Apolipoprotein H induces sex-specific steatohepatitis and gut dysbiosis during chronic hepatitis B infection
Yaming Liu,
Yangtao Wu,
Xiaoming Jiang,
Bo Chen,
Jing Lu,
Zexin Cai,
Baorong Fu,
Wei Zheng,
Ruihong Wu,
Gang Chen,
Shulan Tian,
Jianlin Ren
Affiliations
Yaming Liu
Department of Gastroenterology and Hepatology, Xiamen University Zhongshan Hospital, Xiamen, Fujian Province 361001, China; Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China
Yangtao Wu
Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China; National Institute of Diagnostic and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, Fujian Province 361001, China
Xiaoming Jiang
Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province 132001, China
Bo Chen
Department of Hepatobiliary Surgery, The first affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China
Jing Lu
Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China
Zexin Cai
Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China
Baorong Fu
Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China; National Institute of Diagnostic and Vaccine Development in Infectious Disease, Xiamen University, Xiamen, Fujian Province 361001, China
Wei Zheng
Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China; Department of Pathology, Xiamen University Zhongshan Hospital, Xiamen, Fujian Province 361001, China
Ruihong Wu
Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin Province 132001, China
Gang Chen
Department of Hepatobiliary Surgery, The first affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, China
Shulan Tian
Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USA
Jianlin Ren
Department of Gastroenterology and Hepatology, Xiamen University Zhongshan Hospital, Xiamen, Fujian Province 361001, China; Department of Digestive Diseases, School of Medicine, Xiamen University, Xiamen, Fujian Province 361001, China; Corresponding author
Summary: Apolipoprotein H (APOH) is involved in lipid metabolism and functions as an acute-phase protein during hepatitis B virus (HBV) infection. Herein, we explored whether APOH acts on the development of fatty liver upon chronic HBV infection. Serum APOH level was significantly lower in cirrhosis patients than in healthy controls or patients with chronic infection. It showed sex bias, with elevated levels in female patients with chronic infection. Also, serum APOH levels were negatively correlated with HBV surface antigen (HBsAg) but positively correlated with albumin and triglyceride levels. In In vitro HBV infection model, HBV upregulated APOH expression in a non-temporal manner, and HBsAg levels were elevated by silencing APOH. RNA sequencing (RNA-seq) demonstrated bidirectional expression of APOH, which impacted the immunoregulation upon infection or the metabolic regulation in HepG2.2.15 cells. Then, ApoH−/− mice with persistent HBV replication displayed steatohepatitis and gut microbiota dysbiosis with synergistic sex differences. Our study deciphers the roles of APOH in chronic liver diseases.
