title: Serum concentration of gammaGT is a surrogate marker of hepatic TNF-alpha mRNA expression in chronic hepatitis C.
abstract: Serum gammaGT levels and hepatic expression of tumor necrosis factor-alpha (TNF-alpha) are host factors that can independently predict the outcome of interferon (IFN) treatment in patients with chronic hepatitis C virus (HCV) infection. To explore whether a correlation exists between these two factors, we measured pretreatment gammaGT levels in serum and TNF-alpha mRNA levels in liver biopsies of chronic HCV patients. Seventy-two HCV patients treated with 3-to-5 million units of IFN-alpha three times a week were enrolled in the study. Treatment lasted 24 weeks and was followed by a 48-week follow-up period. Efficacy was assessed by measuring HCV RNA and alanine aminotransferase by the end of follow-up. Twelve patients (16.6%) showed a sustained biochemical and virological response. Normal pretreatment gammaGT levels, low HCV RNA titer, and infection with genotype other than HCV-1 were shown to be independent predictors of sustained response. Hepatic levels of TNF-alpha mRNA, quantified by polymerase chain reaction, were significantly higher in nonresponders (3.44 arbitrary units) compared to sustained responders (1.84 arbitrary units; P = 0.009). Values </=3.12 arbitrary units independently predicted a sustained response to IFN (P = 0.014). Finally, TNF-alpha mRNA levels were significantly correlated with serum gammaGT levels (r = 0.79, P < 0.0001). These findings suggest that serum gammaGT levels may represent a surrogate marker of hepatic TNF-alpha expression, thus explaining the importance of serum gammaGT levels in predicting treatment outcome.
authors.affiliation: DISP LITA Vialba, University of Milan, 20157, Milan, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Taliani
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Badolato
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nigro
authors.forename: Mara
authors.initials: M
authors.lastname: Biasin
authors.forename: Vieri
authors.initials: V
authors.lastname: Boddi
authors.forename: Caterina
authors.initials: C
authors.lastname: Pasquazzi
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005723:gamma-Glutamyltransferase