Flares in HIV-HBV Coinfected Patients after Starting Antiretroviral Therapy
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
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
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.
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.
HBV DNA and ALT levels before the initiation of HBV-active antiretroviral therapy
are risk factors for hepatic flares," the study authors concluded.
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).
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.
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).