Alcohol induces intrahepatic humoral immunity-related suppression and delays the clearance of HBV infection

Alcohol consumption is widespread. As the main organ of alcohol metabolism, the liver also has an immune tolerance function. However, little is known about how alcohol affects intrahepatic immune dysregulation and hepatitis B virus (HBV) infection. In a mice model, alcohol intake increased Fas expression on intrahepatic B220+B cells and intrahepatic CD138+B cells, increased TGF-beta and IL-10 production by intrahepatic CD19+B cells, and decreased frequencies of intrahepatic T peripheral helper (Tph) cells and intrahepatic T follicular helper (Tfh) cells. Tph cells, but not Tfh cells, were negatively correlated with the B-lineage cell-related apoptosis and the production of immunosuppressive cytokines. Besides, alcohol intake significantly reduced the production of IL-21 by Tfh-like cells and CD8+PD-1+ cells and reduced the area of the splenic germinal center B cells. After 4 weeks of alcohol intake, we induced HBV infection in mice by injecting plasmid pAAV-HBV1.2. Alcohol intake increased serum hepatitis B surface antigen (HBsAg) and hepatitis B envelope antigen levels, delayed HBsAg clearance and decreased anti-HBsAg antibodies production at 40 days post-injection. In conclusion, our study reveals that alcohol intake can suppress humoral immunity and impede HBV clearance, providing further evi-dence for alcohol abstinence in patients with HBV infection.