HBV transmission from HBcAb-positive mothers: insights from pediatric liver transplantation studies

Hepatitis B core antibody (HBcAb) is a marker of past or ongoing hepatitis B virus (HBV) infection and is frequently investigated in the context of occult HBV infection (OBI). While vertical transmission from mothers with OBI is recognized, the risk of transmission from mothers who are HBcAb-positive (HBsAg-negative) remains unclear. This study primarily aimed to directly assess the risk of HBV transmission from HBcAb-positive mothers to their children through the analysis of liver tissue samples. As an initial step, we characterized the prevalence of HBcAb in children born to these mothers. Our study employed a two-phase design. First, to establish the epidemiological context, we conducted a large-scale cross-sectional serological survey to determine the prevalence and decay kinetics of passively transferred maternal HBcAb in children. Second, to directly investigate the primary research question, we analyzed liver tissues from a distinct cohort of 49 pediatric transplant recipients (born to HBcAb-positive, HBsAg-negative mothers) retrieved from our institutional biobank. These samples were tested for intrahepatic HBV DNA using highly sensitive droplet digital PCR (ddPCR) and nested PCR. The serological survey showed that passively acquired maternal HBcAb was present in 41.4% of newborns at birth and waned over several months. In the liver tissue analysis, intrahepatic HBV DNA was detected in 10 of the 49 pediatric transplant recipients (20.4%), providing direct evidence of occult infection. Our findings suggest that vertical transmission from mothers who are HBcAb-positive but HBsAg-negative may represent a potential, underrecognized pathway for OBI in infants. These results underscore the need for further research to clarify the transmission risks associated with maternal HBcAb status to better inform prevention strategies in HBV high-endemicity regions.