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Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus–related chronic hepatitis: Insulin resistance and response to antiviral therapy
Author(s) -
Persico Marcello,
Capasso Mario,
Persico Eliana,
Svelto Monica,
Russo Roberta,
Spano Daniela,
Crocè Lori,
La Mura Vincenzo,
Moschella Francesco,
Masutti Flora,
Torella Roberto,
Tiribelli Claudio,
Iolascon Achille
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21782
Subject(s) - socs3 , ribavirin , genotype , hepatitis c virus , immunology , pegylated interferon , medicine , hepatitis c , hepacivirus , virology , virus , biology , gastroenterology , gene , cancer , genetics , suppressor
The response to antiviral therapy is lower in hepatitis C virus (HCV) patients with genotype 1 than in those with genotype 2. Overexpression of the suppressor of cytokine signaling 3 (SOCS3) gene in liver tissue is associated with a poorer treatment outcome in patients with chronic hepatitis C viral genotype 1. Also, insulin resistance has been implicated in nonresponse to an anti‐HCV treatment. To understand why HCV genotype 1 patients respond differently, we investigated SOCS3 gene expression, metabolic syndrome (MS), and the response to therapy in a cohort of patients with HCV‐related hepatitis. A total of 198 patients (108 with genotype 1 and 90 with genotype 2) treated with pegylated interferon plus ribavirin were consecutively enrolled in the study. We measured SOCS3 expression in Epstein‐Barr virus–transformed lymphoblastoid cell lines derived from peripheral lymphocytes of a subset of 130 patients. MS was more frequent in genotype 1 patients than in genotype 2 patients ( P < 0.01). Nonresponders ( P < 0.01), MS ( P < 0.001), and genotype 1 ( P < 0.001) were significantly related to SOCS3 overexpression. However, SOCS3 levels were higher in nonresponders also, regardless of the genotype ( P < 0.01). In a univariate analysis, the genotype ( P < 0.001), age ( P < 0.001), SOCS3 ( P < 0.001), and MS ( P < 0.001) were significantly related to the response to therapy. However, in a multivariate analysis, SOCS3 was the only independent predictor of the response (odds ratio = 6.7; P < 0.005). Conclusion: We speculate that SOCS3 expression per se may influence the response to antiviral therapy and that the genotype 1b virus might induce its up‐regulation. This may account for the different responses to therapy between genotype 1–infected and genotype 2–infected patients. (H EPATOLOGY 2007.)