title: Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co-infected patients with advanced immunosuppression.
abstract: OBJECTIVE
  to determine if intrahepatic immune activation is increased in HIV-hepatitis B virus (HBV) co-infected patients compared to HBV mono-infected patients and whether this reduced following HBV-active antiretroviral therapy (ART) in HIV-HBV co-infected patients.
  
  
  METHODS
  : Case-control observational study.
  
  
  METHODS
  we examined liver biopsies for markers of T-cell and monocyte infiltration and activation, natural killer cells, hepatic stellate cell (HSC) activation (staining for alpha smooth muscle actin) and apoptosis [using terminal dUTP nick-end labelling (TUNEL)] in treatment-naive Asian HIV-HBV co-infected (n = 16) and HBV mono-infected patients matched for age and HBV e-antigen status (n = 16). Liver biopsies from a subset of co-infected patients (n = 15) were also compared prior to and following 48 weeks of HBV-active ART.
  
  
  RESULTS
  HIV-HBV co-infected patients had a median CD4 T-cell count of 25 cells/microl and lower alanine aminotransferase levels than HBV mono-infected patients (P = 0.03). In HIV-HBV co-infected patients, hepatocyte apoptosis was increased (P = 0.04) but there were fewer intrahepatic CD4 and CD8 T cells (P < 0.001), lower activation of intrahepatic T cells, Kupffer cells and HSC (P = 0.002, 0.008 and < 0.001, respectively). Following ART, there was a significant decrease in intrahepatic HBsAg staining (P = 0.04) and Kupffer cell activation (P = 0.003).
  
  
  CONCLUSIONS
  we found no evidence of increased intrahepatic mononuclear and HSC activation in this cohort of HIV-HBV co-infected individuals with advanced immune suppression. An increase in intra-hepatic apoptosis in HIV-HBV co-infected individuals may potentially contribute to accelerated fibrosis in this setting.
authors.affiliation: Department of Medicine, University of Melbourne, St. Vincent's Hospital, Melbourne, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Iser
authors.forename: Anchalee
authors.initials: A
authors.lastname: Avihingsanon
authors.forename: Naruemon
authors.initials: N
authors.lastname: Wisedopas
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: Alison
authors.initials: A
authors.lastname: Boyd
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Locarnini
authors.forename: John
authors.initials: J
authors.lastname: Slavin
authors.forename: Paul V
authors.initials: PV
authors.lastname: Desmond
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis / Q000502:physiology*; D004279:DNA, Viral; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D015497:HIV-1 / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000473:pathology* / Q000821:virology; D008297:Male; D016133:Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D004279:DNA, Viral