Background:  Transient liver enzyme elevation is frequently described in HIV-infected patients under ART, especially in the setting of viral hepatitis co-infection. However, risk factors of acute cytolysis or cholestasis in HIV/hepatitis B virus (HBV) -co-infected patients are poorly described. The objective of this study was to characterize those risk factors with a focus on the role of ART.

Methods:  Included patients were from a 3-year prospective French multi-center cohort of HIV-infected patients with chronic HBV co-infection (plasma hepatitis B surface antigen [HBsAg] was detected at inclusion). A multivariate Markovian modeling approach was used to describe and to identify independent risk factors of transient severe (ACTG grade 3 or 4) cytolysis and cholestasis in 300 HIV/HBV-co-infected patients.

Results:  Severe cytolysis and cholestasis incidence were 5.0 (95%CI 2.5 to 7.5) and 6.7 (95%CI 3.9 to 9.5) cases for 100 patients-years, respectively. Independent risk factors were:  concurrent chronic hepatitis Delta virus (HDV) co-infection (HR 8.35, 95%CI 1.44 to 48.50), HBV genotype G (HR 3.87 95%CI 1.17 to 12.79), and age (HR 0.33 95%CI 0.12 to 0.88) for severe cytolysis; HBV infection duration longer than 5 years (HR 3.47, 95%CI 1.63 to 7.41) and high alcohol consumption (which decreases the rate of acute cholestasis disappearance) (HR 0.38, 95%CI 0.21 to 0.70). When focusing on HAART, no drug  class was associated with a higher incidence of severe cytolysis,  but protease inhibitors (PI) appeared to be independently associated with increased rates of severe cholestasis (HR 2.11, 95%CI 1.20 to 3.73).

Conclusions:  Transient episodes of cytolysis or cholestasis in HIV/HBV-co-infected patients were common and mostly associated with patient- and virus-related risk factors rather than ART classes. The effect of ART was only noted in terms of increased occurrence of severe cholestasis in case of treatment with PI.