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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2016, Vol. 10 Issue (1) : 1-17     DOI: 10.1007/s11684-016-0439-x
Overview on acute-on-chronic liver failure
Jing Zhang1,3,Shan Gao2,3,Zhongping Duan2,3,*(),Ke-Qin Hu4,*()
1. Department of Hepatitis C and Drug Induced Liver Injury, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
2. Beijing Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
3. Collaborative Innovation Center of Infectious Diseases, Beijing 100069, China
4. Division of Gastroenterology and Hepatology, University of California, Irvine, Medical Center, Orange, CA 92868, USA
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Liver failure (LF) is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. Clinical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF (ACLF), and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.

Keywords liver failure      chronic liver failure      acute-on-chronic liver failure      diagnosis      prognosis      treatment     
Corresponding Authors: Zhongping Duan,Ke-Qin Hu   
Just Accepted Date: 25 February 2016   Online First Date: 16 March 2016    Issue Date: 31 March 2016
URL:     OR
Acute LF Acute-on-chronic LF Chronic LF
Epidemiology Uncommon Common Most common
Underlying liver disease None Yes Yes
Etiology Various liver injury inducing factors Intrahepatic or extrahepatic factors CLD with slow progression
Precipitating factors None Yes (some unknown) None
Time <26 weeks <26 weeks >26 weeks
Duration Days Weeks Months to years
Essential condition of diagnosis Hepatic encephalopathy (HE), INR INR, TBIL, and ascites/HE (APASL) No specific criteria (China, the only ?factor is PTA<40%)
Pathology Extensive necrosis Liver fibrosis in various degrees, ?acute hepatocyte injury, and necrosis Diffuse hepatic fibrosis and forma-?tion of pseudo-lobules accompa-?nied with distributed hepatocyte ?necrosis
Clinical presentation HE, brain edema, coagulation defects Coagulation defects, hemodynamic ?dysfunction, immune function failure, ?SIRS, and multiple organ failure Multiple organ failure, and SIRS
Therapy Liver transplantation Spontaneous recovery, transplantation Liver transplantation
Prognostic indices King’s college score Liver specific model (CTP and MELD), ?general model (SAPS II and APACHE), ?and organ failure model (OSF, SOFA, ?and CLIF-SOFA) MELD
Fatality rate High Higher than cirrhosis with same MELD ?score
Tab.1  Clinical presentation and diagnostic criteria of three different types of liver failure (LF)
Definition Acute (usually within four weeks) liver ?decompensation in patients with CLDs Acute hepatic insult manifesting as ?jaundice and coagulopathy, complicated ?within four weeks by ascites and/or ?encephalopathy in a patient with pre-?viously diagnosed or undiagnosed CLD Acute deterioration of pre-existing CLD, ?usually related to a precipitating event and ?associated with increased mortality at three ?months due to multi-system organ failure
Diagnostic criteria 1. Progressively deepening jaundice ?(TBil ?≥10?mg/dl or daily increase ??≥1?mg/dl)2. PTA≤40% or INR?≥1.53. with or without HE or other ?complications4. divided into 3 grades 1. Previously diagnosed or undiagnosed ?CLD2.TBil>?5?mg/dl and INR>1.5 or PTA??<?40%3.Ascites and/or encephalopathy in four ?weeks4. No grades ACLF-1: renal failure or a non-renal organ ?failure associated with creatinine 1.5–2 ?mg/dl and/or grades I–II encephalopathy?ACLF-2: two organ failures?ACLF-3: three or more organ failures
Predisposition Compensated liver disease Compensated liver disease Stable compensated or decompensated ?cirrhosis to date
Precipitating factors Not mentioned Infectious and noninfectious causes direct ?hepatic insult Infectious and noninfectious causes direct ?hepatic insult or not (especially infection)
Tab.2  Comparison of ACLF diagnostic criteria by CMA, APASL, and EASL-AASLD
Fig.1  Pathogenesis for different types of acute-on-chronic liver failure (ACLF) (Adopted from reference [24] with permission from Elsevier). Three types of ACLF are suggested. Type A ACLF is non-cirrhotic ACLF, type B is cirrhotic ACLF, and type C is cirrhotic ACLF with previous hepatic decompensation.
1 Sarin SK, Kumar A, Almeida JA, Chawla YK, Fan ST, Garg H, de Silva HJ, Hamid SS, Jalan R, Komolmit P, Lau GK, Liu Q, Madan K, Mohamed R, Ning Q, Rahman S, Rastogi A, Riordan SM, Sakhuja P, Samuel D, Shah S, Sharma BC, Sharma P, Takikawa Y, Thapa BR, Wai CT, Yuen MF. Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009; 3(1): 269–282
doi: 10.1007/s12072-008-9106-x pmid: 19669378
2 Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, Gustot T, Saliba F, Domenicali M, Gerbes A, Wendon J, Alessandria C, Laleman W, Zeuzem S, Trebicka J, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL–CLIF Consortium.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144(7): 1426–1437, 1437.e1–1437.e9
doi: 10.1053/j.gastro.2013.02.042 pmid: 23474284
3 Polson J, Lee WM; American Association for the Study of Liver Disease. AASLD position paper: the management of acute liver failure. Hepatology 2005; 41(5): 1179–1197
doi: 10.1002/hep.20703 pmid: 15841455
4 Francesco VU, Giacomo L, Fabio M, Fabio M. Acute on chronic liver failure: from pathophysiology to clinical management. Trends Anaesth Crit Care 2013; 3(3): 122–129
doi: 10.1016/j.tacc.2013.01.006
5 Bruno S, Saibeni S, Bagnardi V, Vandelli C, De Luca M, Felder M, Fracanzani AL, Prisco C, Vitaliani G, Simone L, Gaeta GB, Stanzione M, Persico M, Furlan C, Stroffolini T, Salerno F, Maisonneuve P, Almasio PL; AISF (Italian Association for the Study of the Liver) – EPA-SCO Collaborative Study Group. Mortality risk according to different clinical characteristics of first episode of liver decompensation in cirrhotic patients: a nationwide, prospective, 3-year follow-up study in Italy. Am J Gastroenterol 2013; 108(7): 1112–1122
doi: 10.1038/ajg.2013.110 pmid: 23732467
6 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 pmid: 23186071
7 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 pmid: 21978580
8 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 pmid: 20675694
9 Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. 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 pmid: 22429562
10 Bajaj JS, O’Leary JG, Reddy KR, Wong F, Biggins SW, Patton H, Fallon MB, Garcia-Tsao G, Maliakkal B, Malik R, Subramanian RM, Thacker LR, Kamath PS; North American Consortium For The Study Of End-Stage Liver Disease Nacseld. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology 2014; 60(1): 250–256
doi: 10.1002/hep.27077 pmid: 24677131
11 Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Diagnostic and treatment guidelines for liver failure. Chin J Hepatol (Zhonghua Gan Zang Bing Za Zhi) 2006; 14(9): 643–646 (in Chinese)
pmid: 16995974
12 Amarapurkar DN, Dharod MV, Chandnani MR, Baijal R, Kumar P, Patel N, Kamani P, Shah N, Jain M, Gupta DT, Issar S, Gautam S, Kulkarni SS, Shah A, Doshi SS. Prospective multicentric study on acute on chronic liver failure by apasl vs easl-aasld criteria. Hepatology 2013; 58(4 Suppl): 94A
13 Liu X, Lin W, Wei XH, Ma LX, Jin CG, Wu WF, Zhang J, Duan ZP. The acute-on-chronic liver failure diagnosis criteria of EASL is not consistent to that of APASAL. Hepatology 2013; 58(4 Suppl): 94A
14 Zhang Q, Li Y, Han T, Nie C, Cai J, Liu H, Liu Y. Comparison of current diagnostic criteria for acute-on-chronic liver failure. PLoS ONE 2015; 10(3): e0122158
doi: 10.1371/journal.pone.0122158 pmid: 25785855
15 Olson JC, Kamath PS. Acute-on-chronic liver failure: what are the implications? Curr Gastroenterol Rep 2012; 14(1): 63–66
doi: 10.1007/s11894-011-0228-2 pmid: 22086408
16 Duseja A, Chawla YK, Dhiman RK, Kumar A, Choudhary N, Taneja S. Non-hepatic insults are common acute precipitants in patients with acute on chronic liver failure (ACLF). Dig Dis Sci 2010; 55(11): 3188–3192
doi: 10.1007/s10620-010-1377-0 pmid: 20721624
17 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 pmid: 23526372
18 Rastogi A, Kumar A, Sakhuja P, Bihari C, Gondal R, Hissar S, Garg H, Sarin SK. 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 pmid: 21744153
19 Shi Y, Yang Y, Hu Y, Wu W, Yang Q, Zheng M, Zhang S, Xu Z, Wu Y, Yan H, Chen Z. Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults. Hepatology 2015; 62(1): 232–242
doi: 10.1002/hep.27795 pmid: 25800029
20 Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G, Arroyo V, Kamath PS. Acute-on chronic liver failure. J Hepatol 2012; 57(6): 1336–1348
doi: 10.1016/j.jhep.2012.06.026 pmid: 22750750
21 Lai J, Yan Y, Mai L, Zheng YB, Gan WQ, Ke WM. Short-term entecavir versus lamivudine therapy for HBeAg-negative patients with acute-on-chronic hepatitis B liver failure. Hepatobiliary Pancreat Dis Int 2013; 12(2): 154–159
doi: 10.1016/S1499-3872(13)60025-9 pmid: 23558069
22 Cui YL, Yan F, Wang YB, Song XQ, Liu L, Lei XZ, Zheng MH, Tang H, Feng P. Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure. Dig Dis Sci 2010; 55(8): 2373–2380
doi: 10.1007/s10620-010-1257-7 pmid: 20512414
23 Jalan R, Yurdaydin C, Bajaj JS, Acharya SK, Arroyo V, Lin HC, Gines P, Kim WR, Kamath PS; World Gastroenterology Organization Working Party. Toward an improved definition of acute-on-chronic liver failure. Gastroenterology 2014; 147(1): 4–10
doi: 10.1053/j.gastro.2014.05.005 pmid: 24853409
24 Shi Y, Zheng MH, Yang Y, Wei W, Yang Q, Hu A, Hu Y, Wu Y, Yan H. Increased delayed mortality in patients with acute-on-chronic liver failure who have prior decompensation. J Gastroenterol Hepatol 2015; 30(4): 712–718
doi: 10.1111/jgh.12787 pmid: 25250673
25 Mookerjee RP, Lackner C, Stauber R, Stadlbauer V, Deheragoda M, Aigelsreiter A, Jalan R. The role of liver biopsy in the diagnosis and prognosis of patients with acute deterioration of alcoholic cirrhosis. J Hepatol 2011; 55(5): 1103–1111
doi: 10.1016/j.jhep.2011.02.021 pmid: 21376092
26 Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology 2000; 32(4 Pt 1): 734–739
doi: 10.1053/jhep.2000.17687 pmid: 11003617
27 Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R. Severe sepsis in cirrhosis. Hepatology 2009; 50(6): 2022–2033
doi: 10.1002/hep.23264 pmid: 19885876
28 Jalan R, Fernandez J, Wiest R, Schnabl B, Moreau R, Angeli P, Stadlbauer V, Gustot T, Bernardi M, Canton R, Albillos A, Lammert F, Wilmer A, Mookerjee R, Vila J, Garcia-Martinez R, Wendon J, Such J, Cordoba J, Sanyal A, Garcia-Tsao G, Arroyo V, Burroughs A, Ginès P. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol 2014; 60(6): 1310–1324
doi: 10.1016/j.jhep.2014.01.024 pmid: 24530646
29 Mookerjee RP, Stadlbauer V, Lidder S, Wright GA, Hodges SJ, Davies NA, Jalan R. Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome. Hepatology 2007; 46(3): 831–840
doi: 10.1002/hep.21737 pmid: 17680644
30 Wasmuth HE, Kunz D, Yagmur E, Timmer-Stranghöner A, Vidacek D, Siewert E, Bach J, Geier A, Purucker EA, Gressner AM, Matern S, Lammert F. 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 pmid: 15664244
31 Moreau R. Role of Infections in Acute-on-Chronic Liver Failure. Dig Dis 2015; 33(4): 577–581
doi: 10.1159/000375356 pmid: 26159276
32 Ambrosino G, Naso A, Feltracco P, Carraro P, Basso SM, Varotto S, Cillo U, Zanus G, Boccagni P, Brolese A, Plebani M, Giron G, D’Amico DF. Cytokines and liver failure: modification of TNF- and IL-6 in patients with acute on chronic liver decompensation treated with Molecular Adsorbent Recycling System (MARS). Acta Biomed 2003; 74(Suppl 2): 7–9
pmid: 15055025
33 Karvellas CJ, Pink F, McPhail M, Austin M, Auzinger G, Bernal W, Sizer E, Kutsogiannis DJ, Eltringham I, Wendon JA. Bacteremia, acute physiology and chronic health evaluation II and modified end stage liver disease are independent predictors of mortality in critically ill nontransplanted patients with acute on chronic liver failure. Crit Care Med 2010; 38(1): 121–126
doi: 10.1097/CCM.0b013e3181b42a1c pmid: 19770744
34 Wright G, Sharifi Y, Jover-Cobos M, Jalan R. The brain in acute on chronic liver failure. Metab Brain Dis 2014; 29(4): 965–973
doi: 10.1007/s11011-014-9553-0 pmid: 24838253
35 Thabut D, Massard J, Gangloff A, Carbonell N, Francoz C, Nguyen-Khac E, Duhamel C, Lebrec D, Poynard T, Moreau R. 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(6): 1872–1882
doi: 10.1002/hep.21920 pmid: 17972337
36 Helmy A, Jalan R, Newby DE, Hayes PC, Webb DJ. Role of angiotensin II in regulation of basal and sympathetically stimulated vascular tone in early and advanced cirrhosis. Gastroenterology 2000; 118(3): 565–572
doi: 10.1016/S0016-5085(00)70263-0 pmid: 10702208
37 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 pmid: 18688717
38 Garg H, Kumar A, Garg V, Kumar M, Kumar R, Sharma BC, Sarin SK. 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 pmid: 23488990
39 Mehta G, Mookerjee RP, Sharma V, Jalan R. Systemic inflammation is associated with increased intrahepatic resistance and mortality in alcohol-related acute-on-chronic liver failure. Liver Int 2015; 35(3): 724–734
doi: 10.1111/liv.12559 pmid: 24703488
40 Rincon D, Lo Iacono O, Ripoll C, Gomez-Camarero J, Salcedo M, Catalina MV, Hernando A, Clemente G, Matilla A, Nuñez O, Bañares R. Prognostic value of hepatic venous pressure gradient for in-hospital mortality of patients with severe acute alcoholic hepatitis. Aliment Pharmacol Ther 2007; 25(7): 841–848
doi: 10.1111/j.1365-2036.2007.03258.x pmid: 17373923
41 Romero-Gómez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol 2015; 62(2): 437–447
doi: 10.1016/j.jhep.2014.09.005 pmid: 25218789
42 Radha Krishna Y, Saraswat VA, Das K, Himanshu G, Yachha SK, Aggarwal R, Choudhuri 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 pmid: 19267864
43 Wlodzimirow KA, Eslami S, Chamuleau RA, Nieuwoudt M, Abu-Hanna A. Prediction of poor outcome in patients with acute liver failure-systematic review of prediction models. PLoS ONE 2012; 7(12): e50952
doi: 10.1371/journal.pone.0050952 pmid: 23272081
44 Joshi D, O’Grady J, Patel A, Shawcross D, Connor S, Deasy N, Willars C, Bernal W, Wendon J, Auzinger G. Cerebral oedema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy. Liver Int 2014; 34(3): 362–366
doi: 10.1111/liv.12257 pmid: 23844567
45 García-Martínez R, Córdoba J. Acute-on-chronic liver failure: the brain. Curr Opin Crit Care 2011; 17(2): 177–183
doi: 10.1097/MCC.0b013e328344b37e pmid: 21346567
46 Chen F, Ohashi N, Li W, Eckman C, Nguyen JH. Disruptions of occludin and claudin-5 in brain endothelial cells in vitro and in brains of mice with acute liver failure. Hepatology 2009; 50(6): 1914–1923
doi: 10.1002/hep.23203 pmid: 19821483
47 Rodrigo R, Cauli O, Gomez-Pinedo U, Agusti A, Hernandez-Rabaza V, Garcia-Verdugo JM, Felipo V. Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology 2010; 139(2): 675–684
doi: 10.1053/j.gastro.2010.03.040 pmid: 20303348
48 Wai CT. Correcting thrombocytopenia in patients with liver diseases: a difficult hurdle. J Gastroenterol Hepatol 2013; 28(2): 207–208
doi: 10.1111/jgh.12052 pmid: 23339384
49 Lin W, Jin CG, Liu XH, He JQ, Li M , Zhang SQ, Zhang YX, Chen H, Zhang CQ, Ma LX , Wei XH, Guo HQ, Li Z, Wu WF, Hu JH, Meng QH, Ding HG, Chen Y, Zheng SJ, Liu S, Zhang J, Duan ZP. A dynamic model for predicting outcome in patients with HBV related acute-on-chronic liver failure. Hepatology 2013; 58(4 Suppl): 93A
50 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 pmid: 21311322
51 Tsai MH, Peng YS, Chen YC, Liu NJ, Ho YP, Fang JT, Lien JM, Yang C, Chen PC, Wu CS. Adrenal insufficiency in patients with cirrhosis, severe sepsis and septic shock. Hepatology 2006; 43(4): 673–681
doi: 10.1002/hep.21101 pmid: 16557538
52 Fernández J, Escorsell A, Zabalza M, Felipe V, Navasa M, Mas A, Lacy AM, Ginès P, Arroyo V. Adrenal insufficiency in patients with cirrhosis and septic shock: effect of treatment with hydrocortisone on survival. Hepatology 2006; 44(5): 1288–1295
doi: 10.1002/hep.21352 pmid: 17058239
53 Martín-Llahí M, Guevara M, Torre A, Fagundes C, Restuccia T, Gilabert R, Solá E, Pereira G, Marinelli M, Pavesi M, Fernández J, Rodés J, Arroyo V, Ginès P. Prognostic importance of the cause of renal failure in patients with cirrhosis. Gastroenterology 2011; 140(2): 488–496.e4
doi: 10.1053/j.gastro.2010.07.043 pmid: 20682324
54 Wong F, Nadim MK, Kellum JA, Salerno F, Bellomo R, Gerbes A, Angeli P, Moreau R, Davenport A, Jalan R, Ronco C, Genyk Y, Arroyo V. Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis. Gut 2011; 60(5): 702–709
doi: 10.1136/gut.2010.236133 pmid: 21325171
55 Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11(2): R31
doi: 10.1186/cc5713 pmid: 17331245
56 Wong F, O’Leary JG, Reddy KR, Patton H, Kamath PS, Fallon MB, Garcia-Tsao G, Subramanian RM, Malik R, Maliakkal B, Thacker LR, Bajaj JS; North American Consortium for Study of End-Stage Liver Disease. New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection. Gastroenterology 2013; 145(6): 1280–8.e1
doi: 10.1053/j.gastro.2013.08.051 pmid: 23999172
57 Jenq CC, Tsai MH, Tian YC, Lin CY, Yang C, Liu NJ, Lien JM, Chen YC, Fang JT, Chen PC, Yang CW. RIFLE classification can predict short-term prognosis in critically ill cirrhotic patients. Intensive Care Med 2007; 33(11): 1921–1930
doi: 10.1007/s00134-007-0760-6 pmid: 17605129
58 Cholongitas E, Calvaruso V, Senzolo M, Patch D, Shaw S, O’Beirne J, Burroughs AK. RIFLE classification as predictive factor of mortality in patients with cirrhosis admitted to intensive care unit. J Gastroenterol Hepatol 2009; 24(10): 1639–1647
doi: 10.1111/j.1440-1746.2009.05908.x pmid: 19788604
59 Tsien CD, Rabie R, Wong F. Acute kidney injury in decompensated cirrhosis. Gut 2013; 62(1): 131–137
doi: 10.1136/gutjnl-2011-301255 pmid: 22637695
60 Bird GL. Investigation of alcoholic liver disease. Baillieres Clin Gastroenterol 1993; 7(3): 663–682
doi: 10.1016/0950-3528(93)90007-F pmid: 8219405
61 Weng HL, Cai X, Yuan X, Liebe R, Dooley S, Li H, Wang TL. Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure. Front Physiol 2015; 6: 178–182
doi: 10.3389/fphys.2015.00178 pmid: 26136687
62 Li H, Xia Q, Zeng B, Li ST, Liu H, Li Q, Li J, Yang SY, Dong XJ, Gao T, Munker S, Liu Y, Liebe R, Xue F, Li QG, Chen XS, Liu Q, Zeng H, Wang JY, Xie Q, Meng QH, Wang JF, Mertens PR, Lammert F, Singer MV, Dooley S, Ebert MP, Qiu DK, Wang TL, Weng HL. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol 2015; 63(1): 50–59
doi: 10.1016/j.jhep.2015.01.029 pmid: 25646889
63 Orrego H, Blake JE, Blendis LM, Medline A. Prognosis of alcoholic cirrhosis in the presence and absence of alcoholic hepatitis. Gastroenterology 1987; 92(1): 208–214
pmid: 3781189
64 Sakhuja P, Rastogi A, Gondal R, Garg H, Sarin SK. Acute on chronic liver failure—analysis of two distinct liver histological patterns. J Hepato 2008; 48: S95
doi: 10.1016/S0168-8278(08)60233-0
65 Bauer M, Press AT, Trauner M. The liver in sepsis: patterns of response and injury. Curr Opin Crit Care 2013; 19(2): 123–127
doi: 10.1097/MCC.0b013e32835eba6d pmid: 23448974
66 Santoni-Rugiu E, Jelnes P, Thorgeirsson SS, Bisgaard HC. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion. APMIS 2005; 113(11-12): 876–902
doi: 10.1111/j.1600-0463.2005.apm_386.x pmid: 16480456
67 Katoonizadeh A, Nevens F, Verslype C, Pirenne J, Roskams T. Liver regeneration in acute severe liver impairment: a clinicopathological correlation study. Liver Int 2006; 26(10): 1225–1233
doi: 10.1111/j.1478-3231.2006.01377.x pmid: 17105588
68 Galbois A, Das V, Carbonell N, Guidet B. Prognostic scores for cirrhotic patients admitted to an intensive care unit: which consequences for liver transplantation? Clin Res Hepatol Gastroenterol 2013; 37(5): 455–466
doi: 10.1016/j.clinre.2013.05.001 pmid: 23773487
69 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 pmid: 25251968
70 Lee M, Lee JH, Oh S, Jang Y, Lee W, Lee HJ, Yoo JJ, Choi WM, Cho YY, Cho Y, Lee DH, Lee YB, Yu SJ, Yi NJ, Lee KW, Kim YJ, Yoon JH, Suh KS, Lee HS. CLIF-SOFA scoring system accurately predicts short-term mortality in acutely decompensated patients with alcoholic cirrhosis: a retrospective analysis. Liver Int 2015; 35(1): 46–57
doi: 10.1111/liv.12683 pmid: 25203221
71 Levesque E, Saliba F, Ichaï P, Samuel D. Outcome of patients with cirrhosis requiring mechanical ventilation in ICU. J Hepatol 2014; 60(3): 570–578
doi: 10.1016/j.jhep.2013.11.012 pmid: 24280294
72 McPhail MJ, Shawcross DL, Abeles RD, Chang A, Patel V, Lee GH, Abdulla M, Sizer E, Willars C, Auzinger G, Bernal W, Wendon JA. Increased survival for patients with cirrhosis and organ failure in liver intensive care and validation of the Chronic Liver Failure-Sequential Organ Failure Scoring System. Clin Gastroenterol Hepatol 2015; 13(7): 1353–1360.e8
doi: 10.1016/j.cgh.2014.08.041 pmid: 25240417
73 Pan HC, Jenq CC, Lee WC, Tsai MH, Fan PC, Chang CH, Chang MY, Tian YC, Hung CC, Fang JT, Yang CW, Chen YC. Scoring systems for predicting mortality after liver transplantation. PLoS ONE 2014; 9(9): e107138
doi: 10.1371/journal.pone.0107138 pmid: 25216239
74 Pan HC, Jenq CC, Tsai MH, Fan PC, Chang CH, Chang MY, Tian YC, Hung CC, Fang JT, Yang CW, Chen YC. Scoring systems for 6-month mortality in critically ill cirrhotic patients: a prospective analysis of chronic liver failure-sequential organ failure assessment score (CLIF-SOFA). Aliment Pharmacol Ther 2014; 40(9): 1056–1065
doi: 10.1111/apt.12953 pmid: 25208465
75 Silva PE, Fayad L, Lazzarotto C, Ronsoni MF, Bazzo ML, Colombo BS, Dantas-Correa EB, Narciso-Schiavon JL, Schiavon LL. Single-centre validation of the EASL-CLIF consortium definition of acute-on-chronic liver failure and CLIF-SOFA for prediction of mortality in cirrhosis. Liver Int 2015; 35(5): 1516–1523
doi: 10.1111/liv.12597 pmid: 24840673
76 Theocharidou E, Pieri G, Mohammad AO, Cheung M, Cholongitas E, Agarwal B, Burroughs AK. The Royal Free Hospital score: a calibrated prognostic model for patients with cirrhosis admitted to intensive care unit. Comparison with current models and CLIF-SOFA score. Am J Gastroenterol 2014; 109(4): 554–562
doi: 10.1038/ajg.2013.466 pmid: 24492755
77 Jalan R, Saliba F, Pavesi M, Amoros A, Moreau R, Ginès P, Levesque E, Durand F, Angeli P, Caraceni P, Hopf C, Alessandria C, Rodriguez E, Solis-Muñoz P, Laleman W, Trebicka J, Zeuzem S, Gustot T, Mookerjee R, Elkrief L, Soriano G, Cordoba J, Morando F, Gerbes A, Agarwal B, Samuel D, Bernardi M, Arroyo V; CANONIC study investigators of the EASL-CLIF Consortium. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol 2014; 61(5): 1038–1047
doi: 10.1016/j.jhep.2014.06.012 pmid: 24950482
78 Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, Laleman W, Trebicka J, Elkrief L, Hopf C, Solís-Munoz P, Saliba F, Zeuzem S, Albillos A, Benten D, Montero-Alvarez JL, Chivas MT, Concepción M, Córdoba J, McCormick A, Stauber R, Vogel W, de Gottardi A, Welzel TM, Domenicali M, Risso A, Wendon J, Deulofeu C, Angeli P, Durand F, Pavesi M, Gerbes A, Jalan R, Moreau R, Ginés P, Bernardi M, Arroyo V; CANONIC Study Investigators of the EASL-CLIF Consortium. Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology 2015; 62(1): 243–252
doi: 10.1002/hep.27849 pmid: 25877702
79 Xie F, Yan L, Lu J, Zheng T, Shi C, Ying J, Shen R, Yang J. Effects of nucleoside analogue on patients with chronic hepatitis B-associated liver failure: meta-analysis. PLoS ONE 2013; 8(1): e54773
doi: 10.1371/journal.pone.0054773 pmid: 23382964
80 Zhang L, Hao CQ, Liu JF, Wang M. Meta-analysis of the short-term effects of lamivudine treatment for severe chronic hepatitis B. Virol J 2013; 10(1): 134
doi: 10.1186/1743-422X-10-134 pmid: 23627972
81 Shi y, HeJQ, Wu W, Huang JR, YangYD, Sheng JF, YuL, Chen Z, Jia HY. The efficacy and safety of nucleos(t)ide analogues in the treatment of HBV-related acute-on-chronic liver failure: a meta-analysis. Ann Hepatol 2013; 12(3): 364–372
pmid: 23619252
82 Rolando N, Clapperton M, Wade J, Wendon J. Administering granulocyte colony-stimulating factor to acute liver failure patients corrects neutrophil defects. Eur J Gastroenterol Hepatol 2000; 12(12): 1323–1328
doi: 10.1097/00042737-200012120-00010 pmid: 11192322
83 Di Campli C, Zocco MA, Saulnier N, Grieco A, Rapaccini G, Addolorato G, Rumi C, Santoliquido A, Leone G, Gasbarrini G, Gasbarrini A. Safety and efficacy profile of G-CSF therapy in patients with acute on chronic liver failure. Dig Liver Dis 2007; 39(12): 1071–1076
doi: 10.1016/j.dld.2007.08.006 pmid: 17964871
84 Spahr L, Lambert JF, Rubbia-Brandt L, Chalandon Y, Frossard JL, Giostra E, Hadengue A. Granulocyte-colony stimulating factor induces proliferation of hepatic progenitors in alcoholic steatohepatitis: a randomized trial. Hepatology 2008; 48(1): 221–229
doi: 10.1002/hep.22317 pmid: 18537187
85 Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, Sarin SK. Granulocyte colony-stimulating factor mobilizes CD34(+) cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology 2012; 142(3): 505–512.e1
doi: 10.1053/j.gastro.2011.11.027 pmid: 22119930
86 Duan XZ, Liu FF, Tong JJ, Yang HZ, Chen J, Liu XY, Mao YL, Xin SJ, Hu JH. Granulocyte-colony stimulating factor therapy improves survival in patients with hepatitis B virus-associated acute-on-chronic liver failure. World J Gastroenterol 2013; 19(7): 1104–1110
doi: 10.3748/wjg.v19.i7.1104 pmid: 23467275
87 Karkhanis J, Verna EC, Chang MS, Stravitz RT, Schilsky M, Lee WM, Brown RS Jr; Acute Liver Failure Study Group. Steroid use in acute liver failure. Hepatology 2014; 59(2): 612–621
doi: 10.1002/hep.26678 pmid: 23929808
88 Zhang XQ, Jiang L, You JP, Liu YY, Peng J, Zhang HY, Xu BY, Mao Q. Efficacy of short-term dexamethasone therapy in acute-on-chronic pre-liver failure. Hepatol Res 2011; 41(1): 46–53
doi: 10.1111/j.1872-034X.2010.00740.x pmid: 20973887
89 Zhao J, Zhang JY, Yu HW, He YL, Zhao JJ, Li J, Zhu YK, Yao QW, Wang JH, Liu HX, Shi SY, Zou ZS, Xu XS, Zhou CB, Wang FS, Meng QH. Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy. Cell Mol Immunol 2012; 9(5): 417–422
doi: 10.1038/cmi.2011.51 pmid: 22231552
90 Chen JF, Wang KW, Zhang SQ, Lei ZY, Xie JQ, Zhu JY, Weng WZ, Gao ZL, Lin BL. Dexamethasone in outcome of patients with hepatitis B virus-related acute-on-chronic liver failure. J Gastroenterol Hepatol 2014; 29(4): 800–806
doi: 10.1111/jgh.12454 pmid: 24224656
91 Mitzner SR, Stange J, Klammt S, Risler T, Erley CM, Bader BD, Berger ED, Lauchart W, Peszynski P, Freytag J, Hickstein H, Loock J, Löhr JM, Liebe S, Emmrich J, Korten G, Schmidt R. Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl 2000; 6(3): 277–286
doi: 10.1053/lv.2000.6355 pmid: 10827226
92 Heemann U, Treichel U, Loock J, Philipp T, Gerken G, Malago M, Klammt S, Loehr M, Liebe S, Mitzner S, Schmidt R, Stange J. Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study. Hepatology 2002; 36(4 Pt 1): 949–958
doi: 10.1053/jhep.2002.36130 pmid: 12297843
93 Sen S, Davies NA, Mookerjee RP, Cheshire LM, Hodges SJ, Williams R, Jalan R. Pathophysiological effects of albumin dialysis in acute-on-chronic liver failure: a randomized controlled study. Liver Transpl 2004; 10(9): 1109–1119
doi: 10.1002/lt.20236 pmid: 15350001
94 Hassanein TI, Tofteng F, Brown RS Jr, McGuire B, Lynch P, Mehta R, Larsen FS, Gornbein J, Stange J, Blei AT. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology 2007; 46(6): 1853–1862
doi: 10.1002/hep.21930 pmid: 17975845
95 Bañares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, Saliba F, Sauerbruch T, Klammt S, Ockenga J, Pares A, Wendon J, Brünnler T, Kramer L, Mathurin P, de la Mata M, Gasbarrini A, Müllhaupt B, Wilmer A, Laleman W, Eefsen M, Sen S, Zipprich A, Tenorio T, Pavesi M, Schmidt HH, Mitzner S, Williams R, Arroyo V; RELIEF study group. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 2013; 57(3): 1153–1162
doi: 10.1002/hep.26185 pmid: 23213075
96 Kribben A, Gerken G, Haag S, Herget-Rosenthal S, Treichel U, Betz C, Sarrazin C, Hoste E, Van Vlierberghe H, Escorsell A, Hafer C, Schreiner O, Galle PR, Mancini E, Caraceni P, Karvellas CJ, Salmhofer H, Knotek M, Ginès P, Kozik-Jaromin J, Rifai K; HELIOS Study Group. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 2012; 142(4): 782–789.e3
doi: 10.1053/j.gastro.2011.12.056 pmid: 22248661
97 Chen Z, Wen T, Zeng Y, Wang L, Lu JJ, Gong S, Tan H, Feng P, Li B, Zhao J, Wang W, Xu M, Yang J, Wu H, Yan L. A single institution experience with living donor liver transplantation for acute-on-chronic hepatitis B liver failure. Hepatogastroenterology 2011; 58(109): 1267–1273
doi: 10.5754/hge10148 pmid: 21937395
98 Bahirwani R, Shaked O, Bewtra M, Forde K, Reddy KR. Acute-on-chronic liver failure before liver transplantation: impact on posttransplant outcomes. Transplantation 2011; 92(8): 952–957
doi: 10.1097/TP.0b013e31822e6eda pmid: 21869735
99 Chan AC, Fan ST, Lo CM, Liu CL, Chan SC, Ng KK, Yong BH, Chiu A, Lam BK. Liver transplantation for acute-on-chronic liver failure. Hepatol Int 2009; 3(4): 571–581
doi: 10.1007/s12072-009-9148-8 pmid: 19680733
100 Liu CL, Fan ST, Lo CM, Wei WI, Yong BH, Lai CL, Wong J. Live-donor liver transplantation for acute-on-chronic hepatitis B liver failure. Transplantation 2003; 76(8): 1174–1179
doi: 10.1097/01.TP.0000087341.88471.E5 pmid: 14578749
101 Duan BW, Lu SC, Wang ML, Liu JN, Chi P, Lai W, Wu JS, Guo QL, Lin DD, Liu Y, Zeng DB, Li CY, Meng QH, Ding HG, Chen XY, Liao HY, Ma LQ, Chen Y, Zhang J, Xiang HP, Duan ZP, Li N. Liver transplantation in acute-on-chronic liver failure patients with high model for end-stage liver disease (MELD) scores: a single center experience of 100 consecutive cases. J Surg Res 2013; 183(2): 936–943
doi: 10.1016/j.jss.2013.03.008 pmid: 23558257
102 Finkenstedt A, Nachbaur K, Zoller H, Joannidis M, Pratschke J, Graziadei IW, Vogel W. Acute-on-chronic liver failure: excellent outcomes after liver transplantation but high mortality on the wait list. Liver Transpl 2013; 19(8): 879–886
doi: 10.1002/lt.23678 pmid: 23696006
103 Kumar R, Krishnamoorthy TL, Tan HK, Lui HF, Chow WC. Change in model for end-stage liver disease score at two weeks, as an indicator of mortality or liver transplantation at 60 days in acute-on-chronic liver failure. Gastroenterol Rep (Oxf) 2015; 3(2): 122–127
doi: 10.1093/gastro/gou075 pmid: 25391261
104 Rolando N, Harvey F, Brahm J, Philpott-Howard J, Alexander G, Gimson A, Casewell M, Fagan E, Williams R. Prospective study of bacterial infection in acute liver failure: an analysis of fifty patients. Hepatology 1990; 11(1): 49–53
doi: 10.1002/hep.1840110110 pmid: 2295471
105 Rolando N, Harvey F, Brahm J, Philpott-Howard J, Alexander G, Casewell M, Fagan E, Williams R. Fungal infection: a common, unrecognised complication of acute liver failure. J Hepatol 1991; 12(1): 1–9
doi: 10.1016/0168-8278(91)90900-V pmid: 2007764
106 Wang ZX, Yan LN, Wang WT, Xu MQ, Yang JY. Impact of pretransplant MELD score on posttransplant outcome in orthotopic liver transplantation for patients with acute-on-chronic hepatitis B liver failure. Transplant Proc 2007; 39(5): 1501–1504
doi: 10.1016/j.transproceed.2007.02.070 pmid: 17580172
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