Serum O-Glycosylated Hepatitis B Surface Antigen Levels in Patients with Chronic Hepatitis B During Nucleos(t)ide Analog Therapy

Abstract Serum hepatitis B surface antigen (HBsAg) is a component of hepatitis B virus (HBV) virions and non-infectious subviral particles (SVPs). O -glycosylation of the PreS2 domain of middle HBsAg protein is a distinct characteristic of genotype C HBV virions versus SVPs. We measured serum O -glycosylated HBsAg levels in 47 treatment-naïve patients with genotype C chronic hepatitis B (CHB) at baseline and after 48 weeks of nucleos(t)ide analog (NA) therapy by immunoassay using a monoclonal antibody against the O-glycosylated PreS2 domain of middle HBsAg, and analyzed their correlations with conventional HBV marker levels. At baseline, serum O -glycosylated HBsAg levels were significantly correlated with HBV DNA, HBsAg, and hepatitis B-core related antigen (HBcrAg) levels. HBV DNA and O -glycosylated HBsAg levels were decreased after 48 weeks of NA therapy. The correlation between O -glycosylated HBsAg and HBsAg or HBcrAg levels was lost in patients who achieved undetectable HBV DNA. HBV DNA and RNA were detected in the O -glycosylated HBsAg-binding serum fraction, and the proportion of HBV RNA increased during NA therapy. In conclusion, serum O -glycosylated HBsAg levels change during NA therapy and may reflect combined serum HBV DNA and RNA virion levels, and an O -glycosylated HBsAg-based immunoassay may allow monitoring viral kinetics during NA therapy.