title: Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)-coinfected individuals after the initiation of HBV-active antiretroviral therapy.
abstract: 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.
authors.affiliation: Department of Medicine, Monash University, and Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Crane
authors.forename: Ben
authors.initials: B
authors.lastname: Oliver
authors.forename: Gail
authors.initials: G
authors.lastname: Matthews
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Sasiwimol
authors.initials: S
authors.lastname: Ubolyam
authors.forename: Vesna
authors.initials: V
authors.lastname: Markovska
authors.forename: J Judy
authors.initials: JJ
authors.lastname: Chang
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
authors.forename: Kumar
authors.initials: K
authors.lastname: Visvanathan
authors.forename: Martyn
authors.initials: M
authors.lastname: French
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: 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
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D000410:Alanine Transaminase