Effects of IL28B rs12979860 CC Genotype on Metabolic Profile and Sustained Virologic Response in Patients With Genotype 1 Chronic Hepatitis C

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• 作者：Salvatore Petta^? ; ^{petsa@inwind.it} ; Chiara Rosso^&Dagger ; ; Reynold Leung^§ ; ; Maria Lorena Abate^&Dagger ; ; David Booth^§ ; ; Federico Salomone^&Dagger ; ; Roberto Gambino^¡Î ; Mario Rizzetto^&Dagger ; ; Paolo Caviglia^&Dagger ; ; Antonina Smedile^&Dagger ; ; Stefania Grimaudo^? ; Calogero Camm&agrave ; ^? ; Antonio Craxì ; ^? ; Jacob George^§ ; ; Elisabetta Bugianesi^&Dagger ;
• 关键词：LDL ; HCV Infection ; Cirrhosis ; Drug Response
• 刊名：Clinical Gastroenterology and Hepatology
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：11
• 期：3
• 页码：311-317.e1
• 全文大小：585 K

文摘

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Background & Aims

Patients with genotype 1 chronic hepatitis C (G1 CHC) frequently develop steatosis and insulin resistance (IR), caused by metabolic and viral factors. These accelerate the progression of liver disease and reduce the response to therapy. A sustained virologic response (SVR) to therapy in patients with G1 CHC is associated strongly with polymorphisms near the interleukin-28B (IL28B) gene, but the interaction between IL28B genotype and IR, and their combined effects on SVR, have not been defined. We tested the association between the IL28B rs12979860 single-nucleotide polymorphism and metabolic features, including IR, and evaluated their effects on SVR.

Methods

We performed genotype analysis of IL28B rs12979860 for 434 white G1 CHC patients who underwent consecutive biopsy analysis at 3 tertiary centers. Metabolic profile analyses included assessments of lipid levels and IR by the homeostasis model assessment.

Results

Patients with the CC polymorphism in IL28B had higher levels of total and low-density lipoprotein cholesterol, lower levels of triglycerides, and a lower prevalence of IR and moderate-severe steatosis (P < .05) than patients without this genotype. By multiple logistic regression analysis, body mass index (odds ratio [OR], 1.223; P < .001), level of triglycerides (OR, 1.007; P = .006), the CC polymorphism in IL28B (OR, 0.378; P = .001), and levels of HCV RNA greater than 850,000 IU/mL (OR, 1.803; P = .01) were associated with IR. The CC polymorphism in IL28B (OR, 8.350; P < .001) and IR (OR, 0.432; P = .005), but not steatosis (OR, 0.582; P = 0.25), was associated with an SVR.

Conclusions

In white patients with G1 CHC, the IL28B rs12979860 CC genotype is associated with reduced IR. IL28B rs12979860 genotype and IR by the homeostasis model assessment strongly affect the outcome of antiviral therapy.