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 �g/dl, p<0.001). Serum NH3 was higher in grade III-IV HE in Gr.A than Gr.B(145.7�72.7�g/dl vs.186�90.2�g/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 >140�g/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 >140�g/dl at any time point in first 7 days. HE grade III-IV and ammonia >140�g/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 >140�g/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% (score40) 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 .001; 90-day, 76.9, 56.0, and 26.4%, p.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 recherch� 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.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.001). The alkaline phosphatase-to-bilirubin ratio of4 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.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 1^st 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 1^st 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 1^st 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.
�

�

Antibiotics and steroids for 4-weeks in ACLF-AH with steroid response showed reduction of infections

Introduction

In this retrospective analysis we analysed whether oral antibiotics (cefixime) at discharge given for 1-week vs. 4-weeks in combination with steroids reduced infections in ACLF (alcoholic hepatitis).

�

Patient and methods

Retrospective database of APASL-AARC consortium was taken from April 2021- April 2022 and prospectively data was followed up for 6-months with patients of ACLF and having alcoholic hepatitis (steroid eligible) and received steroids for 28 days. Primary objective was to study infections at day 28. Secondary objectives were to study mortality at 28-day and 90 days; incidence of HRS; HE; AKI.

�

Results

1124 patients with ACLF collected during the period,534 patients (47.5%) having alcoholic hepatitis were screened;110 (20.59%) patients had received steroids(prednisolone 40mg for 4 weeks) of which 28 patients(25.4%) received oral cefixime(200mg/Bid for 4 weeks) while 82 patients(74.5%) received oral cefixime(200mg/Bid 7 days) along steroids. Incidence of AKI {6/28(21.42%) vs. 19/82(23.17%),P=1.00};UGIB{2/28(7.1%) vs. 9/82(10.9%),P= 0.72} were comparable. Incidence of infections at 28 days(5/28(17.8%) vs. 35/82(42.6%),P=0.02), repeated hospitalizations{3/28(10.7%) vs. 26/82(31.7%),P=0.04, mean number of hospitalized days (90-days){10� 3.4 vs 18 � 6.7},P=0.001 was lower in the 4-week arm.Incidence of pneumonia{7.1%(2/28) vs 21.9%(18/82), P=0.09),cellulitis {10.7%(3/28) vs 14.6% (12/82),P=0.75}, SBP {7.1%(2/28) vs 23.1%(19/82),P=0.09} was lower in the 4-week arm, not significant. Of steroid non responders {30/82(36.5%)};13/30 were continued on antibiotics suspecting subclinical infection showed lower infection rate requiring hospitalization {2/13(15.3%) vs. 9/17(52.9%),P=0.04}.Lower 28-day mortality was also noted in 4-week arm {2/28(7.1%) vs. 18/82(21.9%),P=0.09}.

Conclusions

4-week antibiotic-steroid therapy in steroid responder AH helped in reduction of severity of infections;duration of hospitalization;improved 4-week mortality.

�