Division of Gastroenterology, Dipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, Italy.
Clin Gastroenterol Hepatol. 2013 Mar;11(3):311-7.e1. doi: 10.1016/j.cgh.2012.11.022. Epub 2012 Dec 4.
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.
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.
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.
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.
基因型 1 慢性丙型肝炎（G1 CHC）患者常因代谢和病毒因素而发生脂肪变性和胰岛素抵抗（IR）。这些因素加速了肝病的进展，并降低了对治疗的反应。G1 CHC 患者对治疗的持续病毒学应答（SVR）与白细胞介素 28B（IL28B）基因附近的多态性密切相关，但 IL28B 基因型与 IR 之间的相互作用及其对 SVR 的综合影响尚未确定。我们检测了 IL28B rs12979860 单核苷酸多态性与代谢特征（包括 IR）之间的关联，并评估了它们对 SVR 的影响。
我们对来自 3 个三级中心的 434 名白人 G1 CHC 患者进行了 IL28B rs12979860 的基因分型分析。代谢谱分析包括通过稳态模型评估评估血脂水平和 IR。
IL28B 中的 CC 多态性患者的总胆固醇和低密度脂蛋白胆固醇水平较高，甘油三酯水平较低，IR 和中重度脂肪变性的发生率较低（P <.05）。通过多变量逻辑回归分析，体重指数（比值比[OR]，1.223；P <.001）、甘油三酯水平（OR，1.007；P =.006）、IL28B 的 CC 多态性（OR，0.378；P =.001）和大于 850,000 IU/mL 的 HCV RNA 水平（OR，1.803；P =.01）与 IR 相关。IL28B 的 CC 多态性（OR，8.350；P <.001）和 IR（OR，0.432；P =.005），而不是脂肪变性（OR，0.582；P =.25）与 SVR 相关。
在白人 G1 CHC 患者中，IL28B rs12979860 CC 基因型与 IR 降低有关。IL28B rs12979860 基因型和稳态模型评估的 IR 强烈影响抗病毒治疗的结果。
