Hai Li1, Qiang Xia2, Bo Zeng3, Shu-Ting Li3, Heng Liu4, Qi Li5, Jun Li6, Shu-Yin Yang3, Xiao-Jun Dong3, Ting Gao3, Stefan Munker5, Yan Liu5, Roman Liebe7, Feng Xue2, Qi-Gen Li2, Xiao-Song Chen2, Qiang Liu8, Hui Zeng9, Ji-Yao Wang10, Qing Xie11, Qin-Hua Meng12, Jie-Fei Wang13, Peter R Mertens14, Frank Lammert15, Manfred V Singer5, Steven Dooley5, Matthias P A Ebert5, De-Kai Qiu3, Tai-Ling Wang16, Hong-Lei Weng17. 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.
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.
Authors: Zhe Shen; Yan Liu; Bedair Dewidar; Junhao Hu; Ogyi Park; Teng Feng; Chengfu Xu; Chaohui Yu; Qi Li; Christoph Meyer; Iryna Ilkavets; Alexandra Müller; Carolin Stump-Guthier; Stefan Munker; Roman Liebe; Vincent Zimmer; Frank Lammert; Peter R Mertens; Hai Li; Peter Ten Dijke; Hellmut G Augustin; Jun Li; Bin Gao; Matthias P Ebert; Steven Dooley; Youming Li; Hong-Lei Weng Journal: Am J Pathol Date: 2016-05-10 Impact factor: 4.307
Authors: Hong-Lei Weng; Xiaobo Cai; Xiaodong Yuan; Roman Liebe; Steven Dooley; Hai Li; Tai-Ling Wang Journal: Front Physiol Date: 2015-06-16 Impact factor: 4.566
Authors: Mark J W McPhail; Debbie L Shawcross; Matthew R Lewis; Iona Coltart; Elizabeth J Want; Charalambos G Antoniades; Kiril Veselkov; Evangelos Triantafyllou; Vishal Patel; Oltin Pop; Maria Gomez-Romero; Michael Kyriakides; Rabiya Zia; Robin D Abeles; Mary M E Crossey; Wayel Jassem; John O'Grady; Nigel Heaton; Georg Auzinger; William Bernal; Alberto Quaglia; Muireann Coen; Jeremy K Nicholson; Julia A Wendon; Elaine Holmes; Simon D Taylor-Robinson Journal: J Hepatol Date: 2016-01-18 Impact factor: 25.083