D3.486 - Acute hepatitis B with atypical serological markers in a previously vaccinated patient receiving anti-CD20 obinutuzumab

BACKGROUND: Acute hepatitis B primoinfection or reactivation is a potentially life-threatening complication in patients receiving B-cell-depleting therapies. Obinutuzumab, an anti-CD20 monoclonal antibody used in B-cell malignancies, induces profound and sustained B-cell depletion, which can ablate the production of HBV-specific antibodies generating atypical serological profiles that may critically delay diagnosis.

CASE: A 71-year-old woman under active hematological follow-up presented to the hospital after routine bloodwork revealed elevated liver enzymes. Laboratory findings demonstrated severe hepatocellular injury with Aspartate Aminotransferase at 916 U/L and Alanine Aminotransferase at 1957 U/L, alongside mild cholestasis evidenced by elevated GGT (243 U/L) and alkaline phosphatase (226 U/L).

The patient reported no recent modification of her regular medications and denied acute alcohol intake, recent travel, or fever. General condition was preserved, with only mild asthenia reported. Abdominal ultrasound examination revealed a morphologically normal liver with no intrahepatic or extrahepatic biliary duct dilation, no focal hepatic lesion, no signs of portal hypertension, thereby excluding structural or obstructive etiologies.

Comprehensive infectious serology screening was performed and returned negative for all tested agents, with the exception of hepatitis B virus (HBV) markers. The serological profile was atypical: anti-HBs antibodies were detected at a protective concentration alongside a positive hepatitis B surface antigen (HBsAg) and positive HB e antigen, while both IgG and IgM anti-HBc antibodies were undetectable (automated chemiluminescence assay). Given this paradoxical pattern, an HBV viral load was performed, revealing massive viral replication exceeding 10⁹ copies/mL. Antiviral therapy combining tenofovir disoproxil fumarate and emtricitabine was promptly initiated and major clinical improvement appeared.

CONCLUSION: This case highlights an acute, massive HBV replication with profound B-cell depletion due to anti-CD20 obinutuzumab therapy. Obinutuzumab-induced B-cell depletion resulted in an atypical serological profile, characterized by the absence of core antibodies (anti-HBc) despite the presence of surface antibodies (anti-HBs) due to prior vaccination. This underscores the importance of performing HBV DNA viral load testing in profoundly immunocompromised patients presenting with acute hepatitis, in the era of potent B-cell-depleting therapies.