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Endogenous levels of mRNA for IFNs and IFN‐related genes in hepatic biopsies of chronic HCV‐infected and non‐alcoholic steatohepatitis patients
Author(s) -
Abbate Isabella,
Romano Mario,
Longo Roberta,
Cappiello Giuseppina,
Lo Iacono Oreste,
Di Marco Vito,
Paparella Concetta,
Spanǒ Alberto,
Capobianchi Maria Rosaria
Publication year - 2003
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.10433
Subject(s) - steatohepatitis , interferon , viral load , immunology , interferon gamma , biology , alcoholic liver disease , medicine , fatty liver , virus , cytokine , disease , cirrhosis
To investigate the intra‐hepatic activation of the IFN system in patients affected by chronic HCV‐infection in comparison with that observed in a non‐infectious liver disease such as non‐alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon‐α, interferon‐β and interferon‐γ as well as of IFN‐related genes (IFNAR‐1, STAT1α, PKR, 2‐5 AS, IRF‐1, ICE and IL‐18). In HCV‐infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty‐four chronic untreated HCV‐infected subjects and seven patients with non‐alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra‐hepatic mRNA levels of IFNs and related genes were assessed by semi‐quantitative RT‐PCR. In comparison with non‐alcoholic steatohepatitis, in HCV‐infected subjects IFN‐α and ‐β mRNA levels were significantly lower, whereas IFN‐γ, IFNAR‐1, STAT1α IRF‐1, and IL‐18 mRNA were upregulated. Moreover, IFN‐γ mRNA steady state levels were correlated positively with those of IFNAR‐1, IRF‐1, and IL‐18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL‐18‐specific mRNA, viral load was not related to liver injury. IFN‐γ and IRF‐1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN‐α and ‐β mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN‐γ system and a downregulated IFN‐α and ‐β system, probably due to a mixed effect exerted by HCV‐specific and inflammatory non‐specific factors. J. Med. Virol. 70:581–587, 2003. © 2003 Wiley‐Liss, Inc.