Intrahepatic mRNA expression in hepatitis C virus and HIV/hepatitis C virus co-infection: Infiltrating cells, cytokines, and influence of HAART

Thomas Kuntzen, Cristina Tural, Bin Li, Georg Feldmann, Bernd Kupfer, Hans Dieter Nischalke, Bonaventura Clotet, Tilman Sauerbruch, Juergen K. Rockstroh, Ulrich Spengler

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32 Citations (Scopus)

Abstract

OBJECTIVE: Liver disease is more progressive in HIV/hepatitis C virus (HCV) co-infection than in HCV infection alone. This accelerated pathogenesis is probably influenced by differences in the composition of infiltrating inflammatory cells and the local release of inflammatory and profibrogenic cytokines. METHODS: Using quantitative real-time reverse transcriptase- polymerase chain reaction (qRT-PCR) we studied intrahepatic messenger RNA levels of cytokines and cellular markers defining distinct subsets of inflammatory cells in liver biopsies from 33 HCV-mono-infected and 40 HIV/HCV-co-infected patients. RESULTS: Despite their well preserved peripheral blood CD4 cell counts (median 598 cells/μl), HIV/HCV-co-infected patients displayed significantly lower CD4 mRNA levels than HCV-mono-infected patients, whereas increased mRNA levels of CD3ϵ, TCRα, CD8α and CD8β suggested intrahepatic enrichment of CD8 T cells in HIV co-infection. Intrahepatic mRNA levels of the inflammatory cytokines interferon gamma (IFN-γ), regulated upon activation, normal T-cell expressed and secreted (RANTES, CCL5), macrophage inflammatory protein 1 alpha (CCL3) and interferon-inducible protein 10 (CXCL10) were significantly higher in HIV-positive than in HIV-negative patients, whereas mRNA levels of the profibrogenic cytokines macrophage chemoattractant protein 1 (CCL2), secondary lymphochemokine (CCL21) and stroma-derived factor 1 (CXCL12) did not differ between the two groups. All changes were less pronounced in the subgroup of HIV-positive patients receiving antiretroviral treatment (HAART) than in untreated HIV-positive patients. CONCLUSION: The accelerated liver disease observed in HIV/HCV-co-infected patients might reflect enhanced intrahepatic inflammatory responses rather than increased local transcription of directly profibrogenic cytokines. © 2008 Lippincott Williams & Wilkins, Inc.
Original languageEnglish
Pages (from-to)203-210
JournalAIDS
Volume22
Issue number2
DOIs
Publication statusPublished - 1 Jan 2008

Keywords

  • Interferon gamma
  • Interferon-inducible protein 10
  • Macrophage chemoattractant protein 1
  • Macrophage inflammatory protein 1 alpha
  • Regulated upon activation: normal T-cell expressed and secreted
  • Secondary lymphochemokine
  • Stroma-derived factor 1

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