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

## TL;DR

A man with HIV and hepatitis B virus experienced severe liver injury after restarting HIV treatment, which was diagnosed as immune reconstitution inflammatory syndrome and led to hepatitis B surface antigen loss.

## Contribution

This case highlights IRIS-related hepatic flare as a potential pathway for HBV clearance in coinfected individuals.

## Key findings

- Liver biopsy confirmed HBV-related IRIS in a patient with severe hepatic flare after ART reinitiation.
- The patient achieved HBsAg loss and anti-HBs seroconversion within two years of ART reinitiation.
- IRIS-HF may contribute to HBV clearance and functional cure in HIV/HBV coinfected individuals.

## Abstract

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.

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.

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.