Breaking the serologic rule: chronic hepatitis B with simultaneous HBsAg and anti-HBs positivity-a case report

Chronic hepatitis B virus (HBV) infection continues to pose a significant global disease burden, because of its potential progression to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, more than 250 million individuals are estimated to be living with chronic HBV infection. Under standard serologic interpretation, the presence of hepatitis B surface antigen (HBsAg) signifies ongoing infection, whereas antibodies to hepatitis B surface antigen (anti-HBs) are generally associated with viral clearance or protective immunity. The simultaneous presence of both markers is rare and may lead to misinterpretation of serologic results, particularly when identified incidentally during routine screening in a primary care settings.

We describe a 60-year-old Saudi woman with an asymptomatic chronic HBV infection incidentally identified during routine pre-colonoscopy screening in a primary care setting. Laboratory testing revealed reactive HBsAg, total anti-HBc positivity, reactive anti-HBs titer, and HBV DNA level was 275 IU/mL consistent with low-level viremia. Liver enzymes were mildly elevated on prior testing subsequently normalized on follow- up. Transient elastography demonstrated no evidence of hepatic fibrosis or steatosis. The patient had no history of HBV vaccination, blood transfusions, liver disease, or recognized high-risk exposures, including intravenous drug use or high-risk sexual or household contact.

This case highlights a diagnostic pitfall in HBV serology, as concurrent HBsAg and anti-HBs positivity does not indicate viral clearance and may reflect immune escape mutations, viral heterogeneity, or host immune factors. Recognition of this rare serologic profile is particularly important for primary care physicians, as accurate interpretation requires integration of serologic, virologic, and clinical data, particularly in asymptomatic patients identified through routine screening. This ensure appropriate diagnosis, long-term surveillance, and risk stratification. Clinicians should remain vigilant when encountering this rare serologic profile to guide appropriate referral and follow-up.