Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co-infected patients with advanced immunosuppression

David M. Iser, Anchalee Avihingsanon, Naruemon Wisedopas, Alexander J. Thompson, Alison Boyd, Gail V. Matthews, Stephen A. Locarnini, John Slavin, Paul V. Desmond, Sharon R. Lewin

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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. Design: 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/μl 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.

Original languageEnglish
Pages (from-to)197-205
Number of pages9
JournalAIDS
Volume25
Issue number2
DOIs
StatePublished - 14 Jan 2011
Externally publishedYes

Keywords

  • HIV
  • apoptosis
  • hepatitis B virus
  • immunohistochemistry
  • liver

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