Hepatocyte-Derived L-Carnitine Restricts Hepatitis B Surface Antigen Loss Through an Immunosuppressive Effect on Germinal Center–Related Immune Cells

Abstract

Abstract Background The outcome of hepatitis B virus (HBV) infection is significantly affected by host immune response; herein, we aim to dissect the effect of L-carnitine (L-Cn) on germinal center (GC)–related immune cells and the influence on the prognosis of HBV infection. Methods In vitro and in vivo experiments were performed in patients with chronic HBV infection and a hydrodynamic injection mouse model. Results In vitro assays revealed that L-Cn significantly reduced GC-related immune responses and enhanced immunosuppressive profiles. Intriguingly, L-Cn released from lysed hepatocytes was associated with the degree of liver damage. Besides, the administration of L-Cn in an HBV mouse model resulted in delayed clearance of hepatitis B surface antigen (HBsAg) in serum and decreased GC formation in the spleen. Notably, patients with HBsAg loss showed decreased plasma L-Cn levels, and longitudinal observations found that low baseline levels of L-Cn were associated with a favorable treatment response in patients with chronic hepatitis B. Conclusions The suppressive effect of hepatocyte-derived L-Cn on GC-related immune cells may contribute to the inability of HBsAg clearance in chronic HBV infection, indicating that L-Cn might serve as a potential therapeutic target for the treatment of HBV infection.