Istituto Nazionale Genetica Molecolare, Milano, Italy.
Hepatology. 2011 Oct;54(4):1127-34. doi: 10.1002/hep.24503. Epub 2011 Aug 19.
Polymorphisms in the interleukin-28B (IL28B) region are associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Nevertheless, it is unknown whether genetic variation at the IL28B locus influences the natural history of chronic HCV infection. Thus, we asked whether an association between IL28B polymorphisms and liver fibrosis progression existed. We studied 247 consecutive patients with chronic HCV, an accurate estimate of the date of infection, and a liver biopsy performed before any treatment. No patient had a history of alcohol abuse or coinfection with other viruses. We assessed the role of rs8099917 and rs12979860 polymorphisms and the effect of host and environmental factors on fibrosis progression. Blood transfusion (75%) was the main modality of infection. Median age at infection was 21 years, and median interval between infection and liver biopsy was 25 years. One hundred twenty-nine patients (52%) were infected by HCV-1, 74 (30%) by HCV-2, 34 (14%) by HCV-3, and 10 (4%) by HCV-4. Bridging fibrosis/cirrhosis (Ishak ≥ 4) was detected in 24% of patients. Age at infection had a marked effect on fibrosis progression by both a linear model and Cox proportional-hazard regression (P < 2E-16). A 12.1% increase in the hazard of advanced fibrosis was estimated for each additional year at infection, suggesting that this was the major explanatory variable in this cohort. Male gender (P < 0.05), HCV genotype 3 (P < 0.001) and steatosis (P < 0.05) were also associated with faster fibrosis progression. Conversely, the two IL28B polymorphisms had no impact on fibrosis progression.
In HCV patients with a known date of infection, IL28B genotype was not associated with fibrosis progression rate or with the risk of developing advanced liver fibrosis.
白细胞介素 28B（IL28B）区域的多态性与丙型肝炎病毒（HCV）感染中的自发性和治疗诱导的病毒清除有关。然而，尚不清楚 IL28B 基因座的遗传变异是否会影响慢性 HCV 感染的自然史。因此，我们询问了 IL28B 多态性与肝纤维化进展之间是否存在关联。我们研究了 247 例连续的慢性 HCV 患者，这些患者具有准确的感染日期，并且在任何治疗之前都进行了肝活检。没有患者有酗酒史或合并感染其他病毒。我们评估了 rs8099917 和 rs12979860 多态性的作用以及宿主和环境因素对纤维化进展的影响。输血（75%）是主要的感染方式。感染时的中位年龄为 21 岁，感染与肝活检之间的中位间隔为 25 年。129 例（52%）患者感染 HCV-1，74 例（30%）感染 HCV-2，34 例（14%）感染 HCV-3，10 例（4%）感染 HCV-4。24%的患者检测到桥接纤维化/肝硬化（Ishak≥4）。线性模型和 Cox 比例风险回归均显示，感染时的年龄对纤维化进展有显著影响（P<2E-16）。感染每增加一年，发生晚期纤维化的风险估计增加 12.1%，这表明这是该队列中的主要解释变量。男性（P<0.05）、HCV 基因型 3（P<0.001）和脂肪变性（P<0.05）也与纤维化进展较快相关。相反，两种 IL28B 多态性与纤维化进展无关。
在具有已知感染日期的 HCV 患者中，IL28B 基因型与纤维化进展率或发生晚期肝纤维化的风险无关。
