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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number106100
Issue number3
StatePublished - Mar 17 2023


  • Human metabolism
  • Microbiome
  • Virology

ASJC Scopus subject areas

  • General


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