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.


CONCLUSIONS
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.
Crane
Megan
M
Department of Medicine, Monash University, and Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia.
Oliver
Ben
B
Matthews
Gail
G
Avihingsanon
Anchalee
A
Ubolyam
Sasiwimol
S
Markovska
Vesna
V
Chang
J Judy
JJ
Dore
Gregory J
GJ
Price
Patricia
P
Visvanathan
Kumar
K
French
Martyn
M
Ruxrungtham
Kiat
K
Lewin
Sharon R
SR
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D006509:Hepatitis B / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D007694:Killer Cells, Natural / Q000276:immunology; D012307:Risk Factors
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D000410:Alanine Transaminase