S5949 Concurrent HBsAg and Anti-HBs Positivity in Chronic Hepatitis B: Atypical Serologic Profile Raising Concern for Immune Escape Variants

Introduction: Hepatitis B Virus (HBV) infection is the most common infectious cause of chronic hepatitis, and management is typically based on its well-characterized serological course. Presence of HBsAg, HBV DNA, HBeAg and anti-Hbc IgM indicate acute infection, while presence of Anti-HBs and Anti-HBe indicate recovery. Rarely, patients have been documented to present with atypical serological profiles, complicating management. We present a case of a patient with prolonged concurrent HBsAg and anti-HBs positivity in the absence of liver fibrosis or dysfunction, a presentation that raises diagnostic and management challenges. Case Description/Methods: The patient is a 47-year-old Hispanic man with a history of unspecified hepatitis presented in 2019 for GERD. He denied a history of alcohol use, intravenous drug use, or multiple sexual partners. Evaluation was unremarkable, and he was lost to follow-up. Serology workup during 2020-2021 revealed positive HBV DNA, anti-HBe, and concurrent HBsAg and anti-HBs. However, liver ultrasound revealed only mild hepatic steatosis and LFTs were within normal limits. Given low HBV DNA titer and normal LFTs, treatment was deferred. The patient was lost to follow-up after 2022, returning in 2024 with epigastric pain. HBV serology continued to demonstrate persistent positive HBsAg, anti-HBs and HBV DNA. Liver elastography and needle core biopsy demonstrated chronic hepatitis without fibrosis, steatosis or significant inflammation (METAVIR F0-F1; Batts-Ludwig Grade 0, Stage 0). Immunostain for HBsAg was negative. Biopsy demonstrated no structural abnormalities, and iron, copper, reticulin, trichrome, PAS with diastase stains were normal. Discussion: This patient’s atypical HBV serologic profile and low-level viremia in the absence of liver fibrosis represent a diagnostic scenario that may reflect low-replicative chronic infection. The patient’s persistent HBsAg raises the possibility of impaired immune clearance, or immune escape variants. Although genotypic confirmation was not pursued, future genotypic analysis may help identify immune escape and preC/C variants in the case of declining liver function, to guide therapeutic options.