title: Naive HIV/HCV-coinfected patients have higher intrahepatic pro-inflammatory cytokines than coinfected patients treated with antiretroviral therapy.
abstract: In the era of antiretroviral therapy, liver disease has emerged as an important cause of morbidity and mortality in HIV/hepatitis C virus (HCV) coinfected patients. It is believed that HCV is a non-cytopathic virus and that T-cell-mediated events (including the production of pro-inflammatory cytokines) have an important role in promoting both liver damage and viral clearance. Whether HIV coinfection or antiretroviral therapies influence such events is still unclear. In the current study, we compared the expression of NKp46 (a natural killer cell marker), CD3 (a T-cell marker), interferon-gamma (IFN-gamma), tumour-necrosis factor-alpha (TNF-alpha; pro-inflammatory cytokines) and interleukin-10 (IL-10; an anti-inflammatory cytokine) mRNA in the liver of naive HIV/HCV-coinfected patients (group one, n=14), coinfected patients treated with antiretroviral therapy (group two, n=23) and naive HCV mono-infected patients (group three, n=24). All three groups had comparable HCV viremia, with coinfected patients showing similar and relatively high CD4+ T-cell counts and significantly different HIV vireamia. Interestingly, when compared to groups two and three, group one showed significantly higher intrahepatic mRNA levels for CD3, IFN-gamma and TNF-alpha, whereas the expression of NKp46 and IL-10 were comparable in all three groups. Further, higher histopathological grading scores within each group were independently associated with higher mRNA contents for CD3 and IFN-gamma and higher serum alanine aminotransferase levels at the time of liver biopsy. Together, these results suggest that HIV infection may exacerbate the immune-mediated inflammatory response in the liver of patients chronically infected with HCV and antiretroviral therapy may prevent this effect.
authors.affiliation: Infectious Disease Department, San Raffaele Scientific Institute, Milan, Italy. sitia.giovanni@hsr.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sitia
authors.forename: Anna
authors.initials: A
authors.lastname: De Bona
authors.forename: Sabrina
authors.initials: S
authors.lastname: Bagaglio
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.forename: Carlo T
authors.initials: CT
authors.lastname: Paties
authors.forename: Caterina
authors.initials: C
authors.lastname: Uberti-Foppa
authors.forename: Luca G
authors.initials: LG
authors.lastname: Guidotti
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Giulia
authors.initials: G
authors.lastname: Morsica
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D017252:CD3 Complex / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000821:virology; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D017252:CD3 Complex; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma