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J Hepatol. 2015 Jul;63(1):50-9. doi: 10.1016/j.jhep.2015.01.029. Epub 2015 Jan 31.

Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation.

Author information

1
Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Digestive Disease, Shanghai, China; Key Laboratory of Gastroenterology & Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China. Electronic address: haili_17@126.com.
2
Department of Liver Surgery and Liver Transplantation, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
3
Department of Gastroenterology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Digestive Disease, Shanghai, China; Key Laboratory of Gastroenterology & Hepatology, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China.
4
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
5
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
6
Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
7
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
8
Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
9
Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
10
Department of Gastroenterology, Zhong-shan Hospital, Fu Dan University, Shanghai, China.
11
Department of Infectious Disease, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
12
Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China.
13
Severe Hepatitis Department & Intensive Care Unit, Shanghai Public Health Center, Affiliated Fudan University, Shanghai, China.
14
Department of Nephrology and Hypertension, Otto-von-Guericke-University, Magdeburg, Germany.
15
Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
16
Department of Pathology, Beijing China-Japan Friendship Hospital, Beijing, China. Electronic address: wang_tailing@126.com.
17
Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: honglei.weng@medma.uni-heidelberg.de.

Abstract

BACKGROUND & AIMS:

Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence.

METHODS:

A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses.

RESULTS:

SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p<0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN.

CONCLUSIONS:

SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease.

KEYWORDS:

Acute decompensation; Acute-on-chronic liver failure; Cirrhosis; HBV; Liver histology; Submassive hepatic necrosis

PMID:
25646889
DOI:
10.1016/j.jhep.2015.01.029
[Indexed for MEDLINE]

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