ALT Flares in HIV-HBV Coinfected Patients after Starting Antiretroviral Therapy

By Liz Highleyman

People with chronic hepatitis B virus (HBV) infection may experience "flares" or sudden increases in blood levels of alanine transaminase (ALT), an enzyme that indicates liver inflammation. Among HIV-HBV coinfected individuals, such flares may occur after starting antiretroviral therapy.

In a study published in April 1, 2009 issue of Journal of Infectious Diseases, Megan Crane and colleagues assessed the pathogenesis of and risk factors for hepatic flares after the initiation of antiretroviral drugs with dual activity against HIV and HBV. These agents include lamivudine (3TC; Epivir), emtricitabine (Emtriva), and tenofovir (Viread, also in the Truvada and Atripla combination pills).

The investigators looked at hepatic flares in 36 antiretroviral-naive HIV-HBV coinfected patients in Thailand who were beginning HBV-active antiretroviral therapy as part of a prospective clinical trial.

Flares were defined as an ALT level > 5 times the upper limit of normal or > 200 IU/L higher than the baseline level. The researchers also measured activated natural killer (NK) cells and immune biomarkers including interleukin 18 (IL-18), IL-2, IL-6, IL-8, IL-10, soluble CD26 (sCD26), sCD30, sCD8, CXCL-10, CCL-2, tumor necrosis factor-alpha, interferon-gamma, and interferon-alfa.

Results

Overall, 8 participants experienced hepatic flares during follow-up.

Baseline HBV DNA and ALT levels were higher in the 8 patients with flares compared to the 28 patients without flares (P = 0.01).

After initiation of antiretroviral therapy, CXCL-10 levels remained elevated in patients with hepatic flares, but decreased in those without flares (P < 0.01).

sCD30 levels increased and were significantly higher at week 8 in patients with hepatic flares (P < 0.05).

There was a positive correlation between ALT levels and levels of CXCL-10, sCD30, CCL-2, and IL-18 at week 8 (the time of peak ALT), but not at other time points.

"Elevated HBV DNA and ALT levels before the initiation of HBV-active antiretroviral therapy are risk factors for hepatic flares," the study authors concluded.

They added that "The pathogenesis of hepatic flares after the initiation of HBV-active ART is probably consistent with immune restoration disease," also known as immune restoration inflammatory syndrome (IRIS).

Monash University, Melbourne ; Alfred Hospital, Melbourne, ; University of Western Australia, Perth; Royal Perth Hospital and PathWest Laboratory Medicine, Perth; National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, and Vaccine and Cellular Immunology Laboratory, Faculty of Medicine, Chulongkorn University, Bangkok, Thailand.

3/20/09

Reference
M Crane, B Oliver, G Matthews, and others. Immunopathogenesis of Hepatic Flare in HIV/Hepatitis B Virus (HBV)-Coinfected Individuals after the Initiation of HBV-Active Antiretroviral Therapy. Journal of Infectious Diseases 199(7): 974-981. April 1, 2009. (Abstract).