Hepatic inflammatory cytokine mRNA expression in hepatitis C virus–human immunodeficiency virus co‐infection

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Abstract
Summary.  Although epidemiologic studies have documented that hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co‐infected patients have accelerated fibrogenesis, especially those with CD4+ cell counts 3, the pathogenic mechanisms are poorly understood. We investigated whether severe immunodeficiency in co‐infection is associated with changes in intrahepatic inflammatory cytokine mRNA levels. We measured interferon (IFN)‐γ, tumour necrosis factor‐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 samples from HCV mono‐infected (n = 19) and HCV/HIV co‐infected (n = 24) patients. Co‐infected patients had decreased intrahepatic mRNA levels of IFN‐γ (P = 0.09), IL‐4 (P = 0.05) and IL‐12p35 (P = 0.04) compared with mono‐infected patients, while IL‐10 was increased (P = 0.07). In co‐infected patients, IFN‐γ mRNA levels increased linearly with increasing peripheral CD4+ cell counts by 1.23 times relative to the calibrator for every 100 CD4+ cells/mm3 increase (P = 0.02). No other cytokines were significantly associated with CD4+ cell counts. In conclusion, HIV‐induced lymphopenia may result in hepatic inflammatory cytokine suppression in HCV/HIV co‐infection. Intrahepatic IFN‐γ levels are significantly reduced in patients with advanced immunodeficiency. Further studies are needed to assess whether decreased IFN‐γ secretion by HCV‐specific CD4+ cells may account for accelerated fibrogenesis in these patients.