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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
REVIEW |
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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Abstract  

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:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-016-0439-x     OR     http://academic.hep.com.cn/fmd/EN/Y2016/V10/I1/1
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)
CMA* APASL EASL-AASLD
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.
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