Prevalence of Occult Infection by Hepatitis B Virus in Liver Biopsies in Clinical Practice

Occult hepatitis B infection (OBI) is defined by detectable hepatitis B virus (HBV) DNA in liver tissue in the absence of hepatitis B surface antigen (HBsAg) and remains insufficiently characterized in low-endemic European settings. This study aimed to determine the prevalence of OBI using direct HBV DNA detection in liver tissue in a real-world cohort of patients undergoing diagnostic liver biopsy. This observational study included consecutive HBsAg-negative patients who underwent liver biopsy between 2020 and 2023. HBV DNA in liver tissue was quantified by real-time PCR, and clinical and serological data were collected. A total of 86 patients were included. OBI was identified in 4 patients (4.7%). All OBI cases were anti-HBc-positive, and two were also anti-HBs-positive. No cases of seronegative OBI were detected. OBI was observed across different underlying liver disease etiologies, including viral, metabolic, autoimmune, and cholestatic conditions. In conclusion, OBI was infrequent in this cohort and consistently associated with anti-HBc seropositivity. These findings suggest that anti-HBc may help identify individuals with prior HBV exposure in whom occult infection can be detected in liver tissue in low-prevalence settings.