Changes in HBcAg and HBsAg Expression Following Antiviral Therapy and Their Role in Outcome of Patients with Chronic Hepatitis B.

Background: Hepatitis B core antigen (HBcAg) and surface antigen (HBsAg) can be detected through immunostaining of liver tissue. This study examined the extent and patterns of HBcAg and HBsAg staining before and after long-term nucleos(t)ide analogue (NA) therapy.

Methods: Liver biopsies performed before and after 4 years of NA treatment were analyzed from patients with HBeAg-positive and HBeAg-negative chronic hepatitis B participating in 3 treatment trials. Immunostaining for HBcAg and HBsAg was evaluated using semi-quantitative scales for both extent and distribution. HBV DNA, HBV RNA, HBeAg status and quantitative HBsAg (qHBsAg), were correlated with changes in immunostaining. Baseline HBcAg and HBsAg staining were correlated with clinical outcomes.

Results: 91 patients had a pre-treatment biopsy, and 81 had paired pre-treatment and year 4 biopsies. Pre-treatment, three-quarters were positive for HBcAg, predominantly in a cytoplasmic staining pattern, and 86% had detectable HBsAg, with 79% exhibiting a scattered granular pattern. Following 4 years of NA treatment, the proportion of biopsies without HBcAg staining increased from 26% to 63% and HBsAg staining from 14% to 26%, compared to baseline. Inhibition of replication was associated with a significant decline in HBcAg staining and loss of HBcAg staining was related to the duration of replication inhibition. In contrast, long-term NA therapy had minimal effect on extent of HBsAg staining. The absence of contiguous granular HBsAg pattern was associated with HBsAg loss.

Conclusions: NA-related inhibition of viral replication was associated with marked reduction in HBcAg expression in HBeAg-positive and HBeAg-negative patients but minimal changes in extent of HBsAg staining, likely reflecting HBsAg production from integrated HBV DNA.