A case of severe liver injury due to hepatitis B virus-related immune reconstitution inflammatory syndrome following HIV treatment reinitiation: diagnosis by liver biopsy

BACKGROUND: HIV and HBV frequently coexist, with an estimated 8% prevalence of chronic HBV among people living with HIV (PLWH). In profoundly immunosuppressed PLWH, initiation or reinitiation of antiretroviral therapy (ART) can trigger immune reconstitution inflammatory syndrome (IRIS). When directed against HBV, IRIS can manifest as a hepatic flare (IRIS-HF). The long-term clinical implications of IRIS-HF remain incompletely understood. CASE PRESENTATION: We describe a 42-year-old man with HIV/HBV coinfection who had discontinued ART for one year. On ART reinitiation with bictegravir/emtricitabine/tenofovir alafenamide, his CD4 count was 2.3 cells/µL and HIV RNA was 4.8 × 10⁵ copies/mL. Five weeks later, he developed a severe hepatic flare (AST 987 U/L, ALT 968 U/L). The differential diagnosis included HBV-related IRIS, opportunistic infections (CMV hepatitis, disseminated MAC, EBV-associated lymphoma), and drug-induced liver injury. A liver biopsy revealed fatty degeneration and lymphocytic infiltration, consistent with HBV-related IRIS. Transaminases normalized by week 11. He subsequently achieved HBsAg loss with anti-HBs seroconversion within 2 years after ART reinitiation. CONCLUSION: This case illustrates HBV flare due to IRIS following ART reinitiation in a profoundly immunosuppressed patient. The subsequent HBsAg loss suggests that IRIS-HF may promote HBV clearance, highlighting its potential role in achieving a functional cure. Vigilant monitoring of liver function is essential during ART initiation or reinitiation in HIV/HBV coinfected individuals.