Occult Hepatitis B Infection

Occult hepatitis B virus infection (OBI) is characterized by detection of HBV DNA in liver and/or serum despite negative serum HBsAg, representing a heterogeneous group with diverse pathogenetic mechanisms. It is increasingly recognized due to widespread use of highly sensitive PCR assays. Two main forms exist: seropositive OBI (anti-HBc and/or anti-HBs positive) and seronegative OBI (all serological markers negative—rare).

Pathogenesis includes integration of HBV DNA into hepatocyte genome, very low-level viral replication below assay detection thresholds, mutations in S gene reducing HBsAg expression or causing escape from current commercial assays, and host immune control suppressing viral replication. HBV DNA in occult infection persists as covalently closed circular DNA (cccDNA) in hepatocyte nuclei, providing a stable template for reactivation under appropriate conditions. Prevalence varies by population: <1% in healthy blood donors, 10-30% in HCV coinfected, up to 45% in HIV coinfected, and higher in cirrhosis and HCC patients.

Clinical implications include risk of reactivation during immunosuppression (chemotherapy, especially rituximab, hematopoietic stem cell transplantation, organ transplantation, anti-TNF biologics)—reactivation can lead to severe hepatitis flare, liver failure, and death; transmission via blood transfusion (now reduced by NAT screening), organ transplantation, and rarely sexual or perinatal routes; and possible contribution to hepatocarcinogenesis through ongoing low-level inflammation and integrated viral DNA. Management strategies include screening anti-HBc in high-risk patients before immunosuppression, prophylactic antiviral therapy (entecavir, tenofovir) in selected cases, monitoring during therapy, and consideration in evaluation of cryptogenic hepatitis or HCC.