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

Shiv Kumar Sarin, Ashok Choudhury, Manoj K Sharma, Rakhi Maiwall, Mamun Al Mahtab, Salimur Rahman, Sanjiv Saigal, Neeraj Saraf, A S Soin, Harshad Devarbhavi, Dong Joon Kim, R K Dhiman, Ajay Duseja, Sunil Taneja, C E Eapen, Ashish Goel, Q Ning, Tao Chen, Ke Ma, Z Duan, Chen Yu, Sombat Treeprasertsuk, S S Hamid, Amna S Butt, Wasim Jafri, Akash Shukla, Vivek Saraswat, Soek Siam Tan, Ajit Sood, Vandana Midha, Omesh Goyal, Hasmik Ghazinyan, Anil Arora, Jinhua Hu, Manoj Sahu, P N Rao, Guan H Lee, Seng G Lim, Laurentius A Lesmana, Cosmas Rinaldi Lesmana, Samir Shah, V G Mohan Prasad, Diana A Payawal, Zaigham Abbas, A Kadir Dokmeci, Jose D Sollano, Gian Carpio, Ananta Shresta, G K Lau, Md Fazal Karim, Gamal Shiha, Rino Gani, Kemal Fariz Kalista, Man-Fung Yuen, Seema Alam, Rajeev Khanna, Vikrant Sood, Bikrant Bihari Lal, Viniyendra Pamecha, Ankur Jindal, V Rajan, Vinod Arora, Osamu Yokosuka, Madunil A Niriella, Hai Li, Xiaolong Qi, Atsushi Tanaka, Satoshi Mochida, Dominic Ray Chaudhuri, Ed Gane, Khin Maung Win, Wei Ting Chen, Mohd Rela, Dharmesh Kapoor, Amit Rastogi, Pratibha Kale, Archana Rastogi, Chhagan Bihari Sharma, Meenu Bajpai, Virender Singh, Madhumita Premkumar, Sudhir Maharashi, A Olithselvan, Cyriac Abby Philips, Anshu Srivastava, Surender K Yachha, Zeeshan Ahmad Wani, B R Thapa, Anoop Saraya, Shalimar, Ashish Kumar, Manav Wadhawan, Subash Gupta, Kaushal Madan, Puja Sakhuja, Vivek Vij, Barjesh C Sharma, Hitendra Garg, Vishal Garg, Chetan Kalal, Lovkesh Anand, Tanmay Vyas, Rajan P Mathur, Guresh Kumar, Priyanka Jain, Samba Siva Rao Pasupuleti, Yogesh K Chawla, Abhijit Chowdhury, Shahinul Alam, Do Seon Song, Jin Mo Yang, Eileen L Yoon, APASL ACLF Research Consortium (AARC) for APASL ACLF working Party., Shiv Kumar Sarin, Ashok Choudhury, Manoj K Sharma, Rakhi Maiwall, Mamun Al Mahtab, Salimur Rahman, Sanjiv Saigal, Neeraj Saraf, A S Soin, Harshad Devarbhavi, Dong Joon Kim, R K Dhiman, Ajay Duseja, Sunil Taneja, C E Eapen, Ashish Goel, Q Ning, Tao Chen, Ke Ma, Z Duan, Chen Yu, Sombat Treeprasertsuk, S S Hamid, Amna S Butt, Wasim Jafri, Akash Shukla, Vivek Saraswat, Soek Siam Tan, Ajit Sood, Vandana Midha, Omesh Goyal, Hasmik Ghazinyan, Anil Arora, Jinhua Hu, Manoj Sahu, P N Rao, Guan H Lee, Seng G Lim, Laurentius A Lesmana, Cosmas Rinaldi Lesmana, Samir Shah, V G Mohan Prasad, Diana A Payawal, Zaigham Abbas, A Kadir Dokmeci, Jose D Sollano, Gian Carpio, Ananta Shresta, G K Lau, Md Fazal Karim, Gamal Shiha, Rino Gani, Kemal Fariz Kalista, Man-Fung Yuen, Seema Alam, Rajeev Khanna, Vikrant Sood, Bikrant Bihari Lal, Viniyendra Pamecha, Ankur Jindal, V Rajan, Vinod Arora, Osamu Yokosuka, Madunil A Niriella, Hai Li, Xiaolong Qi, Atsushi Tanaka, Satoshi Mochida, Dominic Ray Chaudhuri, Ed Gane, Khin Maung Win, Wei Ting Chen, Mohd Rela, Dharmesh Kapoor, Amit Rastogi, Pratibha Kale, Archana Rastogi, Chhagan Bihari Sharma, Meenu Bajpai, Virender Singh, Madhumita Premkumar, Sudhir Maharashi, A Olithselvan, Cyriac Abby Philips, Anshu Srivastava, Surender K Yachha, Zeeshan Ahmad Wani, B R Thapa, Anoop Saraya, Shalimar, Ashish Kumar, Manav Wadhawan, Subash Gupta, Kaushal Madan, Puja Sakhuja, Vivek Vij, Barjesh C Sharma, Hitendra Garg, Vishal Garg, Chetan Kalal, Lovkesh Anand, Tanmay Vyas, Rajan P Mathur, Guresh Kumar, Priyanka Jain, Samba Siva Rao Pasupuleti, Yogesh K Chawla, Abhijit Chowdhury, Shahinul Alam, Do Seon Song, Jin Mo Yang, Eileen L Yoon, APASL ACLF Research Consortium (AARC) for APASL ACLF working Party.

Abstract

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

Keywords: AARC; ALF; Acute decompensation; Alcoholic liver disease; Chronic liver disease; Cirrhosis; Decompensation; Jaundice; Liver failure.

Conflict of interest statement

Shiv Kumar Sarin et al. declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Concept of ACLF and the cohorts included in different definitions. The figure describes the response of the liver to an acute hepatic injury, depending on the underlying hepatic injury, prior decompensation, time frame from insult to presentation with decompensation and reversibility with mitigation of the acute insult. The spectrum extends from acute liver failure, acute-on-chronic liver failure, acute decompensation, end-stage liver disease. ACLF is distinct like ALF when the APASL definition is considered. APASL definition is simple and homogenous and is distinct
Fig. 2
Fig. 2
Sequence of events in Diagnostic Criteria of ACLF: East vs. West. The figure clearly describes the sequence of organ failure and its mechanism. An acute hepatic insult leading to hepatic decompensation is the driver and subsequent extrahepatic organ failure is due to failure of recovery/regeneration and development of sepsis after a Golden Window. With consideration of sepsis as the intiating factor and development of extrahepatic organ involvement as a part of definition leads to late identification of the ACLF patients where the therapeutic windos is lost. The difference between ACLF, AD and ESLD (as in Fig. 1) is blurred and entity is heterogenous. So pure hepatic insult leading to hepatic failure at the beginning and subsequent extrahepatic organ failure as complication, not defining complex is the crux in managing this group of liver disease patient
Fig. 3
Fig. 3
Golden window in ACLF. ACLF is the state of acute inflammatory response with cytokine burst. The SIRS is a response to this inflammation and subsequent resolution of inflammation and recovery or persistence of inflammation (leading to Compensatory Anti-inflammatory Inflammatory Response Syndrome-CARS) and sepsis. Patients of ACLF in a period of 7 days develop SIRS (which can be infective or sterile) but both the things lead to complications and sepsis develops subsequently. This time period is the therapeutic Golden Window. SIRS needs consideration for organ support, antibiotics for occult sepsis and prioritization for definitive therapy, i.e., liver transplant
Fig. 4
Fig. 4
Algorithm for management of ACLF. The algorithmic approach to ACLF is highlighted based on the severity of liver failure, acute etiology and specific therapy and dynamic disease course. The specific treatment initiated, but if the disease severity is more, i.e., AARC Score (consideration of bilirubin, creatinine, INR, lactate and HE grade) 11 or more the response is poor with best medical supportive car; hence, early consideration for liver transplant should be done, whereas other group needs to be seen for 4–7 days with specific therapy and standard medical therapy. Any deterioration or AARC score 11 or more needs to consider LT. The presence of extrahepatic organ failure needs to be managed, and optimization and improvement need to be correlated with over all recovery else poor prognoses to be considered
Fig. 5
Fig. 5
Comparison of AARC score against other disease severity score

References

    1. 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. doi: 10.1007/s12072-014-9580-2.
    1. 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.
    1. Choudhury A., Jindal A., Maiwall R., Sharma M. K., Sharma B. C., Pamecha V., Mahtab M., Rahman S., Chawla Y. K., Taneja S., Tan S. S., Devarbhavi H., Duan Z., Yu Chen, Ning Q., Jia Ji Dong, Amarapurkar D., Eapen C. E., Goel A., Hamid S. S., Butt A. S., Jafri W., Kim D. J., Ghazinian H., Lee G. H., Sood Ajit, Lesmana L. A., Abbas Z., Shiha G., Payawal D. A., Dokmeci A. K., Sollano J. D., Carpio G., Lau G. K., Karim F., Rao P. N., Moreau R., Jain P., Bhatia P., Kumar G., Sarin S. K. Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models. Hepatology International. 2017;11(5):461–471. doi: 10.1007/s12072-017-9816-z.
    1. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490. doi: 10.1136/bmj.328.7454.1490.
    1. O’Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet. 1993;342:273–275. doi: 10.1016/0140-6736(93)91818-7.
    1. 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. doi: 10.1016/j.jhep.2014.11.012.
    1. Sen S, William R, Jalan R. The pathophysiological basis of acute-on- chronic liver failure. Liver. 2002;22(Suppl 2):5–13. doi: 10.1034/j.1600-0676.2002.00001.x.
    1. 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. doi: 10.1111/j.1478-3231.2012.02790.x.
    1. 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. doi: 10.1002/hep.30056.
    1. 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. doi: 10.1053/jhep.2002.31250.
    1. 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. doi: 10.1053/j.gastro.2013.02.042.
    1. 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. doi: 10.3892/mmr.2014.1973.
    1. 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. doi: 10.1111/1469-0691.12611.
    1. 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. doi: 10.1186/1743-422X-11-9.
    1. 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. doi: 10.1097/MCG.0b013e318282971e.
    1. 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. doi: 10.1136/gut.51.4.597.
    1. 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 doi: 10.1111/ajt.12649.
    1. 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 doi: 10.1002/hep.26963.
    1. 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. doi: 10.4254/wjh.v5.i11.612.
    1. Huang M, Huang L. Reactivation of hepatitis C viral infection after treatment with infliximab. J Clin Gastroenterol. 2014;48(2):189–190. doi: 10.1097/MCG.0000000000000001.
    1. 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. doi: 10.1016/j.cgh.2013.03.025.
    1. 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. doi: 10.1111/j.1478-3231.2008.01887.x.
    1. 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.
    1. 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. doi: 10.1111/j.1440-1746.2007.05243.x.
    1. 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. doi: 10.1016/j.jhep.2006.09.016.
    1. 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. 9. Philadelphia: WB Saunders; 2010. p. 1351.
    1. Moreau R, Arroyo V. Acute-on-chronic liver failure: a new clinical entity. Clin Gastroenterol Hepatol. 2014 doi: 10.1016/j.cgh.2014.02.027.
    1. 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. doi: 10.1016/j.dld.2011.08.029.
    1. 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. doi: 10.1016/j.jhep.2004.10.019.
    1. 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. doi: 10.1007/s10620-010-1377-0.
    1. 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. doi: 10.1016/j.amjmed.2015.10.029.
    1. 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. doi: 10.1053/j.gastro.2015.03.006.
    1. 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. doi: 10.1002/hep.22633.
    1. Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis—a practical guide. Aliment Pharmacol Ther. 2013;37:1132–1156. doi: 10.1111/apt.12324.
    1. 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. doi: 10.1111/j.1872-034X.2007.00072.x.
    1. 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. doi: 10.1016/j.cld.2013.09.015.
    1. 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. doi: 10.1097/QAD.0b013e32814e6b08.
    1. 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. doi: 10.1017/S0950268899003593.
    1. 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. doi: 10.1093/aje/kwu095.
    1. 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. doi: 10.1016/j.jcma.2015.12.006.
    1. 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. doi: 10.1186/s12879-016-1344-2.
    1. 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. doi: 10.1097/MCG.0000000000000538.
    1. 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. doi: 10.1002/hep.27795.
    1. 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. doi: 10.1111/jgh.13340.
    1. 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. doi: 10.1016/j.jhep.2014.05.021.
    1. 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. doi: 10.1002/hep.24080.
    1. 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 doi: 10.1002/hep.30205.
    1. 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. doi: 10.1053/j.gastro.2007.05.024.
    1. 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. doi: 10.1097/MCG.0b013e318254e9d4.
    1. Bruns T, Zimmermann HW, Stallmach A. Risk factors and outcome of bacterial infections in cirrhosis. World J Gastroenterol. 2014;20(10):2542–2554. doi: 10.3748/wjg.v20.i10.2542.
    1. Kim RD, Kim JS, Watanabe G, Mohuczy D, Behrns KE. Liver regeneration and the atrophy-hypertrophy complex. Semin Interv Radiol. 2008;25:92–103. doi: 10.1055/s-2008-1076679.
    1. 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. doi: 10.1016/S0168-8278(03)00323-4.
    1. Desmet VJ, Roskams T. Cirrhosis reversal: a duel between dogma and myth. J Hepatol. 2004;40:860–867. doi: 10.1016/j.jhep.2004.03.007.
    1. 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.
    1. 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. doi: 10.1016/j.jhep.2011.02.012.
    1. 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. doi: 10.1111/his.12070.
    1. 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. doi: 10.1002/1096-9896(2000)9999:9999<::AID-PATH700>;2-5.
    1. 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. doi: 10.1111/j.1440-1746.2011.06844.x.
    1. 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. doi: 10.1016/S1665-2681(19)31415-2.
    1. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30(6):1356–1362. doi: 10.1002/hep.510300604.
    1. Loomba R, Sanyal A. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10(11):686–690. doi: 10.1038/nrgastro.2013.171.
    1. 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. doi: 10.1586/egh.11.47.
    1. 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. doi: 10.1007/s00428-011-1115-9.
    1. 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. doi: 10.1016/j.jhep.2007.05.001.
    1. 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. doi: 10.1155/2010/153986.
    1. 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
    1. 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. doi: 10.1007/s12664-012-0295-9.
    1. Seto WK, Lai CL, Yuen MF. Acute-on-chronic liver failure in chronic hepatitis B. J Gastroenterol Hepatol. 2012;27(4):662–669. doi: 10.1111/j.1440-1746.2011.06971.x.
    1. 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. doi: 10.1053/j.gastro.2005.04.014.
    1. Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and natural history of nonalcoholic fatty liver disease. J Hepatol. 2004;40:578–584. doi: 10.1016/j.jhep.2004.02.013.
    1. 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. doi: 10.1002/hep.24491.
    1. 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. doi: 10.1111/j.1572-0241.1998.044_c.x.
    1. 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.
    1. 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. doi: 10.1002/hep.24418.
    1. 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
    1. 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
    1. 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. doi: 10.1111/jgh.13799.
    1. 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. doi: 10.1136/gut.2009.189639.
    1. Jalan R, Mookerjee RP. Acute-on-chronic liver failure: an early liver biopsy is essential? Gut. 2010;59(11):1455–1456. doi: 10.1136/gut.2010.214627.
    1. 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. doi: 10.4253/wjge.v3.i1.6.
    1. 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. doi: 10.1136/gut.2009.189639.
    1. 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. doi: 10.1007/s00428-014-1547-0.
    1. 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. doi: 10.1007/s00428-012-1291-2.
    1. 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. doi: 10.1053/j.gastro.2011.11.027.
    1. 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.
    1. 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. 6. Boston: Little Brown; 1964. p. 114.
    1. Jeppesen JB, Mortensen C, Bendtsen F, Møller S. Lactate metabolism in chronic liver disease. Scand J Clin Lab Invest. 2013;73(4):293–299. doi: 10.3109/00365513.2013.773591.
    1. 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. doi: 10.1016/j.transproceed.2013.12.067.
    1. 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. doi: 10.1016/j.jhep.2013.10.004.
    1. 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. doi: 10.1097/01.CCM.0000050454.01978.3B.
    1. 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. doi: 10.1111/liv.12520.
    1. 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. doi: 10.1053/j.gastro.2010.06.019.
    1. Hoque R, Farooq A, Mehal WZ. Sterile inflammation in the liver and pancreas. J Gastroenterol Hepatol. 2013;28:61–67. doi: 10.1111/jgh.12018.
    1. Chovatiya R, Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol Cell. 2014;54:281–288. doi: 10.1016/j.molcel.2014.03.030.
    1. 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. doi: 10.1002/hep.21920.
    1. 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. doi: 10.1186/cc11882.
    1. 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. doi: 10.1371/journal.pone.0053885.
    1. Hotchkiss RS, Monneret G, Payen D. Sepsis induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–874. doi: 10.1038/nri3552.
    1. 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. doi: 10.1007/s10620-010-1377-0.
    1. 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. doi: 10.1111/liv.12415.
    1. Kox WJ, Volk T, Kox SN, Volk HD. Immunomodulatory therapies in sepsis. Intensive Care Med. 2000;26(Suppl 1):S124–S128. doi: 10.1007/s001340051129.
    1. 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. doi: 10.1016/j.jhep.2004.10.019.
    1. 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. doi: 10.1016/S0168-8278(13)60206-8.
    1. Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361:1279–1290. doi: 10.1056/NEJMra0809139.
    1. 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. doi: 10.1053/j.gastro.2010.07.043.
    1. 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. doi: 10.1053/j.gastro.2007.10.055.
    1. 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. doi: 10.1007/s10620-008-0421-9.
    1. Cárdenas A, Ginès P. Acute-on-chronic liver failure: the kidneys. Curr Opin Crit Care. 2011;17(2):184–189. doi: 10.1097/MCC.0b013e328344b3da.
    1. 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 doi: 10.1111/liv.13443.
    1. 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.
    1. 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. doi: 10.3748/wjg.v19.i48.9432.
    1. 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. doi: 10.1016/j.transproceed.2013.02.127.
    1. 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. doi: 10.1007/s10620-015-3921-4.
    1. 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. doi: 10.1016/S0168-8278(17)31542-8.
    1. Gonwa TA, Wadei HM. The challenges of providing renal replacement therapy in decompensated liver cirrhosis. Blood Purif. 2012;33:144–148. doi: 10.1159/000334149.
    1. 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. doi: 10.1002/hep.29488.
    1. Donovan JP, Schafer DF, Shaw BW, Jr, Sorrell MF. Cerebral edema and increased intracranial pressure in chronic liver disease. Lancet. 1998;351:719–721. doi: 10.1016/S0140-6736(97)07373-X.
    1. 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. doi: 10.1016/j.jceh.2017.04.001.
    1. 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. doi: 10.1007/s40265-018-1024-1.
    1. 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. doi: 10.1016/j.jhep.2010.07.045.
    1. 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. doi: 10.1038/ajg.2009.293.
    1. 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
    1. 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. doi: 10.1053/j.gastro.2009.08.045.
    1. 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. doi: 10.1002/hep.21303.
    1. 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 doi: 10.1002/hep.30103.
    1. 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. doi: 10.1016/j.jcrc.2017.07.053.
    1. 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. doi: 10.1016/S0168-8278(02)00208-8.
    1. Noris M, Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies? Blood. 1999;94:2569–2574. doi: 10.1182/blood.V94.8.2569.420k13_2569_2574.
    1. 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 doi: 10.1111/liv.14034.
    1. 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 doi: 10.1002/hep.30103.
    1. 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
    1. 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. doi: 10.1056/NEJMoa023153.
    1. 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):1361–1367. doi: 10.1111/jgh.12191.
    1. 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
    1. 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.
    1. 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.
    1. 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. doi: 10.1111/liv.13215.
    1. 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. doi: 10.1016/S2468-1253(18)30232-2.
    1. 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. doi: 10.1136/gutjnl-2014-308543.
    1. 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.
    1. Arora V., Maiwall R., Thomas S.S., Rajan V., Ali R., Kumar G., Jain P., Sarin S.K. 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) Journal of Hepatology. 2018;68:S42–S43. doi: 10.1016/S0168-8278(18)30303-9.
    1. 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.
    1. 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. doi: 10.1038/ajg.2013.9.
    1. 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. doi: 10.1111/j.1365-2796.2006.01654.x.
    1. 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. doi: 10.18632/oncotarget.22447.
    1. 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 doi: 10.1111/jgh.13991.
    1. 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. doi: 10.1007/s12072-009-9148-8.
    1. 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. doi: 10.1136/gut.2010.224097.
    1. Wong Robert J., Aguilar Maria, Gish Robert G., Cheung Ramsey, Ahmed Aijaz. The impact of pretransplant hepatic encephalopathy on survival following liver transplantation. Liver Transplantation. 2015;21(7):873–880. doi: 10.1002/lt.24153.
    1. 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 doi: 10.1016/j.jhep.2014.05.021.
    1. 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 doi: 10.1007/s00535-017-1394-2.
    1. 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. Hepatology. 2011;53:926–934. doi: 10.1002/hep.24141.
    1. 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. doi: 10.1007/s12072-013-9485-5.
    1. 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. doi: 10.1007/s12072-012-9344-9.
    1. Tao C, Zhongyuan Y, Kumar A, Choudhury for APASL ACLF Research Consortium (AARC). Hepatology 2017; 67 ([ABSTRACT] Supple,ID#2776063.[155n])
    1. 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. doi: 10.1111/jgh.12778.
    1. Hoofnagle JH. Reactivation of hepatitis B. Hepatology. 2009;49:S156–S165. doi: 10.1002/hep.22945.
    1. Jindal A, Kumar M, Sarin SK. Management of acute hepatitis B and reactivation of hepatitis B. Liver Int. 2013;33(Suppl 1):164–175. doi: 10.1111/liv.12081.
    1. 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. doi: 10.1111/j.1440-1746.2009.06089.x.
    1. Hwang JP, Lok AS. Management of patients with hepatitis B who require immunosuppressive therapy. Nat Rev Gastroenterol Hepatol. 2013 doi: 10.1038/nrgastro.2013.216.
    1. 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 doi: 10.1002/hep.26963.
    1. 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. doi: 10.1016/j.jhep.2012.06.026.
    1. 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. doi: 10.1097/TP.0b013e31822e6eda.
    1. 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. doi: 10.1371/journal.pone.0072893.
    1. 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.
    1. 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. doi: 10.1007/s12072-009-9148-8.
    1. 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. doi: 10.1016/S1499-3872(13)60042-9.
    1. 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. doi: 10.1016/j.jhep.2016.01.006.
    1. 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. doi: 10.1002/hep.27849.
    1. 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. doi: 10.1002/lt.24153.
    1. 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. doi: 10.1111/liv.13389.
    1. 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):762–764. doi: 10.1016/j.transproceed.2012.03.030.
    1. 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 Transplant. 2017;17(7):1833–1842. doi: 10.1111/ajt.14198.
    1. Putignano A, Gustot T. New concepts in acute-on-chronic liver failure: implications for liver transplantation. Liver Transpl. 2017;23(2):234–243. doi: 10.1002/lt.24654.
    1. 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 doi: 10.1016/j.jhep.2017.06.009.
    1. 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. doi: 10.1007/s12072-014-9603-z.
    1. Sarin SK, Choudhury A. Management of acute-on-chronic liver failure: an algorithmic approach. Hepatol Int. 2018;12(5):402–416. doi: 10.1007/s12072-018-9887-5.
    1. Jalan R, Williams R. Acute-on-chronic liver failure: pathophysiological basis of therapeutic options. Blood Purif. 2002;20:252–261. doi: 10.1159/000047017.
    1. 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. doi: 10.1002/hep.21930.
    1. 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. doi: 10.1002/hep.26185.
    1. 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. doi: 10.1053/j.gastro.2011.12.056.
    1. 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. doi: 10.1053/lv.2000.6355.
    1. 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. doi: 10.1034/j.1478-3231.23.s.3.10.x.
    1. 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. doi: 10.1186/cc4985.
    1. 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. doi: 10.1034/j.1478-3231.23.s.3.7.x.
    1. Atienza Merino G. Evaluation of extracorporeal liver support systems in thetreatment of liver failure: a systematic review. Gastroenterol Hepatol. 2010;33(5):352–362. doi: 10.1016/j.gastrohep.2010.01.002.
    1. 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. doi: 10.1001/jama.289.2.217.
    1. 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. doi: 10.1016/j.jhep.2015.08.018.
    1. 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. doi: 10.1371/journal.pone.0030322.
    1. 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. doi: 10.1371/journal.pone.0058738.
    1. 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. doi: 10.3748/wjg.v19.i7.1104.
    1. Forbes SJ, Gupta S, Dhawan A. Cell therapy for liver disease: from liver transplantation to cell factory. J Hepatol. 2015;62(1S):S157–S169. doi: 10.1016/j.jhep.2015.02.040.
    1. 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.
    1. 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. doi: 10.1016/j.dld.2007.08.006.
    1. 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. doi: 10.1038/ajg.2014.154.
    1. 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. doi: 10.1053/j.gastro.2015.02.054.
    1. 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. doi: 10.1002/hep.24673.
    1. 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. doi: 10.1097/MOH.0b013e328338b7d5.
    1. 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. doi: 10.1097/MPG.0000000000001179.
    1. 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. doi: 10.1007/s12072-010-9217-z.
    1. 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. doi: 10.1097/MPG.0b013e318228d7da.
    1. 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):552–559. doi: 10.1007/s12072-018-9901-y.
    1. 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. doi: 10.1016/j.jpeds.2005.12.051.
    1. 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. doi: 10.1111/liv.13693.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe