treeprasertsuk13, Samir Shah17, Chetan Kalal17, Zaigham Abbas38, Jose D Sollano35, Gian Carpio35, Manoj K Sahu21, P. N. Rao5 1University of Auckland, New Zealand; 10Bombay Hospital & Medical Research Center, Mumbai, India, India; 11Cardinal Santos Medical Center 10 Wilson St. Greenhills West San Juan City,, Philippines, Philippines; 12Chiba University, Japa; 13Chulalongkorn University,, Thailand; 14CMC VELLORE, India; 15CMC, Vellore, India, India; 16Foundation Nepal Sitapaila Height,, Nepal; 17Global Hospital, Mumbai, India, India; 18Hallym University College of Medicine, South Korea, Korea, Republic of; 19Hospital Selayang, Bata Caves, Selangor, Malaysia; 2Aga Khan University Hospital, Karachi, India; 20Humanity and Health Medical Group, China, China; 21IMS &SUM hospital, Odisa, India; 22Institute of Liver and Biliary Sciences Vasant Kunj, India; 23Institute of Liver and Biliary Sciences, Vasant Kunj, Delhi, India, India; 24KEM Hospital and Seth GSMC, India; 25Medistra Hospital, Jakarta, Indonesia, Indonesia; 26Medistra Hospital,, Indonesia, Indonesia; 27Millitary Hospital BeijingChina, China; 28Nork Clinical Hospital of Infectious Disease Armenia, Armenia; 29PGIMER, Chandigarh India, India; 3Aga Khan University Hospital,, Pakista; 30PGIMER, Chandigarh, India; 31Queen Mary Hospital, China, China; 32Sir Salimullah Medical College, Mitford Hospital Bangladesh, Bangladesh; 33St John Medical College, Bangalore, India, India; 34Tongji Hospital, Tongji Medical College, China; 35University of Santo Tomas, Manila, Philippines, Philippines; 36VGM Hospital Coimbatore, India, India; 37Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 38Ziauddin University Hospital, Karachi, Pakista; 4Ankara University School of Medicine, Turkey; 5Asian Institute of Gastroenterology Hyderabad, India; 6Bangabandhu Sheikh Mujib Medical university, Dhaka, Bangladesh, Bangladesh; 7Beijing Friendship Hospital, Capital University, China, China; 8Beijing You’an Hospital/Translational Hepatology Institute Capital Medical University, China; 9Beijing You’an Hospital/Translational Hepatology Institute Capital Medical University, India

Background: Acute on chronic liver failure (ACLF) is a frequently encountered syndrome associated with multi organ failure and high short term mortality. Shock on presentation, defined as MAP (mean arterial pressure)\60 mm Hg, is a predictor of mortality in ACLF. Little is known however about optimum MAP in ACLF without shock. We aim to compare survival data, complications and organ failure rate between patients with MAP 65-70 vs MAP[70.

Method: Patients with ACLF (APASL definition) were recruited from 52 centres across Asia Pacific. Data was prospectively collected in this observational study cohort from October 2012 to September 2017. Total 1436 patients were grouped into low MAP (65-70 mm Hg) and high MAP ([70 mmHg) and were analyzed with respect to organ failure, complications and 90 days surival. Patient with shock,acute variceal bleed or baseline renal failure were excluded. The primary end point was 90day survival and/or liver transplantation. Secondary endpoint was incidence of complications like AVB (Acute Variceal Bleeding), AKI (Acute kidney Injury), Sepsis and number of extrahepatic organ failures.

Result: Total of 1436 patients with 84% male and Mean age of 44 yrs were anaalyzed. Baseline characteristics like Age, sex, MELD, MELD Na and AARC score were similar between the groups. Majority of patients have ALD (51.9%), followed by viral hepatitis (24.4%), NASH (6.3%) and cryptogenic (8%) as aetiology of chronic liver disease. Incidence of AVB was statistically significant for higher MAP group (72.3% vs 43.8% p = 0.023). Number of Organ failure[2 was significant for lower MAP group vs higher MAP group (8.5% vs 2.4% with p = 0.005).No significant difference observed for sepsis and AKI incidence between the groups in the thirty day follow up period. Rate of liver transplant was not statistically significant between both groups. No difference in overall Survival on day 30 or day 90 between two groups. However time to event was shorter for lower MAP group (median survival 123 days vs 212 days). Interestingly cox proportional hazard ratio showed base line AARC score and age as significant predictors of 30 day and 90 day mortality. Other scores like MELD, MELD Na were not statistically significant predictor in our analysis

Conclusion: The baseline MAP above 70 is associated with fewer number of organ failures. Likely Higher MAP equals preserved PVR (peripheral vascular resistance) which leads to improved outcome in terms of organ failure irrespective of disease specific score like MELD Na, MELD and AARC scores at baseline.

 

Validation and comparison of AARC score in predicting mortality among patients with ACLF due to hepatitis E in Asia pacific Region

Amna Subhan Butt1, Saeed Hamid1, Ashok K Choudhury2, Wasim Jafri1, Y K Chawla3, Sunil Taneja3, Z Abbas4, Akash Shukla5, Mamun Al Mahtab 6, Deepak N Amarapurkar7, Md Fazal Karim8, C E Eapen9, Asish Goel9, Hasmik Ghaziniyan10, P N Rao11, Manoj K Sahu12, Samir Shah13, Chetan R Kalal13, Harshad Devarbhavi14, Z Duan15, Chen Yu15, S S Tan16, Diana A Payawal17, O Yokosuka18, Priyanka Jain2, Irene Paulson2, S K Sarin2, AARC APASL Working Party. 1. Aga Khan University Hospital, Karachi, Pakistan, 2. Institute of Liver and Biliary Sciences, New Delhi, India, 3. PGIMER, Chandigarh, India, 4. Ziauddin University Hospital, Karachi, Pakistan, 5. KEM Hospital and Seth GSMC, Mumbai, India, 6. Bangabandhu Sheikh Mujib Medical university, Dhaka,Bangladesh, 7. Bombay Hospital & Medical Research Centre, Mumbai, India, 8. Sir Salimullah Medical College, Mitford Hospital, Bangladesh, 9. Christian Medical College, Vellore, India, 10. Nork Clinical Hospital of Infectious Disease, Armenia, 11. Asian Institute of Gastroenterology, Hyderabad, India, 12. IMS &SUM hospital, Odisa, India, 13. Global Hospital, Mumbai, India, 14. St John Medical College, Bangalore, India, 15. Beijing You’an Hospital, Translational Hepatology Institute, Capital Medical University, 16. Departmentment of Hepatology, Hospital Selayang, Bata Caves, Selangor, Malaysia, 17. Cardinal Santos Medical Center, West San Juan City, Metro Manila, Philippines, 18. Chiba University, Japan

Background:Acute-on-chronic liver failure (ACLF) is a distinct entity, associated with high morbidity and mortality. Hepatitis E (HEV) is one of the leading causes of ACLF in Asia. Inclusion of smaller number of HEV related ACLF patients, differences in criteria to define ACLF and absence of validation studies questions the application of existing prognostic models for HEV related ACLF. The AARC-ACLF score has been developed using largest data base of 26 Asian countries and found superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week. However, AARC score has not been validated for HEV related ACLF. Hence, we aim to validate and compare the AARC score in predicting 30, 90 days mortality among patients with ACLF due to hepatitis E.

Methods:APASL-ACLF research consortium (AARC), consisting of 26 tertiary centers across Asia-Pacific regions, maintains an online database for patients diagnosed to have ACLF according to APASL criteria. All patients who had ACLF with acute hepatitis E were reviewed for the current study. The AARC score was validated and compared it with existing prognostic models AUROC.

Result:Out of 2897 patients with ACLF 230 (7.9%) had acute deterioration due to HEV. Mean age was 48.29±13.50 years and 83.9% were male. The most common cause of chronic liver disease was alcohol (26.5%) followed by cryptogenic cirrhosis (25.7%) and NASH (25.7%). Overall 62.2% survived & liver transplantation was done in 4.3% cases. Higher proportion of HE, AKI, organ failure, higher level of creatinine, bilirubin, INR, CTP, MELD, MELD-Na, SOFA, CILF-SOFA, AARC scores were observed among non-survivors as compared to survivors (Table 1). While validating AARC score to predict mortality in HEV related ACLF, The Hosmer– Lemeshow test showed good degree of fit. When we compared AARC score with various prognostic models, AARC score, MELD were found equivalent (AUROC 0.72) but superior to CTP, SOFA, CLIF SOFA, and APACHEE II predicting 30 days mortality (Figure 1). Similar trend was observed while predicting 90 days mortality.

Conclusion:The AARC score has been found equivalent to MELD score but superior to MELD-NA, CTP, SOFA, CLIF-SOFA and APACHEE predicting 30 and 90 days mortality in patients with HEV related ACLF in Asia pacific region. However, considering AUC 0.72 still there is a room to develop a prognostic model with higher accuracy for HEV-ACLF patients. Using such prognostic scores will help to stratify high risk patients on admission and to assess need of liver transplant.

 

 

AASLD 2018

Prevalence of metabolic risk factors and its impact on the severity and outcome of patients with alcohol related acute-on-chronic liver failure (ACLF) – A case control study from the AARC data base

Ajay Duseja, Arka De, Sunil Taneja, Ashok Kumar Choudhury2, Harshad Devarbhavi3, Jinhua Hu4, S S Hamid5, Amna S Butt5, Wasim Jafri5, Hasmik Ghazinyan6, Y K Chawla, R K Dhiman,  Z Duan7, Chen Yu7, S S Tan8, G H Lee9, S G Lim9, Dong Joon Kim10, Manoj Sahu11, J D Sollano12, Gian  Carpio12, V G Mohan Prasad13, Z Abbas14, Deepak N Amarapurkar15, L A Lesmana16, Cosmas Rinaldi Lesmana16, C E Eapen17, Ashish Goel17, Ajit Sood18, Vandana Midha18, Omesh Goyal18, A Kadir19, Q Ning20, Tao Chen20, Ke Ma20,   Diana A Payawal21, G K Lau22, Mamun Al Mahtab23, Salimur Rahman23, Mohd. Shahinul Alam23, Akash Shukla24,  Ananta Prasad25, Samir Shah26, Chetan Kalal26, , Guresh Kumar2, Priyanka Jain2, Irene Paulson2, Shiv K Sarin2, AARC working Party.

Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India 2Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, Delhi, India

3Department of Hepatology, St John Medical College, Bangalore, India 4Department of Medicine, 302 Millitary Hospital Beijing,China 5Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan 6Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Armenia

7Translational Hepatology Institute Capital Medical University, Beijing You’an Hospital

8Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia 9Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore 10Deparment of Internal Medicine, Hallym University College of Medicine, South Korea 11Department of Hepatology, IMS &SUM hospital, Bhuvaneswar, Odisa, India 12Department of Medicine, University of Santo Tomas, Manila, Philippines 13Department of Gastroenterology, VGM Hospital, Coimbatore, India 14Department of Medicine, Ziauddin University Hospital, Karachi 15Department of Hepatology, Bombay Hospital & Medical Research Center, Mumbai, India 16Department of Medicine, Medistra Hospital, Jakarta, Indonesia 17Department of Hepatology, CMC, Vellore, India 18Department of Gastroenterology, DMC, Ludhiana, India 19Department of Medicine, Ankara University School of Medicine, Turkey 20Department of Medicine, Tongji Hospital, Tongji Medical College 21Department of Medicine, Cardinal Santos Medical Center, Metro Manila, Philippines 22Department of Medicine, Humanity and Health Medical Group, Hong Kong 23Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh 24Department of Hepatology, KEM Hospital and Seth GSMC 25Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu 26Department of Hepatology, Global Hospital, Mumbai, India

Background – Presence of metabolic risk factors may have a bearing on patients with alcoholic liver disease. Impact of metabolic risk factors on the severity and outcome of patients with alcohol related acute-on-chronic liver failure (ACLF) is not known. Present study evaluated this effect in a large cohort of patients with alcohol related ACLF from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium [AARC] data base.

Methods – Patients prospectively enrolled with alcohol related ACLF defined as per the APASL definition in the AARC data base were included in this retrospective analysis. All patients had alcohol as the chronic insult with variable acute precipitating event (majority being alcoholic hepatitis). Metabolic risk factors were defined as the presence or absence of overweight or obesity, type 2 diabetes mellitus (type 2 DM), hypertension (HT) and dyslipidemia based on the average body weight, history of taking anti-diabetic, anti-hypertensive or anti-lipid drugs in last 5-10 years. Effect of metabolic risk factors on the severity and outcome of ACLF was assessed by comparing cases with these risk factors with a control group from the same cohort without any metabolic risk factor in terms of the severity of CTP, MELD and AARC score at presentation and 30 day and 90 day mortality.

Results – Of the total 2030 patients available in the AARC data base, alcoholic liver disease as the chronic component of ACLF was present in 1216 (60%) patients. Patients were predominantly males (98%) with a mean age of 42.5± 9.4 years and mean CTP, MELD and AARC score of 12± 1.4, 29.7 ± 7, 9.8 ± 2 respectively. Overall mortality was 392 (32%) at 30 days and 528 (43%) at 90 days. Information on the presence of overweight or obesity, type 2 DM, HT and dyslipidemia was available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. One hundred and fifty four (15%) patients had history of overweight or obesity, 142 (14%) patients had history of type 2 DM, 66 (7%) had history of HT and 141 (15%) patients had history of dyslipidemia. Eight hundred and nine (67%) patients did not have any of the risk factors and were taken as the control group. Patients with overweight or obesity had significantly higher MELD score (30.6 ± 7.1 vs 29.2± 6.9, p- 0.007) and those with dyslipidemia had higher AARC score (10.4 vs 1.2 vs 9.8 ± 2, p- 0.014) at presentation in comparison to the control group. None of the other risk factors either alone or in combination had any impact on the severity of ACLF. Presence of overweight or obesity was also significantly associated with increased 30-day mortality (HR 1.54, 95% C.I 1.06-2.24, p- 0.023) while none of the other risk factors, alone or in combination were associated with 30-day or 90 day mortality.

Conclusion – Presence of metabolic risk factors of overweight or obesity and dyslipidemia increase the severity of alcohol related ACLF at presentation. Presence of overweight or obesity also increases the short term risk of mortality in these patients.

 

 

Aarc Score Has Better Accuracy at Predicting 90-Day Mortality in Patients with Drug Induced Acute on Chronic Liver Failure (DILI-ACLF)

Dr. Karan Kumar 1 , Ashok Kumar Choudhury 2 , Mamun Al Mahtab 3 , Salimur Rahman 3 , Mohd Shahinul Alam3 , Harshad Devarbhavi 4 , Prof. Yogesh K. Chawla 5 , Prof. Ajay Duseja 5 , Prof. Radha K. Dhiman 5 , Dr. Sunil Taneja 5 , Prof. Qin Ning 6 , Ke Ma 7 , Tao Chen 7 , Zhongping Duan 8 , Yu Chen 8 , C E Eapen 9 , Ashish Goel 9 , Seok Siam Tan 10 , Saeed S. Hamid 11 , Amna Subhan Butt 11 , Syed Muhammad Wasim Jafri 11 , Dong Joon Kim12 , Jinhua Hu 13 , Ajit Sood 14 , Vandana Midha 14 , Omesh Goyal 14 , Akash Shukla 15 , Hasmik Ghazinian 16 , Manoj Sahu 17 , Dr. Sombat Treeprasertsuk 18 , Guan Huei Lee 19 , Seng Gee Lim20 , Laurentius A. Lesmana 21 , Cosmas Rinaldi Lesmana 21 , Samir Shah 22 , Chetan Ramesh Kalal 22 , Zaigham Abbas 23 , Jose D Sollano 24 , Gian Carpio 25 , V.G.Mohan Prasad 26 , Diana A. Payawal 27 , Abdulkadir Dokmeci 28 , Ananta Shrestha 29 , George K.K Lau 30 , Prof. Man-Fung Yuen 31 , Guresh Kumar 2 , Priyanka Jain 32 , Irene Paulson 2 , Prof. Shiv Kumar Sarin 2 and AARC Working Group, (1)Hepatology, Ilbs, (2)Department of Hepatology, Institute of Liver and Biliary Sciences, (3)Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, (4)Department of Gastroenterology, St John's Medical College Hospital, Bangalore, India, (5)Department of Hepatology, Postgraduate Institute of Medical Education and Research, (6)Tongji Hospital, (7)Medicine, Tongji Medical College, (8)Beijing Youan Hospital, Capital Medical University, (9)Chritian Medical College, (10)Department of Hepatology, Selayang Hospital, (11)The Aga Khan University, (12)Hallym University Medical Center, (13)Liver Failure Treatment and Research Center, 302 Military Hospital, (14)Dayanand Medical College and Hospital, (15)Seth GS Medical College & Kem Hospital, (16)Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, (17)Ism and SUM Hospital, (18)Medicine, Chulalongkorn University, (19)Division of Gastroenterology and Hepatology, National University Health System, Singapore, (20)Medicine, Yong Loo Lin School of Medicine, (21)Medicine, Medistra Hospital, (22)Hepatology, Global Hospital, (23)Department of Hepatogastroenterology, Ziauddin University, (24)Medicine, Santo Tomas, (25)University of Santo Tomas, (26)Vgm Hospital, (27)Cardinal Santos Medical Center, (28)Dept of Gastroenterology, Ankara University, (29)Foundation Nepal Sitapaila Height, (30)Humanity and Health Medical Centre, (31)Queen Mary Hospital, The University of Hong Kong, (32)Clinical Research, Institute of Liver and Biliary Sciences

Background: Of the various acute insults in Acute on chronic liver failure(ACLF) patients, Drug induced liver injury (DILI) is one of the major culprit. We compared disease severity and outcome in patients having DILI versus those with other acute hepatic insults causing ACLF. We analyzed the best predictive models of morbidity and mortality in these patients.

Methods: Consecutive ACLF patients, fulfilling the APASL definition of ACLF and prospectively enrolled in the APASL-ACLF Research Consortium (AARC) were included. Demography and outcome of those having Drugs as an acute insult (DILI-ACLF, Gr.I) were compared with the other patients (non-DILI ACLF, Gr.II). Various severity scores were compared with AARC score(consisting of 5 baseline variables- total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy) to predict mortality in those having Drug induced liver injury as an acute insult using Cox regression. Results: Of a total of 3,132 patients studied, 262 (8.4%) had Drugs as an acute insult. Among Drugs, Complementary and Alternative Medicines were major culprit (n, 5.6%) followed by Anti Tubercular drugs (n=2.8%). Mean age of patients in Gr.I and II were 47.35±13.75 and 44.22±12.21 years {p=ns}. In 28% of patients in Gr.I and in 6.6% of Gr.II, the etiology of underlying chronic disease remain unknown. Baseline MELD was higher in Gr.I patients(30.5±7.2) than Gr.II (28.6±7.02, p =0.002). At presentation, more patients in Gr.I than Gr.II (91.8% vs. 86.1% , p=0.003) had one or more organ failure {p=0.003}.However Renal Failure was seen in similar proportion in both group (27.9% v/s 29.4%) {p=ns} whereas sepsis was seen more in Gr.I than Gr.II(40.3%v/s 28.8%,p=0.002).30 day mortality was significantly higher in Gr. I than II (39.7% vs. 28.6%, p=0.004).The mean survival period was also lower in Gr.I than II (49.99 ±2.49 vs 58.94±0.74 days, p=0.005). Baseline MELD Score >30 predicted 90 days mortality with 69.2% sensitivity and 71 % specificity, whereas AARC score > 10.5 predicted 90 days mortality with 68.4% sensitivity and 73% specificity(p 0.001) . ROC comparing MELD,CTP,SOFA,CLIF-SOFA and AARC score at baseline revealed significantly higher area under curve for AARC score (0.75, p <0.001).

Conclusion: Patients with DILI-ACLF have poor outcome as compared to those having other causes of acute insults. Baseline AARC score of more than 10.5 has highest AUROC to predict 90 day mortality.

 

Hospital Readmission among Patients with Acute on Chronic Liver Failure (ACLF): Rate, reason, risk factor and impact on mortality

Priyanka Jain Ashok Kumar Choudhury, Mamun Al Mahtab2, Salimur Rahman2, Mohd. Shahinul Alam2, Harshad Devarbhavi3, Y K Chawla4, R K Dhiman4, Ajay Duseja4, Sunil Taneja4, Q Ning5,Tao Chen5, Ke Ma5,  Z Duan6, Chen Yu6, C E Eapen7, Ashish Goel7, S S Tan8, S S Hamid9, Amna S Butt9, Wasim Jafri9, Dong Joon Kim10, Jinhua Hu11, Deepak N Amarapurkar12, Ajit Sood13, Vandana Midha13, Omesh Goyal13, Akash Shukla14,Hasmik Ghazinyan15, Manoj Sahu16, Sombat Treeprasertsuk17, G H Lee18, S G Lim18, L A Lesmana19, Cosmas Rinaldi Lesmana19, Samir Shah20, Chetan Kalal20, Z Abbas21, J D Sollano22, Gian  Carpio22, V G Mohan Prasad23, Diana A Payawal24, A Kadir25, Ananta Prasad26, G K Lau27, M F Yuen28, Guresh Kumar, Irene Paulson, Shiv K Sarin, AARC working Party.

Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, Delhi, India

2Department of Hepatology, Bangabandhu Sheikh Mujib Medical university, Dhaka, Bangladesh 3Department of Hepatology, St John Medical College, Bangalore, India

4Department of Hepatology, PGIMER, Chandigarh, India 5Department of Medicine, Tongji Hospital, Tongji Medical College 6Translational Hepatology Institute Capital Medical University, Beijing You’an Hospital 7Department of Hepatology, CMC, Vellore, India

8Department of Medicine, Hospital Selayang, Bata  Caves, Selangor, Malaysia

9Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan

10Deparment of Internal Medicine, Hallym University College of Medicine

11Department of Medicine, 302 Millitary Hospital Beijing,China 12Department of Hepatology, Bombay Hospital & Medical Research Center, Mumbai, India 13Department of Gastroenterology, DMC, Ludhiana, India 14Department of Hepatology, KEM Hospital and Seth GSMC 15Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Armenia 16Department of Hepatology, IMS &SUM hospital, Bhuvaneswar, Odisa, India

17Department of Medicine, Chulalongkorn University, Bangkok, Thailand 18Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore 19Department of Medicine, Medistra Hospital, Jakarta, Indonesia 20Department of Hepatology, Global Hospital, Mumbai, India 21Department of Medicine, Ziauddin University Hospital,  Karachi

22Department of Medicine, University of Santo Tomas, Manila, Philippines 23Department of Gastroenterology, VGM Hospital, Coimbatore, India 24Department of Medicine, Cardinal Santos Medical Center, Metro Manila, Philippines 25Department of Medicine, Ankara University School of Medicine, Turkey 26Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu 27Department of Medicine, Humanity and Health Medical Group, Hong Kong 28Department of Medicine, Queen Mary Hospital Hong Kong, China

Background and aim: Acute on chronic liver failure is rapidly progressive liver failure and is associated with a significant rate of mortality. The hospital readmission rate of ACLF patients is a current issue. The aim of this study is to determine readmission rate, causes, association with mortality and predictors of readmission.

Methods and material: 3132 ACLF cases were enrolled across 30 centers from Oct, 2012 to May, 2018 in Asia pacific into APASL ACLF research consortium (AARC). On the study included 1241 ACLF cases with readmission details were analysed. Multivariate analysis was done for predicting of readmission and mortality at 90 days. Comparison was done by Conditional survival estimate (CSE) for one year mortality.

Results: Of 1241 patients, mean age of 43.8±11.3 with predominant male 89.6%; etiology of  acute insult: alcoholic hepatitis-61.2;HBV-10.9;DILI-11.1 and chronic insult: alcoholic-67.7;HBV-12.2;NASH-7.0, respectively, were observed. 843 (67.9%) had no readmission with mortality at 30,90,365days were 42.5%,50.3% and 51.5% respectively. However, 398(32.1) had at least one readmission with a median time to first readmission of 30 (5, 158) days and during a follow-up of 90 days, median number of readmission was 2 (2,10) with mortality at 90,365 days were 23.6% and 31.7%, respectively. By two week, one month and more than 1 year after discharge had readmission rate were 14.8%, 39.4% and 45.7% with mortality rate 23.4%, 52.3% and 24.2%, respectively. Patients with early readmission at two week and one month had subsequently higher risk of mortality (HR,95%CI,p) with (2.68,1.65-4.21,<0.001) and (4.08,2.45-6.8,<0.001),respectively compared to more than one month of 1st readmission. The causes of readmission were hepatic encephalopathy(HE)-52.8%,followed by ascites-45.0%, infection-34.7%,fever-19.6%, acute variceal bleed-10.1%. The cut off value of time to 1st readmission was 29.7 with AUROC-0.71, sensitivity-64.1, specificity-62.9. Predictor of time to first readmission included INR(1.34,1.17-1.62,<0.001), CTP score (1.17,1.03-1.32,0.001)and bilirubin (1.03,1.02-1.05,<0.001). Predictor of mortality at 90 days in readmission cohort were HE(1.85,1.07-3,15,0.03), early readmission≤30days(3.58,2.12-6.03,<0.001), Bilirubin (1.04,1.02-1.07,<0.001) and lactate (1.17,1.01-1.36,0.04). Figure-1 depicted conditional and actuarial survival between no readmission and readmission over time of one year. Conditional survival at different time point was nearly same in both groups after adjusting mortality at different time point.

Conclusion: Median time to 1st readmission of ACLF patients was 30 days and early readmission was highly associated with one year mortality. Predictors of 1st readmission were INR, bilirubin, CTP score. CSE provide information about dynamic prognostic change in survival over time. These findings support the need to develop of disease management intervention to present rehospitalisation.

 

 

Degree of Hemodynamic Derangements Correlate with Poor Outcomes in Acute on Chronic Liver Failure (ACLF) Patients

Dr. Vinay Kumar 1 , Ashok Kumar Choudhury 2 , Dr. Rakhi Maiwall 3 , Mamun Al Mahtab 4 , Salimur Rahman 4 , Mohd Shahinul Alam4 , Harshad Devarbhavi 5 , Prof. Yogesh K. Chawla 6 , Prof. Ajay Duseja 7 , Prof. Radha K. Dhiman 6 , Dr. Sunil Taneja 6 , Qin Ning 8 , Tao Chen 9 , Ke Ma 9 , Zhongping Duan 10 , Yu Chen 10 , C E Eapen 11 , Ashish Goel 11 , Seok Siam Tan 12 , Saeed S. Hamid 13 , Amna Subhan Butt 13 , Syed Muhammad Wasim Jafri 13 , Dong Joon Kim14 , Jinhua Hu 15 , Ajit Sood 16 , Vandana Midha 16 , Omesh Goyal 16 , Akash Shukla 17 , Hasmik Ghazinian 18 , Dr. Rajan V 1 , Dr. Vinod Arora 1 , Dr. Ankit Bhardwaj 19 , Manoj Sahu 20 , Dr. Sombat Treeprasertsuk 21 , Guan Huei Lee 22 , Seng Gee Lim23 , Laurentius A. Lesmana 24 , Cosmas Rinaldi Lesmana 24 , Samir Shah 25 , Chetan Ramesh Kalal 25 , Zaigham Abbas 26 , Jose D Sollano 27 , Gian Carpio 28 , V.G.Mohan Prasad 29 , Diana A. Payawal 30 , Abdulkadir Dokmeci 31 , Ananta Shrestha 32 , George K.K Lau 33 , Prof. Man-Fung Yuen 34 , Guresh Kumar 2 , Priyanka Jain 35 , Irene Paulson 2 , Prof. Shiv Kumar Sarin 2 and AARC Working Group, (1)Hepatology, Ilbs, (2)Department of Hepatology, Institute of Liver and Biliary Sciences, (3)Hepatology, Institute of Liver and Biliary Sciences, (4)Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, (5)Department of Gastroenterology, St John's Medical College Hospital, Bangalore, India, (6)Department of Hepatology, Postgraduate Institute of Medical Education and Research, (7)Postgraduate Institute of Medical Education & Research, (8)Huazhong University of Science and Technology, (9)Medicine, Tongji Medical College, (10)Beijing Youan Hospital, Capital Medical University, (11)Chritian Medical College, (12)Department of Hepatology, Selayang Hospital, (13)The Aga Khan University, (14)Hallym University Medical Center, (15)Liver Failure Treatment and Research Center, 302 Military Hospital, (16)Dayanand Medical College and Hospital, (17)Seth GS Medical College & Kem Hospital, (18)Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, (19)Clinical Research, Ilbs, (20)Ism and SUM Hospital, (21)Medicine, Chulalongkorn University, (22)Division of Gastroenterology and Hepatology, National University Health System, Singapore, (23)Medicine, Yong Loo Lin School of Medicine, (24)Medicine, Medistra Hospital, (25)Hepatology, Global Hospital, (26)Department of Hepatogastroenterology, Ziauddin University, (27)Medicine, Santo Tomas, (28)University of Santo Tomas, (29)Vgm Hospital, (30)Cardinal Santos Medical Center, (31)Dept of Gastroenterology, Ankara University, (32)Foundation Nepal Sitapaila Height, (33)Humanity and Health Medical Centre, (34)Queen Mary Hospital, The University of Hong Kong, (35)Clinical Research, Institute of Liver and Biliary Sciences

Background: With development of ACLF, the portal as well systemic hemodynamics alters in response to liver failure, systemic inflammatory response and sepsis. We investigated the changes in portal and systemic hemodynamics in patients with ACLF and their influence on organ failure and survival. Methods: Prospective enrolled ACLF patients as per APASL criteria into the AARC database and followedup for 90 days were included. Clinical events, laboratory parameters, disease severity indices and survival were analyzed. HVPG, mean Pulmonary Artery pressure (PAP), Pulmonary capillary wedge pressure (PCWP), Systemic (SVR) and Cardiac Output (CO) were compared to determine outcome.

Results: Hemodynamic data of 522 patients was analyzed. While high CO (8.23±4.2,p<0.019) correlated with 30 day mortality, SVR,MAP,PCWP and PAP were not associated. HVPG was associated with mortality(ROC- 0.66); HVPG >18 vs <18 mmHg was associated with increased variceal bleed risk and mortality [(14%vs5%) died at day 30(p<0.02) with (31.2%v/s 11.3%) had died at day 90(p<0.001)]. However HVPG >18 was not significantly associated with ascites at baseline or its worsening at day 30, or occurrence of sepsis or hepatic encephalopathy and patients with variceal bleed had poor outcome at day 90(p<0.011). Patients with severe alcoholic hepatitis (SAH) vs other etiologies, had worse outcome and high mortality at day30 (p<0.01). SAH patients had higher HVPG (19.2vs17.6± 5.74 mmHg, p<0.0001), cardiac output(8.88 vs. 6.98 L/min, p<0.001), PCWP(12.6 vs10 mmhg, p<0.002) and low SVR (910 vs 1137) dynes⋅sec⋅cm-5, p<0.005). Univariate analysis showed Urea (p<0.0001, 1.011(95%CI-1.005-1.017)), Bilirubin (p<0.0001, 1.057(1.0.0-1.085), Variceal bleed (p<0.001, 1.399, (1.150-1.703), HVPG>18 mmHg (p<0.0001, 2.820, (1.710-4.590), CO (p<0.023, 1.520(1.061-2.180)) as significant. In multivariate Analysis, HVPG>18(p<0.003,2.550,1.368-4.755), Urea(p<0.003,1.011,1.005-1.017), Bilirubin(P<0.025,1.037(1.015- 1.102), INR(P<0.023,1.379,(1.045-1.818) and Variceal bleed(p<0.05, 1.843(0.997-3.47)) significantly predicted poor outcome among the ACLF patients.

Conclusion: Our results shows the importance of degree of hemodynamic derangements as the basis for development of complications and mortality in patients of ACLF. High cardiac output and HVPG >18 mm Hg are significantly associated with increased risk of variceal bleed and mortality. These features were more pronounced in alcoholic hepatitis patients.

 

The Spectrum and Evolution of Severe Alcoholic Hepatitis in Large Prospective Cohort across Asia.

Irene Paulson, Ashok Kumar Choudhury, Dr. Saggere Murali Shasthry2, Harshad Devarbhavi3, Prof. Yogesh K. Chawla4, Prof. Ajay Duseja5, Prof. Radha K. Dhiman4, Dr. Sunil Taneja4, C E Eapen6, Ashish Goel6, Ajit Sood7, Vandana Midha7, Omesh Goyal7, Akash Shukla8, Dong Joon Kim9, Zhongping Duan10, Yu Chen10, Manoj Sahu11, V.G.Mohan Prasad12, Dr. Sombat Treeprasertsuk13, Seok Siam Tan14, Guan Huei Lee15, Seng Gee Lim16, Samir Shah17, Chetan Ramesh Kalal17, Saeed S. Hamid18, Amna Subhan Butt18, Syed Muhammad Wasim Jafri18, Ananta Shrestha19, Jose D Sollano20, Gian Carpio21, Zaigham Abbas22, Hasmik Ghazinian23, Abdulkadir Dokmeci24, Jinhua Hu25, Laurentius A. Lesmana26, Cosmas Rinaldi Lesmana26, Guresh Kumar, Priyanka Jain27, Prof. Shiv Kumar Sarin28 and AARC Working Group, (1)Department of Hepatology, Institute of Liver and Biliary Sciences, (2)Hepatology, Institute of Liver and Biliary Sciences, (3)Department of Gastroenterology, St John's Medical College Hospital, Bangalore, India, (4)Department of Hepatology, Postgraduate Institute of Medical Education and Research, (5)Postgraduate Institute of Medical Education & Research, (6)Chritian Medical College, (7)Dayanand Medical College and Hospital, (8)Seth GS Medical College & Kem Hospital, (9)Hallym University Medical Center, (10)Beijing Youan Hospital, Capital Medical University, (11)Ism and SUM Hospital, (12)Vgm Hospital, (13)Medicine, Chulalongkorn University, (14)Department of Hepatology, Selayang Hospital, (15)Division of Gastroenterology and Hepatology, National University Health System, Singapore, (16)Medicine, Yong Loo Lin School of Medicine, (17)Hepatology, Global Hospital, (18)The Aga Khan University, (19)Foundation Nepal Sitapaila Height, (20)Medicine, Santo Tomas, (21)University of Santo Tomas, (22)Department of Hepatogastroenterology, Ziauddin University, (23)Department of Hepatology, Nork Clinical Hospital of Infectious Diseases, (24)Dept of Gastroenterology, Ankara University, (25)Liver Failure Treatment and Research Center, 302 Military Hospital, (26)Medicine, Medistra Hospital, (27)Clinical Research, Institute of Liver and Biliary Sciences, (28)Department of Hepatology, Institute of Liver & Biliary Sciences

Background: Alcohol is one of the causes for liver damage extending from Severe Alcoholic Hepatitis(SAH) to Acute on chronic Liver Failure(ACLF). The study addresses the spectrum of ethanol related acute liver injury in the Asian Pacific region and predictors of outcome.

Methods: Alcoholic patients with jaundice,ascite,HE were grouped as SAH/ACLF from 40 centres in Asia(October 2012-May 2018). Analysis was done with respect to ascites,HE histologic evidence of cirrhosis,outcome in 3 month follow up and predictors by multivariate cox regression. ACLF was defined as per APASL definition and SAH was defined as recent history of jaundice and alcohol intake in a period of 4 weeks with MDF score>32.

Results: A total of 1572 patients;1510(69.06%)ACLF-Alcohol and 62(3.94%)SAH were analyzed. They were predominantly male(97.8% ;98.4%) and SAH was present in younger age(38.6±7.2 Vs. 42.9±9.3, p=<0.001). We analyzed ACLF cohort as subgroups with no ascites,no HE or presence of both. Absence of ascites and presenting as SAH at presentation(108,7.6%)was associated less organ failure(p<0.006), lesser occurrence of sepsis (32.3% Vs 20.8%, p=0.01) and lower mortality at day30(25.9% vs 32.6%,p=0.03), day90(35.2% Vs 42.9%, p=0.02) with comparable CTP,MELD. Absence of HE but presence of ascites (755,54.6%) was associated with less organ failure(p<0.001),lesser presentation with sepsis(33.7% Vs 27.9%, p=0.01) and lower mortality at day30(20.3% vs 47%,p<0.001) and day90 (32.8% Vs. 54%, p<0.001), but with higher CTP,MELD(p<0.001). No ascites or HE at presentaion who later developed APASL ACLF criteria, was noted in 63 cases(4.1%) and were compared with 62 cases of SAH. In multivariate analysis bilirubin was independent predictor of outcome(HR=1.13, 95CI 1.04-1.22,p=0.004), with a cut off 22.5mg/dl. SAH group was younger (38.6±7.3 Vs 43.1 ±9.2, p=0.03), with less histological evidence of cirrhosis(17.7% Vs.31.7%, p=0.03)with comparable DF Score(p=0.26),MELD score(p=0.23), sepsis at presentation(p=0.10) and comparable mortality(22% Vs 16%, p=0.13) at 90days. SAH presented with a lower MELD score(26.1±6.6 vs. 29.7±6.5, p<0.001)and low mortality [15(24.2%) Vs. 687(45.5%),p<0.001]. Alcoholic ACLF increases both 30(HR=2.1, 95CI 0.9-4.06,p= 0.03) and 90days(HR=2.56,95 CI1.37-4.78, p=0.003)mortality. Presence of ascites(HR=3.7, 95 CI 2.2-6.3; p=<0.001),HE (HR=2.5, 95 CI 2.1-2.9, p=<0.001), HE with ascites (HR=3.8, 95 CI 2.2-6.3; p=<0.001) further increases 90days mortality. 30 and 90days mortality of SAH was found to follow a steady trend with 14.5% and 16.1% respectively and nearly same trend among alcoholic ACLF with no ascites or HE at baseline(12.7%;22.2%).

Conclusion: This study defines evolution of liver injury i.e. SAH, ACLF with ascites and/or HE and those subsequently developed ACLF with increasing mortality. This necessitate to redefine the ethanol induce liver injury to prioritize intervention and prognostication.
 

 

ACHIEVMENTS

    • Total cases enrolled = 4279
    • Total centers across Asia = 50
    • Total manuscripts = 6
    • Total video conferences conducted = 37
    • Total abstract presented in conference by AARC group = 44