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The interleukin 28B rs12979860 C/T polymorphism and serum cholesterol as predictors of fibrosis progression in patients with chronic hepatitis C and persistently normal transaminases
Author(s) -
Fabris Carlo,
Falleti Edmondo,
Cussigh Annarosa,
Bitetto Davide,
Fontanini Elisabetta,
Colletta Cosimo,
Vandelli Carmen,
Cmet Sara,
Ceriani Elisa,
Smirne Carlo,
Toniutto Pierluigi,
Pirisi Mario
Publication year - 2012
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.23259
Subject(s) - medicine , gastroenterology , interleukin 28b , genotype , hepatitis c , cohort , cholesterol , hepatitis c virus , immunology , virus , ribavirin , biology , gene , biochemistry
The interleukin 28B ( IL‐28B ) rs12979860 C/T polymorphism is a predictor of spontaneous and treatment‐induced hepatitis C virus (HCV) clearance. The C/C genotype is associated with higher serum cholesterol, predictor of a favorable outcome in chronic hepatitis C. Whether IL‐28B polymorphism and serum cholesterol play a role in modulating the history of mild hepatitis C is unknown. To clarify this issue, 93 untreated patients infected with HCV with normal or near‐normal transaminases and an initial Ishak staging score ≤1 were investigated retrospectively in the longitudinal study (median histological follow‐up of 10 years). An additional confirmatory cohort of 143 patients with chronic HCV infection and abnormal levels of transaminases was evaluated in the cross‐sectional study. In the longitudinal study, at the end of follow‐up, Ishak staging scores progressed more frequently among carriers of a T/* allele who had a baseline serum cholesterol ≤175 mg/dl than in remaining patients: 6/36 (change ≤0), 15/45 (change 1–2), 6/12 (change ≥3), improvement chi‐square P < 0.02, OR 3.1, 95% C.I. 1.3–7.7. In the cross‐sectional study, the frequency of patients carrying the T/T genotype or serum cholesterol values ≤175 mg/dl increased starting from those with a staging score ≤2 (36/76, 47.4%), to those with a staging score of 3–4 (26/41, 63.4%) and to those with a staging score of 5–6 (20/26, 76.9%, P < 0.01 for linear trend). In conclusion, the interaction between IL‐28B rs12979860 T/T genotype and low serum cholesterol concentration is an independent predictor of a worse disease course among patients infected with HCV with normal or near‐normal transaminases. J. Med. Virol. 84:747–755, 2012. © 2012 Wiley Periodicals, Inc.