Apolipoprotein H induces sex-specific steatohepatitis and gut dysbiosis during chronic hepatitis B infection.

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 HBV infection model, HBV upregulated expression in a non-temporal manner, and levels were elevated by silencing . RNA sequencing (RNA-seq) demonstrated bidirectional expression of which impacted the immunoregulation upon infection or the metabolic regulation in HepG2.2.15 cells. Then, 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.