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. 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, 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: 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. Chawla1 , Sunil Taneja 1, Sahaj Rathi1, Amritangshu Borkakoty1, Ajay K. Duseja1, Shiv K. Sarin2; 1Hepatology, Post-graduate Institute of Medical Education and Research, Chandi-garh, India; 2Hepatology, 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 Choudhury1, 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 patient