Hepatic Flare Following Effective Antiretroviral Therapy Is Associated With HBsAg Seroclearance in HBV/HIV‐1 Co‐Infection

Little is known about the clinical significance of hepatic flare following effective antiretroviral therapy (ART) on HBsAg seroclearance and prognosis in HBV/HIV co-infection. This observational cohort study recruited HBV/HIV-1 co-infected patients from the China National Free Antiretroviral Treatment Program. We obtained longitudinal information on demographic characteristics, clinical indicators, and treatment outcomes. Hepatic flare was defined as an elevation of ALT of more than five times the upper limit of the normal range without an upsurge of HBV DNA or HBsAg at any time point between ART initiation and 12 months. Among the 1354 enrolled patients, 98.7% received two anti-HBV drugs containing ART and 95.1% achieved good viral control. Hepatic flare was observed in 88 (6.5%) patients and was more frequent in those with lower baseline immune function but subsequently enhanced immune reconstitution. Over a median follow-up of 4.7 years, we observed 99 HBsAg seroclearance, 9 hepatic events, 6 HIV-associated malignancy, 3 non-HIV-associated malignancy, and 3 all-cause mortality. The 3-, 5-, and 10-year cumulative incidence of HBsAg seroclearance was 6.4%, 8.9%, and 12.9%, respectively. Compared to patients without hepatic flare, patients with hepatic flare had significantly higher rates of HBsAg seroclearance (13.6% vs. 6.9%, p = 0.018) but had no recorded adverse outcome. Multivariate analysis with different models indicated that hepatic flare was independently associated with HBsAg seroclearance especially in patients with low immune function, normal ALT, and high levels of HBV DNA and HBsAg at baseline. In HBV/HIV-1 co-infection, hepatic flare following effective ART is associated with HBsAg seroclearance. HBV-specific T cells immune reconstitution may represent a potential mechanism which deserves further investigation.