Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update

Hepatology International - Tập 13 Số 4 - Trang 353-390 - 2019
Shiv Kumar Sarin1, Ashok Choudhury1, Manoj Kumar1, Rakhi Maiwall1, Mamun Al Mahtab2, Salimur Rahman2, Sanjiv Saigal3, Neeraj Saraf3, Arvinder S. Soin3, Harshad Devarbhavi4, Dong Joon Kim5, Shankar Prinja6, Ajay Duseja6, Sunil Taneja6, C. E. Eapen7, Ashish Goel7, Qin Ning8, Tao Chen9, Ke Ma8, Zhongping Duan9, Yú Chen9, Sombat Treeprasertsuk10, Saeed Hamid11, Amna S. Butt11, Wasim Jafri11, Akash Shukla12, Vivek A. Saraswat13, Soek Siam Tan14, Ajit Sood15, Vandana Midha15, Omesh Goyal15, Hasmik Ghazinyan16, Anil Arora17, Jinhua Hu18, Manoj Kumar Sahu19, Padaki Nagaraja Rao20, Guan Huei Lee21, Seng Gee Lim21, Laurentius A. Lesmana22, Cosmas Rinaldi Adithya Lesmana22, Samir Shah23, V. G. Mohan Prasad24, Diana A. Payawal25, Zaigham Abbas26, A. Kadir Dokmeci27, Jose D. Sollano28, Gian Carpio28, Ananta Shresta29, George Lau30, Md. Fazal Karim31, Gamal Shiha32, Rino Alvani Gani33, Kemal Fariz Kalista33, Man‐Fung Yuen34, Bikrant Bihari Lal35, Rajeev Khanna35, Vikrant Sood35, Viniyendra Pamecha36, Ankur Jindal1, V. Rajan1, Vinod Arora1, Osamu Yokosuka37, Madunil Anuk Niriella38, Hai Li39, Xiaolong Qi40, Atsushi Tanaka41, Satoshi Mochida42, Dominic Ray Chaudhuri43, Edward Gane43, Khin Maung Win44, Wei Ting Chen45, M Rela46, Dharmesh Kapoor23, Amit Rastogi3, Pratibha Kale47, Archana Rastogi48, Chhagan Bihari Sharma48, Meenu Bajpai49, Virender Singh6, Madhumita Premkumar6, Sudhir Maharashi50, A. Olithselvan51, Cyriac Abby Philips52, Anshu Srivastava53, Surender Kumar Yachha53, Zeeshan Ahmad Wani54, Thapa Br55, Anoop Saraya56, Raju Sharma56, Ashish Kumar17, Manav Wadhawan57, Subhash Gupta58, Kaushal Madan59, Puja Sakhuja60, Vivek Vij61, Barjesh Chander Sharma62, Hitendra Garg63, Vishal Garg63, Chetan Kalal64, Lovkesh Anand65, Tanmay Vyas66, Rajendra Prasad Mathur67, Guresh Kumar68, Priyanka Jain68, Samba Siva Rao Pasupuleti68, Yogesh Chawla69, Abhijit Chowdhury70, Shahinul Alam2, Do Seon Song71, Jin Mo Yang71, Eileen L. Yoon72
1Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, 110070, India
2Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
3Department of Hepatology, Medanta The Medicity, Gurgaon, India
4Department of Hepatology, St John Medical College, Bangalore, India
5Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea
6Department of Hepatology, PGIMER, Chandigarh, India
7Department of Hepatology, CMC, Vellore, India
8Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
9Translational Hepatology Institute Capital Medical University, Beijing You’ an Hospital, Beijing, China
10Department of Medicine, Chulalongkorn University, Bangkok, Thailand
11Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
12Department of Gastroenterology, Lokmanya Tilak Municipal General Hospital and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India
13Department of Gastroenterology, SGPGIMS, Lucknow, India
14Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia
15Department of Gastroenterology, DMC, Ludhiana, India
16Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia
17Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital and GRIPMER, New Delhi, Delhi, India
18Department of Medicine, 302 Millitary Hospital, Beijing, China
19Department of Gastroenterology and Hepatology Sciences, IMS & SUM Hospital, Bhubaneswar, Odisha, India
20Asian Institute of Gastroenterology, Hyderabad, India
21Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore
22Digestive Disease and GI Oncology Centre, Medistra Hospital, Jakarta, Indonesia
23Department of Hepatology, Global Hospitals, Mumbai, India
24Department of Gastroenterology, VGM Hospital, Coimbatore, India
25Fatima University Medical Center Manila, Manila, Philippines
26Department of Medicine, Ziauddin University Hospital, Karachi, Pakistan
27Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
28Department of Medicine, University of Santo Tomas, Manila, Philippines
29Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu, Nepal
30Department of Medicine, Humanity and Health Medical Group, New Kowloon, Hong Kong, China
31Department of Hepatology, Sir Salimullah Medical College, Dhaka, Bangladesh
32Egyptian Liver Research Institute And Hospital, Cairo, Egypt
33Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine, Cipto Mangunkusumo Hospital, Universitas Indonesia, Jakarta, Indonesia
34Department of Medicine, Queen Mary Hospital Hong Kong, The University of Hong Kong, Hong Kong, China
35Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
36Department of Hepatobilliary Pancreatic Surgery and Liver Transplant, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
37Professor Emeritus, Chiba University, Chiba, Japan
38Department of Medicine, University of Kelaniya, Ragama, Sri Lanka
39Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
40CHESS Frontier Center, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, China
41Department of Medicine, Tokyo University School of Medicine, Tokyo, Japan
42Department of Gastroenterology and Hepatology, Faculty of Medicine, Saitama Medical University, Saitama, Japan
43New Zealand Liver Transplant Unit, Auckland Hospital, Auckland, New Zealand
44Yangon GI and Liver Centre, Pabedan, Yangon, Myanmar
45Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
46Department of Liver Transplant Surgery, Dr. Rela Institute and Medical Centre, Chennai, India
47Department of Microbiology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
48Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
49Department of Immunohematology and Transfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, Delhi, India
50Department of Gatroenterology, SMS Med College, Jaipur, India
51Division of Liver Transplantation and Hepatology, Manipal Hospitals, Bangalore, India
52The Liver Unit, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, India
53Department of Pediatric Gastroenterology, SGPGIMS, Lucknow, India
54Noora Hospital in Srinagar, Shrinagar, India
55Department of Gastroenterology and Pediatric Gastroenterology, PGIMER, Chandigarh, India
56Department of Gastroenterology and Human Nutrition, AIIMS, New Delhi, India
57Department of Gastroenterology, Hepatology and Liver Transplant, B L K Hospital, New Delhi, India
58Centre for Liver and Biliary Science, Max Hospital, New Delhi, India
59Department of Gastroenterology, Hepatology and Liver Transplant, Max Hospital, New Delhi, India
60Department of Pathology, GB Pant Hospital, New Delhi, India
61Department of Liver Transplant and Hepatobilliary Surgery, Fortis Hospital, New Delhi, India
62Department of Gastroenterology, GB Pant Hospital, New Delhi, India
63Department of Gastroenterology, Hepatology and Liver Transplant, Apollo Hospital, New Delhi, India
64Department of Hepatology, Sir H N Reliance Hospital and Research Centre, Mumbai, India
65Department of Gastroenterology and Hepatology, Narayana Hospital, Gurugram, India
66Department of Hepatology, Parimal Multi-Speciality Hospital, Ahmedabad, India
67Department of Nephrology, Institute of Liver and Biliary Sciences, New Delhi, India
68Department of Statistics and Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
69Department of Hepatology and Gastroenterology, Kalinga Institute of Med Sciences, KIIT University, Bhubaneswar, India
70Department of Hepatology, Institute of Post Graduate Medical Education and Research, Kolkata, India
71Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
72Department Of Internal Medicine, Inje University College of Medicine, Busan, South Korea

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Sarin SK, Chandan K, Zaigham A, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2014;8:453–471

Sarin SK, Kumar A, et al. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009;3(269):282

Choudhury A, A Jindal SK, Sarin, for the APASL ACLF Working Party, et al. Liver failure determines the outcome in patients of Acute-on-Chronic Liver Failure (ACLF)-comparison of APASL-ACLF Research Consortium (AARC) and CLIF-SOFA model. Hepatol Int 2017;11(5):461–71

Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490

O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993;342:273–275

Jalan R, Pavesi M, Wendon J, CANONIC Study Investigators; EASLCLIF Consortium, et al. The CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure. J Hepatol 2015;62(4):831–840

Sen S, William R, Jalan R. The pathophysiological basis of acute-on- chronic liver failure. Liver 2002;22(Suppl 2):5–13

Wlodzimirow KA, Eslami S, Abu-Hanna A, et al. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality. Liver Int 2013;33(1):40–52

Bajaj JS, Moreau R, Kamath PS, Vargas HE, Arroyo V, Reddy KR, Szabo G, Tandon P, Olson J, Karvellas C, Gustot T, Lai JC, Wong F. Acute-on-chronic liver failure: getting ready for prime time? Hepatology 2018;68(4):1621–1632 PMID:29689120

Ferenci P, Lockwood A, Mullen K, et al. Hepatic encephalopathy- definition, nomenclature, diagnosis and quantification: final report of the working party at the 11th World Congress of Gastroenterology, Vienna 1998. Hepatology 2002;25(3):716–721

Moreau R, Jalan R, Gines P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013;144:1426–1437

Xu L, Tu Z, Xu G, et al. Epirubicin directly promotes hepatitis B virus (HBV) replication in stable HBV-expressing cell lines: a novel mechanism of HBV reactivation following anticancer chemotherapy. Mol Med Rep 2014;9(4):1345–1350

Mikulska M, Nicolini L, Signori A, et al. Hepatitis B reactivation in HBsAg negative/HBcAb positive allogeneic hematopoietic stem cell transplant recipients: risk factors and outcome. Clin Microbiol Infect 2014;15:8. https://doi.org/10.1111/1469-0691.12611

Pei R, Grund S, Verheyen J, et al. Spontaneous reactivation of hepatitis B virus replication in a HIV coinfected patient with isolated anti-hepatitis B core antibodies. Virol J 2014;11:9. https://doi.org/10.1186/1743-422X-11-9

Magalhaes RK, Ferreira D, Salgado M, et al. Hepatitis B virus reactivation after chemotherapy in an HIV positive patient. J Clin Gastroenterol 2013;47(6):565–566

Lim SG, Wai CT, Rajnakova A, Kajiji T, Guan R. Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B. Gut 2002;51(4):597–599

Martin ST, Cardwell SM, Nailor MD, Gabardi S. Hepatitis B reactivation and Rituximab: A new boxed warning and considerations for solid organ transplantation. Am J Transpl 2014. https://doi.org/10.1111/ajt.12649

Kusumoto S, Tanaka Y, Mizokami M, Ueda R. Strategy for preventing hepatitis B reactivation in patients with resolved HBV infection following rituximab containing chemotherapy. Hepatology 2013. https://doi.org/10.1002/hep.26963

Tsutsumi Y, Yamamoto Y, Shimono J, Ohhigashi H, Teshima T. Hepatitis B virus reactivation with rituximab containing regimen. World J Hepatol 2013;5(11):612–662

Huang M, Huang L. Reactivation of hepatitis C viral infection after treatment with infliximab. J Clin Gastroenterol 2014;48(2):189–190

Sagnelli E, Pisaturo M, Stanzione M, Messina V, Alessio L, Sagnelli C, et al. Clinical presentation, outcome and response to therapy among patients with acute exacerbation of chronic hepatitis C. Clin Gastroenterol Hepatol 2013;11(9):1174–1180

Radha Krishna Y, Saraswat VA, Das K, Himanshu G, Yachha SK, Aggarwal R, Choudhari G. Clinical features and predictors of outcome in acute hepatitis A and hepatitis E virus hepatitis on cirrhosis. Liver Int 2009;29(3):392–398

Mahtab MA, Rahman S, Khan M, Karim MF. Hepatitis E virus is a leading cause of acute-on-chronic liver disease: experience from a tertiary center in Bangladesh. Hepatobiliary Pancreat Dis Int 2009;8(1):50–52

Kumar M, Sharma BC, Sarin SK. Hepatitis E virus as an etiology of acute exacerbation of previously unrecognized asymptomatic patients with hepatitis B virus related chronic liver disease. J Gastroenterol Hepatol 2008;23(6):83–87

Acharya SK, Sharma PK, Singh R, Mohanty SK, Madan K, Jha JK, et al. Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death. J Hepatol 2007;46:387–394

Kim AY, Chung RT. Bacterial, Parasitic and Fungal infections of the liver, including liver abscess. In: Feldman M, Friedman L, Brandt LJ, editors. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 9th ed. Philadelphia: WB Saunders; 2010. 1351

Moreau R, Arroyo V. Acute-on-chronic liver failure: a new clinical entity. Clin Gastroenterol Hepatol 2014. https://doi.org/10.1016/j.cgh.2014.02.027 .

Garg H, Kumar A, Garg V, Sharma P, Sharma BC, Sarin SK. Clinical profile and predictors of mortality in patients of acute-on-chronic liver failure. Dig Liver Dis 2012;44(2):166–171

Wasmuth HE, Kunz D, Yagmur E, Timmer-Stranghöner A, Vidacek D, Siewert E, et al. Patients with acute-on-chronic liver failure display “sepsis- like” immune paralysis. J Hepatol 2005;42(2):195–201

Duseja A, Chawla YK, Dhiman RK, Kumar A, Choudhary N, Taneja S. Non-Hepatic insults are common precipitants in patients with acute-on-chronic liver failure. Dig Dis Sci 2010;55(11):3188–3192

Lo Re V III, Carbonari DM, Lewis JD, et al. Oral azole antifungal medications and risk of acute liver injury, overall and by chronic liver disease status. Am J Med 2016;129:283–291

Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN Prospective Study. Gastroenterology 2015;148:1340–1352

Watkins PB, Seligman PJ, Pears JS, et al. Using controlled clinical trials to learn more about acute drug-induced liver injury. Hepatology 2008;48:1680–1689

Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis—a practical guide. Aliment Pharmacol Ther 2013;37:1132–1156

Tarantino G, Conca P, Basile V, et al. A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease. Hepatol Res 2007;37:410–415

Pais R, Rusu E, Ratziu V. The impact of obesity and metabolic syndrome on chronic hepatitis B and drug-induced liver disease. Clin Liver Dis 2014;18:165–178

Hoffmann CJ, Charalambous S, Thio CL, et al. Hepatotoxicity in an African antiretroviral therapy cohort: the effect of tuberculosis and hepatitis B. Aids 2007;21:1301–1308

Thulstrup AM, Molle I, Svendsen N, et al. Incidence and prognosis of tuberculosis in patients with cirrhosis of the liver. A Danish nationwide population based study. Epidemiol Infect 2000;124:221–225

Lin YT, Wu PH, Lin CY, et al. Cirrhosis as a risk factor for tuberculosis infection–a nationwide longitudinal study in Taiwan. Am J Epidemiol 2014;180:103–110

Wang N-T, Huang Y-S, Lin M-H, Huang B, Perng C-L, Lin H-C. Chronic hepatitis B infection and risk of antituberculosis drug-induced liver injury: systematic review and meta-analysis. J Chin Med Assoc 2016;79:368–374

Kim WS, Lee SS, Lee CM, Kim HJ, Ha CY, Kim HJ, et al. Hepatitis C and not Hepatitis B virus is a risk factor for anti-tuberculosis drug induced liver injury. BMC Infect Dis 2016;16:50

Qin G, Shao JG, Zhu YC, et al. Population-representative incidence of acute-on-chronic liver failure. A prospective cross-sectional study. J Clin Gastroenterol 2016;50:670–675

Shi Y, Yang Y, Hu Y, et al. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 2015;62:232–242

Shalimar, Saraswat V, Singh SP, et al. Acute-on-chronic liver failure in India: the Indian National Association for Study of the Liver consortium experience. J Gastroenterol Hepatol 2016;31:1742–1749

Yeoman AD, O’Grady JG, Heneghan MA. Prognosis of acute severe autoimmune hepatitis (AS-AIH): the role of corticosteroids in modifying outcome. J Hepatol 2014;61:876–882

Stravitz RT, Lefkowitch JH, Fontana RJ, Gershwin ME, Leung PS, Sterling RK, et al. Autoimmune acute liver failure: proposed clinical and histological criteria. Hepatology 2011;53:517–526

Anand L, Choudhury A, Bihari C, Sarin SK, for APASL ACLF (AARC) working party. Flare of Autoimmune Hepatitis causing acute on chronic liver failure (ACLF): diagnosis and response to corticosteroid therapy. Hepatology 2018. https://doi.org/10.1002/hep.30205 (Epub ahead of print, PMID: 30113706 )

Ripoll C, Groszmann R, Garcia-Tsao G, Grace N, Burroughs A, Planas R, et al. Hepatic pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterol 2007;133:481–488

Amitrano L, Guardascione MA, Martino R, Manguso F, Menchise A, Balzano A. Hypoxic hepatitis occurring in cirrhosis after variceal bleeding: still a lethal disease. J Clin Gastroenterol 2012;46(7):608–612

Bruns T, Zimmermann HW, Stallmach A. Risk factors and outcome of bacterial infections in cirrhosis. World J Gastroenterol 2014;20(10):2542–2554

Kim RD, Kim JS, Watanabe G, Mohuczy D, Behrns KE. Liver regeneration and the atrophy-hypertrophy complex. Semin Interv Radiol 2008;25:92–103

Langlet P, Escolano S, Valla D, Coste-Zeitoun D, Denie C, Mallet A, et al. Clinicopathological forms and prognostic index in Budd–Chiari syndrome. J Hepatol 2003;39:496–501

Desmet VJ, Roskams T. Cirrhosis reversal: a duel between dogma and myth. J Hepatol 2004;40:860–867

Wanless IR, Wong F, Blendis LM, Greig P, Heathcote EJ, Levy G. Hepatic and portal vein thrombosis in cirrhosis: possible role in development of parenchymal extinction and portal hypertension. Hepatology 1995;21(5):1238–1247

Kim MY, Cho MY, Baik SK, Park HJ, Jeon HK, Im CK, et al. Histological subclassification of cirrhosis using the Laennac fibrosis scoring system correlates with clinical stage and grade of portal hypertension. J Hepatol 2011;55(5):1004–1009

Rastogi A, Maiwall R, Bihari C, Ahuja A, Kumar A, Singh T, et al. Cirrhosis etiology and laennac staging system correlate with high portal pressure. Histopathology 2013;62(5):731–741

Libbrecht L, Desmet V, Van Damme B, Roskams T. Deep intralobular extension of human hepatic “progenitor cells” correlates with parenchymal inflammation in chronic viral hepatitis: can “progenitor cells” migrate? J Pathol 2000;192:373–378

de Graaf EL, Kench J, Dilworth P, Shackel NA, Strasser S, Joseph D, et al. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the donor risk index. J Gastroenterol Hepatol 2012;27(3):540–546

Gabrielli M, Moisan F, Vidal M, Duarte I, Jiménez M, Izquierdo G, et al. Steatotic livers. Can we use them in OLTX? Outcome data from a prospective baseline liver biopsy study. Ann Hepatol 2012;11(6):891–898

Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999;30(6):1356–1362

Loomba R, Sanyal A. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol 2013;10(11):686–690

Laleman W, Verbeke L, Meersseman P, Wauters J, van Pelt J, Cassiman D, et al. Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions. Expert Rev Gastroenterol Hepatol 2011;5(4):523–537

Rastogi A, Kumar A, Sakhuja P, Bihari C, Gondal R, Hissar S, et al. Liver histology as predictor of outcome in patients with acute-on-chronic liver failure (ACLF). Virchows Arch 2011;459(2):121–127

Kalambokis G, Manousou P, Vibhakorn S, Marelli L, Cholongitas E, Senzolo M, et al. Transjugular liver biopsy–indications, adequacy, quality of specimens, and complications—a systematic review. J Hep 2007;47:284–294

Myers RP, Elkashab M, Ma M, et al. Transient Elastography for noninvasive assessment of liver fibrosis: a multicenter Canadian study. Can J Gastroenterol 2010;24(11):661–670

Kedarisetty CK, Bhardwaj A, Garg H, Wagle P, Sarin SK. Reduction in liver stiffness at one month is a predictor of survival in acute-on-chronic liver failure. In: Presented as poster at APASL annual conference 2014, Brisbane

Jha AK, Nijhawan S, Rai RR, Nepalia S, Jain P, Suchismita A. Etiology, clinical profile and inhospital mortality of acute-on-chronic liver failure: a prospective study. Indian J Gastroenterol 2013;32(2):108–114

Seto WK, Lai CL, Yuen MF. Acute-on-chronic liver failure in chronic hepatitis B. J Gastroenterol Hepatol 2012;27(4):662–669

Adams LA, Lymp JF, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population based cohort study. Gastroenterology 2005;129:113–121

Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and natural history of nonalcoholic fatty liver disease. J Hepatol 2004;40:578–584

Bhala N, Angulo P, Van der Poorten D, Lee E, Hui JM, Saracco G, Adams LA, et al. The Natural history of Nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology 2011;54:1208–1216

Sheth SG, Flamm SL, Gordon FD, Chopra S. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol 1998;93(1):44–48

Kruger FC, Daniels CR, Kidd M, Swart G, Brundyn K, van Rensberg C, Kotze M. APRI: a simple bedside marker of advanced fibrosis that can avoid liver biopsy in patients with NAFLD/NASH. S Afr Med J 2011;101(7):477–480

Berzigotti A, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Morillas R, Portal Hypertension Collaborative Group, et al. Obesity is an independent risk factor for clinical decompensation in patients with cirrhosis. Hepatology. 2011;54:555–561

Duseja A, De A, Taneja S, Choudhury A, Devarbhavi H, Hu J, et al. 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. AASLD abstract. Hepatol 2018;S1

Choudhury AK, Mahtab AM, Sarin SK, for ACLF Working Party. Acute on Chronic Liver Failure (ACLF) has a better long-term survival than Acute decompensation- a study of 4897 patients from APASL ACLF Research Consortium (AARC) with a follow-up of 5 years. AASLD abstract. Hepatol 2017;S1

Choudhury A, Kumar M, Sarin SK, APASL ACLF working party. Systemic inflammatory response syndrome in acute on chronic liver failure- relevance of ‘Golden Window’—a prospective study. J Gastroenterol Hepatol 2017;32(12):1989–1997. https://doi.org/10.1111/jgh.13799 (PMID: 28374414)

Katoonizadeh A, Laleman W, Verslype C, Wilmer A, Maleux G, Roskams T, Nevens F. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010;59(11):1561–1569

Jalan R, Mookerjee RP. Acute-on-chronic liver failure: an early liver biopsy is essential? Gut 2010;59(11):1455–1456

Hoffman A, Rahman F, Prengel S, Schuchmann M, Gotz M, Moehler M, Galle PR, Li Z, Kalloo AN, Kiesslich R. Mini-laparoscopy in the endoscopy unit: safety and outcomes in over one thousand patients. World J Gastrointest Endosc 2011;3(1):6–10 PMID: 21258600

Katoonizadeh A, Laleman W, Verslype C, Wilmer A, Maleux G, Roskams T, Nevens F. Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study. Gut 2010;59(11):1561–1569

Rastogi A, Maiwall R, Bihari C, Trehanpati N, Pamecha V, Sarin SK. Two-tier regenerative response in liver failure in humans. Virchows Arch 2014;464(5):565–573

Rastogi A, Bihari C, Maiwall R, Ahuja A, Sharma MK, Kumar A, Sarin SK. Hepatic stellate cells are involved in the pathogenesis of acute-on-chronic liver failure. Virchows Arch 2012;461(4):393–398

Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, et al. Granulocyte colony stimulating factor mobilizes CD 34 + cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology 2012;142(3):505–512

Saxena P, Bihari C, Rastogi A, Agarwal S, Anand L, Sarin SK. Sonoclot signature analysis in patients with liver disease with conventional coagulation studies. Adv Hematol 2013;2013:23751

New York Heart Association Inc. New York Heart Association Classification of Heart Failure. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis. 6th ed. Boston: Little Brown; 1964. 114

Jeppesen JB, Mortensen C, Bendtsen F, Møller S. Lactate metabolism in chronic liver disease. Scand J Clin Lab Invest 2013;73(4):293–299

Cardoso NM, Silva T, Basile-Filho A, Mente ED, Castro-e-Silva O. A new formula as a predictive score of post-liver transplan- tation outcome: postoperative MELD-lactate. Transpl Proc 2014;46(5):1407–1412

Cordoba J, Ventura-Cots M, Simón-Talero M, Amorós A, Pavesi M, Vilstrup H, Angeli P, Domenicali M, Ginés P, Bernardi M, Arroyo V, CANONIC Study Investigators of EASL-CLIF Consortium. Char-acteristics, risk factors, and mortality of cirrhotic patients hospital-ized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol 2014;60(2):275–281

Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 2003;31:1250–1256

Gustot T, Felleiter P, Pickkers P, Sakr Y, Rello J, Velissaris D, et al. Impact of infection on the prognosis of critically ill cirrhotic patients: results from a large worldwide study. Liver Int 2014;7:15. https://doi.org/10.1111/liv.12520 .

Arvaniti V, D’Amico G, Fede G, Manousou P, Tsochatzis E, Plequezuelo M, Burroughs AK. Infections in patients with cirrhosis increase mortality four- fold and should be used in determining prognosis. Gastroenterology 2010;139:1246–1256

Hoque R, Farooq A, Mehal WZ. Sterile inflammation in the liver and pancreas. J Gastroenterol Hepatol 2013;28:61–67

Chovatiya R, Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol Cell 2014;54:281–288

Thabut D, Massard J, Moreau R, et al. Model for end-stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure. Hepatology 2007;46:1872–1882

Jalan R, Stadlbauer V, Sen S, Cheshire L, Chang YM, Mookerjee RP. Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study. Crit Care 2012;16(6):R227

Granja C, Póvoa P, Lobo C, Teixeira-Pinto A, Carneiro A, Costa-Pereira A. The predisposition, infection, response and organ failure (Piro) sepsis classification system: results of hospital mortality using a novel concept and methodological approach. PLoS One 2013;8(1):e53885. https://doi.org/10.1371/journal.pone.0053885

Hotchkiss RS, Monneret G, Payen D. Sepsis induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol 2013;13(12):862–874

Duseja A, Chawla YK, Dhiman RK, Kumar A, Choudhary N, Taneja S. Non-hepatic insults are common precipitants in patients with acute-on-chronic liver failure. Dig Dis Sci 2010;55(11):3188–3192

Khanam A, Trehanpati N, Garg V, Kumar C, Garg H, Sharma BC, Sarin SK. Altered frequencies of dendritic cells and IFN- γ secreting T cells with granulocyte colony stimulating factor (GCSF) therapy in acute-on-chronic liver failure. Liver Int 2014;34(4):505–513

Kox WJ, Volk T, Kox SN, Volk HD. Immunomodulatory therapies in sepsis. Intensive Care Med 2000;26(Suppl 1):S124–S128

Wasmuth HE, Kunz D, Yagmur E, Timmer- Stranghöner A, Vidacek D, Siewert E, et al. Patients with acute-on-chronic liver failure display “sepsis- like” immune paralysis. J Hepatol 2005;42(2):195–201

Jindal A, Sarin SK. Acute Kidney Injury (AKI) at admission and its response to terlipressin as a predictor of mortality in patients with acute-on-chronic liver failure (ACLF). J Hepatol 2013;58(S1):S89

Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med 2009;361:1279–1290

Martín-Llahí M, Guevara M, Torre A, Fagundes C, Restuccia T, Gilabert R, et al. Prognostic importance of the cause of renal failure in patients with cirrhosis. Gastroenterology 2011;140:488–496

Stadlbauer V, Wright G, Banaji M, Mukhopadhyay A, Mookerjee R, Moore K, et al. Relationship between activation of the sympathetic nervous system and renal blood flow autoregulation in cirrhosis. Gastroenterology 2008;134:111–119

Kumar A, Das K, Sharma P, Mehta V, Sharma BC, Sarin SK. Hemodynamic studies in acute-on-chronic liver failure. Dig Dis Sci 2009;54(4):869–878. https://doi.org/10.1007/s10620-008-0421-9 .

Cárdenas A, Ginès P. Acute-on-chronic liver failure: the kidneys. Curr Opin Crit Care 2011;17(2):184–189

Maiwall R, Sarin SK, Kumar S, for APASL ACLF Research Consortium (AARC) working party, et al. Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure. Liver Int 2017. https://doi.org/10.1111/liv.13443 (Epub ahead of print, PMID: 28393476)

Maiwall R, Kumar S, Vashishtha C, Kumar M, Garg H, Nayak SL, et al. Acute kidney injury (AKI) in patients with Acute-on-chronic Liver failure (ACLF) is different from patients with cirrhosis. Hepatology 2013;58(4 Suppl):36A–91A

Wan ZH, Wang JJ, You SL, Liu HL, Zhu B, Zang H, et al. Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure. World J Gastroenterol 2013;19(48):9432–9438

Xing T, Zhong L, Chen D, Peng Z. Experience of combined liver-kidney transplantation for acute-on-chronic liver failure with renal dysfunction. Transpl Proc 2013;45(6):2307–2313

Maiwall R, Chandel SS, Wani Z, Kumar S, Sarin SK. SIRS at admission is a predictor of AKI development and mortality in hospitalized patients with severe alcoholic hepatitis. Dig Dis Sci 2016;61(3):920–929

Arora V, Maiwall R, Choudhury A, Jain P, Kumar G, Sarin SK. Terlipressin is superior to Noradrenaline in the management of acute kidney injury (AKI) in patients with ACLF. Terlipressin is superior to Noradrenaline in the management of acute kidney injury (AKI) in patients with ACLF. J Hepatol 2017;66(1):S563 (in press)

Gonwa TA, Wadei HM. The challenges of providing renal replacement therapy in decompensated liver cirrhosis. Blood Purif 2012;33:144–148

Cardoso FS, Gottfried M, Tujios S, Olson JC, Karvellas CJ, US Acute Liver Failure Study Group. Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology 2017;31:15. https://doi.org/10.1002/hep.29488 (Epub ahead of print)

Donovan JP, Schafer DF, Shaw BW Jr, Sorrell MF. Cerebral edema and increased intracranial pressure in chronic liver disease. Lancet 1998;351:719–721

Gupta T, Dhiman RK, Ahuja CK, Agrawal S, Chopra M, Kalra N, Duseja A, Taneja S, Khandelwal N, Chawla Y. Characterization of cerebral edema in acute-on chronic liver failure. J Clin Exp Hepatol 2017;7:190–197.

Butterworth RF, McPhail MJW. L-ornithine L-aspartate (LOLA) for hepatic encephalopathy in cirrhosis: results of randomized controlled trials and meta-analyses. Drugs 2019;79(Suppl 1):31–37

Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, et al. Infection and systemic inflammation, not ammonia, are associated with grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol 2011;54:640–649

Guevara M, Baccaro ME, Torre A. Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: a prospective study with time-dependent analysis. Am J Gastroenterol 2009;104:1382–1389

Verma A, Choudhury AK, Sarin SK, for APASL ACLF Working party, et al. 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. AASLD abstract. Hepatol 2017;S1

Tripodi A, Primignani M, Chantarangkul V, Dell’Era A, Clerici M, de Franchis R, et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009;137:2105–2111

Caldwell SH, Hoffman M, Lisman T, Macik BG, Northup PG, Reddy KR, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology 2006;44:1039–1046

Blasi A, Calvo A, Prado V, Reverter E, Carlos Reverter J. Hernández-Tejero M Coagulation failure in patients with Acute-on-Chronic Liver Failure (ACLF) and decompensated cirrhosis: beyond INR. Hepatology 2018. https://doi.org/10.1002/hep.30103

Fisher C, Patel VC, Stoy SH, Singanayagam A, Adelmeijer J, Wendon J, et al. Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on-chronic-liver failure. J Crit Care 2018;43:54–60

Montalto P, Vlachogiannakos J, Cox DJ, Pastacaldi S, Patch D, Burroughs AK. Bacterial infection in cirrhosis impairs coagulation by a heparin effect: a prospective study. J Hepatol 2002;37:463–470

Noris M, Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies? Blood 1999;94:2569–2574

Premkumar M, Saxena P, Mirza R, Baweja S, Sharma CB, Choudhury AK, Kedarisetty CK, Sarin SK. Assessment and relevance of coagulation disorders in patients with acute-on-chronic liver failure during Systemic Inflammatory Response (SIRS) and development of sepsis. Liv Int.2018. https://doi.org/10.1111/liv.14034 (accepted)

Blasi A, Calvo A, Prado V, Reverter E, Carlos Reverter J, Hernández-Tejero M, Aziz F, Amoros A, Cardenas A, Fernández J. Coagulation failure in patients with Acute-on-Chronic Liver Failure (ACLF) and decompensated cirrhosis: beyond INR. Hepatology 2018. https://doi.org/10.1002/hep.30103

Premkumar M, Saxena P, Mirza R, Jain P, Bhatia P, Kumar G, Sukriti S, Bihari C, Choudhury A, Sarin SK. Heparin like effect increases risk of mortality and bleeding tendency in patients with severe alcoholic hepatitis during systemic Inflammatory Response (SIRS) and sepsis. AASLD abstract. Hepatol 2017;S1

Wells PS, Anderson DR, Rodger M, Forgie M, Kearon C, Dreyer J, Kovacs G, Mitchell M, Lewandowski B, Kovacs MJ. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003;349(13):1227–1235 PubMed PMID: 14507948

Garg H, Kumar A, Garg V, Kumar M, Kumar R, Sharma BC, et al. Hepatic and systemic hemodynamic derangements predict early mortality and recovery in patients with acute-on-chronic liver failure. J Gastroenterol Hepatol 2013;28(8):1361–137

Kumar V, Choudhury AK, Maiwall R, Mahtab MA, Rahman S, Alam MS, et al. Degree of hemodynamic derangements correlate with poor outcomes in acute on chronic liver failure (ACLF) patients. AASLD abstract. Hepatol 2018;S1

Choudhury AK, Sharma MK, Maiwal R, Jain P, Mahtab MA, Chawla YK, et al. Portal hemodynamics predicts the outcome in severe alcoholic hepatitis presenting as acute-on-chronic liver failure. J Hepatol 2016;S1:64–306

Kainth S, Kumar M, Choudhury AK, Anand L, Jindal A, Kumar G, et al. Efficacy and safety of carvedilol in patients of acute-on-chronic liver failure with small or no esophageal varices—a placebo control open label randomised trial (NCT02583698). Hepatology 2017;66(Suppl 1):83A

Hari A, Nair HK, De Gottardi A, Baumgartner I, Dufour JF, Berzigotti A. Diagnostic hepatic haemodynamic techniques: safety and radiation exposure. Liver Int 2017;37(1):148–154

Qi X, Berzigotti A, Cardenas A, Sarin SK. Emerging non-invasive approaches for diagnosis and monitoring of portal hypertension. Lancet Gastroenterol Hepatol 2018;3(10):708–719

Qi X, Li Z, Huang J, Zhu Y, Liu H, Zhou F, Liu C, Xiao C, Dong J, Zhao Y, Xu M, Xing S, Xu W, Yang C. Virtual portal pressure gradient from anatomic CT angiography. Gut 2015;64(6):1004–1005

Liu F, Ning Z, Liu Y, Liu D, Tian J, Luo H, An W, Huang Y, Zou J, Liu C, Liu C, Wang L, Liu Z, Qi R, Zuo C, Zhang Q, Wang J, Zhao D, Duan Y, Peng B, Qi X, Zhang Y, Yang Y, Hou J, Dong J, Li Z, Ding H, Zhang Y, Qi X. Development and validation of a radiomics signature for clinically significant portal hypertension in cirrhosis (CHESS1701): a prospective multicenter study. E BioMed 2018;36:151–158

Arora V, Maiwal R, Thomas SS, RajanV, Ali R, Kumar G, Jain P, Sarin SK. Albumin decreases the incidence of paracentesis induced circulatory dysfunction with less than 5 litres of ascitic tap in acute on chronic liver failure (ACLF) patients: randomized controlled trial (NCT02467348). J Hepatol 2018;68(1):S42–S43

Cabrera J, Falcón L, Gorriz E, et al. Abdominal decompression plays a major role in early postparacentesis haemodynamic changes in cirrhotic patients with tense ascites Gut 2001;48:384–389

Singh V, Singh A, Singh B, Vijayvergiya R, Sharma N, Ghai A, Bhalla A. Midodrine and clonidine in patients with cirrhosis and refractory or recurrent ascites: a randomized pilot study. Am J Gastroenterol 2013;108(4):560–567

Singh V, Kumar B, Nain CK, Singh B, Sharma N, Bhalla A, Sharma AK. Noradrenaline and albumin in paracentesis-induced circulatory dysfunction in cirrhosis: a randomized pilot study. J Intern Med 2006;260(1):62–68

Xue R, Duan Z, Liu H, Chen L, Yu H, Ren M, Zhu Y, Jin C, Han T, Gao Z, Meng Q. A novel dynamic model for predicting outcome in patients with hepatitis B virus related acute-on-chronic liver failure. Oncotarget 2017;8(65):108970–108980. https://doi.org/10.18632/oncotarget.22447

Song DS, Kim TY, Kim DJ, Korean Acute-on-Chronic Liver Failure (KACLiF) Study Group, et al. Validation of prognostic scores to predict short-term mortality in patients with acute-on-chronic liver failure. J Gastroenterol Hepatol 2017. https://doi.org/10.1111/jgh.13991 (Epub ahead of print)

Chan CA, Fan ST, Lo CM, Liu CL, Chan SC, Ng KK, et al. Liver transplantation for acute-on-chronic liver failure. Hepatol Int 2009;3:571–581

Mathurin P, et al. Corticosteroids improve short-term survival in patients with severe alcoholic hepatitis: meta-analysis of individual patient data. Gut 2011;60:255–260

Wong RJ, Aguilar M, Gish RG, Cheung R, Ahmed A. The impact of pretransplant hepatic encephalopathy on survival following liver transplantation. Liver Transpl 2015;21:873–880.

Yeoman AD, O’Grady JG, Heneghan MA. Prognosis of acute severe autoimmune hepatitis (AS-AIH): the role of corticosteroids in modifying outcome. J Hepatol 2014. https://doi.org/10.1016/j.jhep.2014.05.021 .

Nakao M, Nakayama N, Uchida Y, Tomiya T, Ido A, Sakaida I, Yokosuka O, Takikawa Y, Inoue K, Genda T, Shimizu M, Terai S, Tsubouchi H, Takikawa H, Mochida S. Nationwide survey for acute liver failure and late-onset hepatic failure in Japan. J Gastroenterol 2017. https://doi.org/10.1007/s00535-017-1394-2 (Epub ahead of print)

Yeoman AD, Westbrook RH, Portmann C, O’Grady OJ, Harrison PM, Heneghan MA. Early predictors of corticosteroid treatment failure in icteric presentations of autoimmune hepatitis. Hepatolog. 2011;53:926–934

Wang J, Ma K, Han M, Guo W, Huang J, Yang D, Zhao X, Song J, Tian D, Qi J, Huang Y, Ning Q. Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic liver failure: validation of the TPPM model. Hepatol Int 2014;8(1):64–71 (153n)

Ma K, Guo W, Han M, et al. Entecavir treatment prevents disease progression in hepatitis B virus-related acute-on-chronic liver failure: establishment of a novel logistical regression model. Hepatol Int 2012;6(4):735–743 (153n)

Tao C, Zhongyuan Y, Kumar A, Choudhury for APASL ACLF Research Consortium (AARC). Hepatology 2017; 67 ([ABSTRACT] Supple,ID#2776063.[155n])

Agrawal S, Duseja A, Gupta T, Dhiman RK, Chawla Y. Simple organ failure count versus CANONIC grading system for predicting mortality in acute-on-chronic liver failure. J Gastroenterol Hepatol 2015;30(3):575–581

Hoofnagle JH. Reactivation of hepatitis B. Hepatology 2009;49:S156–S165

Jindal A, Kumar M, Sarin SK. Management of acute hepatitis B and reactivation of hepatitis B. Liver Int 2013;33(Suppl 1):164–175

Sun LJ, Yu JW, Zhao YH, Kang P, Li SC. Influential factors of prognosis in lamivudine treatment for patients with acute-on-chronic hepatitis B liver failure. J Gastroenterol Hepatol 2010;25(3):583–590

Hwang JP, Lok AS. Management of patients with hepatitis B who require immunosuppressive therapy. Nat Rev Gastroenterol Hepatol 2013. https://doi.org/10.1038/nrgastro.2013.216

Kusumoto S, Tanaka Y, Mizokami M, Ueda R. Strategy for preventing hepatitis B reactivation in patients with resolved HBV infection following rituximab containing chemotherapy. Hepatology 2013. https://doi.org/10.1002/hep.26963

Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G, et al. Acute-on chronic liver failure. J Hepatol 2012;57(6):1336–1348

Bahirwani R, Shaked O, Bewtra M, Forde K, Reddy KR. Acute-on-chronic liver failure before liver transplantation: impact on post transplant outcomes. Transplantation 2011;92(8):952–957

Lin KH, Liu JW, Chen CL, Wang SH, Lin CC, Liu YW, et al. Impacts of pretransplant infections on clinical outcomes of patients with acute-on-chronic liver failure who received living donor liver transplantation. PLoS One 2013;8(9):e72893

Pamecha V, Kumar S, Bharathy KG. Liver transplantation in acute-on-chronic liver failure: challenges and an algorithm for patient selection and management. Hepatol Int. 2015.

Chan AC, Fan ST, Lo CM, Liu CL, Chan SC, Ng KK, et al. Liver transplantation for acute-on-chronic liver failure. Hepatol Int 2009;3(4):571–581

Chok KSh, Chan SC, Fung JY, Cheung TT, Chan AC, Fan ST, Lo CM. Survival outcomes of right-lobe living donor transplantation for patients with high model for end stage Liver Disease scores. Hepatobiliary Pancreat Dis Int 2013;12(3):256–262

Choudhury AK, Sharma M, Mehtab M, Sarin SK, for APASL ACLF Working party, et al. The decision for liver transplant in acute-on-chronic liver failure (ACLF)—first week is the crucial period-analysis of the APASL ACLF Research Consortium (AARC) prospective data of 1021 patients. J Hepatol 2016;64:S1–S51

Gustot T, Fernandez J, Garcia E, for CANONIC Study Investigators of the EASL-CLIF Consortium, et al. Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology 2015;62(1):243–252

Wong RJ, Aguilar M, Gish RG, Cheung R, Ahmed A. The impact of pretransplant hepatic encephalopathy on survival following liver transplantation. Liver Transpl 2015;21:873–880

Staufer K, Roedl K, Kivaranovic D, Drolz A, Horvatits T, Rasoul-Rockenschaub S, Zauner C, Trauner M, Fuhrmann V. Renal replacement therapy in critically ill liver cirrhotic patients-outcome and clinical implications. Liver Int 2017;37(6):843–850. https://doi.org/10.1111/liv.13389 (Epub 2017 Apr 5).

Cheng CH, Lee CF, Soong RS, Wu TH, Chan KM, Chou HS, Wu TJ, Yu MC, Lee WC. Risk factors and clinical outcomes of ventilator-associated pneumonia in patients on the liver transplant waiting list. Transpl Proc. 2012;44(3):762–4.

Moon DB, Lee SG, Kang WH, Song GW, Jung DH, Park GC, Cho HD, Jwa EK, Kim WJ, Ha TY, Kim HJ. Adult living donor liver transplantation for acute-on-chronic liver failure in high- model for end-stage liver disease score patients. Am J Transpl 2017;17(7):1833–1842 (PMID: 28097804-64)

Putignano A, Gustot T. New concepts in acute-on-chronic liver failure: implications for liver transplantation. Liver Transpl 2017;23(2):234–243. https://doi.org/10.1002/lt.24654 (Epub 2017 Jan 6. Review. PMID: 27750389-65)

Artru F, Louvet A, Ruiz I, et al. Liver transplantation in the most severely ill cirrhotic patients: a multicenter study in acute-on-chronic liver failure grade 3. J Hepatol 2017. https://doi.org/10.1016/j.jhep.2017.06.009 .

Reddy MS, Rajalingam R, Rela M. Liver transplantation in acute-on-chronic liver failure: lessons learnt from acute liver failure setting. Hepatol Int 2015;9(4):508–513. https://doi.org/10.1007/s12072-014-9603-z .

Sarin SK, Choudhury A. Management of acute-on-chronic liver failure: an algorithmic approach. Hepatol Int 2018;12(5):402–416. https://doi.org/10.1007/s12072-018-9887-5 .

Jalan R, Williams R. Acute-on-chronic liver failure: pathophysiological basis of therapeutic options. Blood Purif 2002;20:252–261

Hassanein TI, Tofteng F, Brown RS Jr, McGuire B, Lynch P, Mehta R, et al. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology 2007;46(6):1853–1862

Banares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 2013;57:1153–1162

Kribben A, Gerken G, Haag S, Herget-Rosenthal S, Treichel U, Betz C, et al. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 2012;142:782–789

Mitzner SR, Stange J, Klammt S, Risler T, Erley CM, Bader BD, et al. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl 2000;6:277–286

Catalina MV, Barrio J, Anaya F, Salcedo M, Rincón D, Clemente G, Bañares R. Hepatic and systemic haemodynamic changes after MARS in patients with acute on chronic liver failure. Liver Int 2003;23(Suppl 3):39–43

Laleman W, Wilmer A, Evenepoel P, Elst IV, Zeegers M, Zaman Z, et al. Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure. Crit Care 2006;10:R108

Guo LM, Liu JY, Xu DZ, Li BS, Han H, Wang LH, et al. Application of Molecular Adsorbents Recirculating System to remove NO and cytokines in severe liver failure patients with multiple organ dysfunction syndrome. Liver Int 2003;23(Suppl 3):16–20

Atienza Merino G. Evaluation of extracorporeal liver support systems in thetreatment of liver failure: a systematic review. Gastroenterol Hepatol 2010;33(5):352–362

Kjaergard LL, Liu J, Als-Nielsen B, Gluud C. Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review. JAMA 2003;289(2):217–222

Larsen FS, Schmidt LE, Bernsmeier C, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol 2016;64(1):69–78 (PMID: 26325537)

Ling Q, Xu X, Wei Q, Liu X, Guo H, Zhuang L, et al. Downgrading MELD improves the outcomes after liver transplantation in patients with acute-on-chronic hepatitis B liver failure. PLoS One 2012;7(1):e30322

Xu X, Liu X, Ling Q, Wei Q, Liu Z, Xu X, et al. Artificial liver support system combined with liver transplantation in treatment of patients with acute-on-chronic liver failure. PLoS One 2013;8(3):e58738

Duan XZ, Liu FF, Tong JJ, Yang HZ, Chen J, Liu XY, et al. Granulocyte colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acute-on-chronic liver failure. World J Gastroenterol 2013;19:1104–1110

Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: from liver transplantation to cell factory. J Hepatol 2015;62(1S):S157–S169

Liao X, AnCheng JY, Zhou QJ, Liao C. Therapeutic effect of autologous bone marrow-derived liver stem cells transplantation in hepatitis B virus-induced liver cirrhosis. Hepatogastroenterology 2013;60(123):406–409

Di Campli C, Zocco MA, Saulnier N, et al. Safety and efficacy profile of G-CSF therapy in patients with acute on chronic liver failure. Dig Liver Dis 2007;39:1071–1076

Singh V, Sharma AK, Sharma N, Sharma R. Granulocyte colony-stimulating factor in severe alcoholic hepatitis: a randomized pilot study. Am J Gastroenterol 2014;109:1417–1423

Kedarisetty CK, Anand L, Bhatia V, Sarin SK. Combination of granulocyte colony-stimulating factor and erythropoietin improves outcomes of patients with decompensated cirrhosis. Gastroenterology 2015;148(7):1362.e7–1370.e7

Meng F, Francis H, Glaser S, Alpini G. Role of stem cell factor and granulocyte colony-stimulating factor in remodeling during liver regeneration. Hepatology 2012;55(1):209–221

Pusic I, Di Persio JF. Update on clinical experience with amd3100, an sdf-1/cxcl12-cxcr4 inhibitor, in mobilization of hematopoietic stem and progenitor cells. Curr Opin Hematol 2010;17:319–326

Alam S, Lal BB, Sood V, Rawat D. Pediatric acute-on-chronic liver failure in a specialized liver unit: prevalence, profile, outcome and predictive factors. J Pediatr Gastroenterol Nutr 2016;63(4):400–405. https://doi.org/10.1097/MPG.0000000000001179

Lal J, Thapa BR, Rawal P, Ratho RK, Singh K. Predictors of outcome in acute-on-chronic liver failure in children. Hepatol Int 2011;5:693–697

Jagadisan B, Srivastava A, Yachha SK, Poddar U. Acute-on-chronic liver disease in children from the developing world: recognition and prognosis. J Pediatr Gastroenterol Nutr 2012;54:77–82

Lal BB, Sood V, Khanna R, Alam S. How to identify the need for liver transplantation in pediatric acute-on-chronic liver failure? Hepatol Int. 2018;12(6):552–9.

Squires RH Jr, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr 2006;148:652–658

Lal BB, Alam S, Sood V, Rawat D, Khanna R. Profile, risk factors and outcome of acute kidney injury in pediatric acute-on-chronic liver failure. Liver Int 2018;38(10):1777–1784. https://doi.org/10.1111/liv.13693