Article

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

Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
AIDS (London, England) (Impact Factor: 6.56). 02/2008; 22(2):203-10. DOI: 10.1097/QAD.0b013e3282f3553b
Source: PubMed

ABSTRACT 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.
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.
Despite their well preserved peripheral blood CD4 cell counts (median 598 cells/microl), HIV/HCV-co-infected patients displayed significantly lower CD4 mRNA levels than HCV-mono-infected patients, whereas increased mRNA levels of CD3epsilon, TCRalpha, CD8alpha and CD8beta suggested intrahepatic enrichment of CD8 T cells in HIV co-infection. Intrahepatic mRNA levels of the inflammatory cytokines interferon gamma (IFN-gamma), 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.
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.

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    • "Gonzalez et al. assessed cytokine levels in liver biopsies on liver samples from HCV/HIV co-infected and HCV mono-infected patients. They measured IFN-γ, Tumor Necrosis Factor (TNF)-α, Transforming Growth Factor (TGF)-β1, interleukin (IL)-4, IL-10, IL-12p35 and IL-12p40 mRNA levels by real-time PCR performed on liver biopsies of HCV mono-infected (n=19) and HCV/HIV co-infected (n=24) patients (Table 1).59-67 The results showed that the co-infected patients had decreased intrahepatic mRNA levels of IFN-γ, IL-4 and IL-12p35 compared with mono-infected patients while IL-10 was increased. "
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