Immunopathogenesis of Hepatic Flare in HIV/Hepatitis B Virus (HBV)-Coinfected Individuals after the Initiation of HBV-Active Antiretroviral Therapy

Background. The pathogenesis of and risk factors for hepatic flare (HF) after the initiation of hepatitis B virus (HBV)-active antiretroviral therapy (ART) in HIV/HBV-coinfected individuals is not well understood. Methods. We studied HF in ART-naive HIV/HBV-coinfected individuals in Thailand (n = 36) who were beginning HBV-active ART as part of a prospective clinical trial. HF was defined as an alanine aminotransferase (ALT) level >5 times the upper limit of normal or >200 IU/L higher than that at baseline. Immune mediators (interleukin [IL]-18, IL-2, IL-6, IL-8, IL-10, soluble CD26 [sCD26], sCD30, sCD8, CXCL-10, CCL-2, tumor necrosis factor-alpha, interferon [IFN]-gamma, and IFN-alpha) and activated NK cells were quantified. Results. HBV DNA and ALT levels at baseline were higher in patients with HF (n = 8) than in patients without HF (n = 28) (P = .01). After the initiation of ART, CXCL-10 levels remained elevated in patients with HF but decreased in patients without HF (P < .01). sCD30 levels increased and were significantly higher at week 8 in patients with HF (P < .05). There was a positive correlation between levels of ALT and levels of CXCL-10, sCD30, CCL-2, and IL-18 at week 8 (the time of peak ALT level) but not at other time points. Conclusion. Elevated HBV DNA and ALT levels before the initiation of HBV-active ART are risk factors for HF. The pathogenesis of HF after the initiation of HBV-active ART is probably consistent with immune restoration disease.