title: Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation.
abstract: OBJECTIVE
  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.
authors: 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.
authors: Hai
authors: H
authors: Li
authors: Department of Liver Surgery and Liver Transplantation, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Qiang
authors: Q
authors: Xia
authors: 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.
authors: Bo
authors: B
authors: Zeng
authors: 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.
authors: Shu-Ting
authors: ST
authors: Li
authors: 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.
authors: Heng
authors: H
authors: Liu
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Qi
authors: Q
authors: Li
authors: Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Jun
authors: J
authors: Li
authors: 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.
authors: Shu-Yin
authors: SY
authors: Yang
authors: 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.
authors: Xiao-Jun
authors: XJ
authors: Dong
authors: 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.
authors: Ting
authors: T
authors: Gao
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Stefan
authors: S
authors: Munker
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Yan
authors: Y
authors: Liu
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
authors: Roman
authors: R
authors: Liebe
authors: Department of Liver Surgery and Liver Transplantation, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Feng
authors: F
authors: Xue
authors: Department of Liver Surgery and Liver Transplantation, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Qi-Gen
authors: QG
authors: Li
authors: Department of Liver Surgery and Liver Transplantation, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Xiao-Song
authors: XS
authors: Chen
authors: Department of Pathology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Qiang
authors: Q
authors: Liu
authors: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors: Hui
authors: H
authors: Zeng
authors: Department of Gastroenterology, Zhong-shan Hospital, Fu Dan University, Shanghai, China.
authors: Ji-Yao
authors: JY
authors: Wang
authors: Department of Infectious Disease, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Qing
authors: Q
authors: Xie
authors: Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors: Qin-Hua
authors: QH
authors: Meng
authors: Severe Hepatitis Department & Intensive Care Unit, Shanghai Public Health Center, Affiliated Fudan University, Shanghai, China.
authors: Jie-Fei
authors: JF
authors: Wang
authors: Department of Nephrology and Hypertension, Otto-von-Guericke-University, Magdeburg, Germany.
authors: Peter R
authors: PR
authors: Mertens
authors: Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
authors: Frank
authors: F
authors: Lammert
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Manfred V
authors: MV
authors: Singer
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Steven
authors: S
authors: Dooley
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: Matthias P A
authors: MP
authors: Ebert
authors: 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.
authors: De-Kai
authors: DK
authors: Qiu
authors: Department of Pathology, Beijing China-Japan Friendship Hospital, Beijing, China. Electronic address: wang_tailing@126.com.
authors: Tai-Ling
authors: TL
authors: Wang
authors: Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: honglei.weng@medma.uni-heidelberg.de.
authors: Hong-Lei
authors: HL
authors: Weng
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000175:diagnosis* / Q000601:surgery; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006510:Hepatitis B Antibodies / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000175:diagnosis*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000175:diagnosis; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D006510:Hepatitis B Antibodies
keywords: Acute decompensation; Acute-on-chronic liver failure; Cirrhosis; HBV; Liver histology; Submassive hepatic necrosis