Circulating HBV RNA and hepatitis B core-related antigen trajectories in persons with HIV/HBV coinfection and HBsAg loss on tenofovir therapy. The Journal of Infectious Diseases
Novel hepatitis B virus (HBV) serum markers have improved our understanding of the HBV replication cycle. Among these markers, hepatitis B core-related antigen (HBcrAg) serves as a surrogate for measuring the molecular reservoir of covalently closed circular DNA (cccDNA) within hepatocytes, while circulating HBV RNA indicates ongoing cccDNA transcriptional activity during antiviral therapy.
In a new study, Begré et al. explored the trajectories and potential roles of these markers in individuals with HBV and HIV coinfection who achieved hepatitis B surface antigen (HBsAg) loss, a marker of functional cure. The study measured HBcrAg and HBV RNA levels in participants from the Swiss HIV Cohort Study who were receiving tenofovir-based antiretroviral therapy, and compared their trajectories between 29 individuals who achieved functional cure, and 29 matched individuals who remained HBsAg positive.
Over a median follow-up of 12 years, HBsAg loss occurred after a median of 4 years (interquartile range 1-8). All participants who achieved HBsAg loss reached undetectable HBV RNA levels during tenofovir-based therapy, with undetectable HBV RNA levels observed prior to HBsAg loss. In contrast, among those who did not achieve HBsAg loss, only 79% reached undetectable HBV RNA levels while on tenofovir-based therapy. Persistent HBcrAg levels were observed in 34% of individuals who achieved HBsAg loss and in 48% of those who did not.
The study highlights that undetectable HBV RNA consistently preceded HBsAg loss in individuals who achieved a functional cure, while those who did not achieve HBsAg loss were less likely to reach undetectable HBV RNA levels. Additionally, persistent HBcrAg levels were more common in individuals without HBsAg loss, suggesting ongoing low-level cccDNA translation despite tenofovir-based therapy. The clinical significance of this ongoing transcriptional activity, including its potential role in liver-related outcomes such as hepatocellular carcinoma, remains to be determined.