title: 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.
abstract: 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.
authors.affiliation: Department of Experimental and Clinical Medical Sciences, Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Fabris
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Annarosa
authors.initials: A
authors.lastname: Cussigh
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fontanini
authors.forename: Cosimo
authors.initials: C
authors.lastname: Colletta
authors.forename: Carmen
authors.initials: C
authors.lastname: Vandelli
authors.forename: Sara
authors.initials: S
authors.lastname: Cmet
authors.forename: Elisa
authors.initials: E
authors.lastname: Ceriani
authors.forename: Carlo
authors.initials: C
authors.lastname: Smirne
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002784:Cholesterol / Q000097:blood*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D000637:Transaminases / Q000097:blood; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D002784:Cholesterol; D007372:Interferons; D007378:Interleukins; D000637:Transaminases; C000624353:interferon-lambda, human; D000095022:Interferon Lambda