Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
J Infect Dis. 2011 Jun 1;203(11):1629-36. doi: 10.1093/infdis/jir113.
Single-nucleotide polymorphisms (SNPs) near the IL28B gene have recently been associated with spontaneous hepatitis C virus (HCV) clearance and response to interferon-based therapies in patients with chronic hepatitis C. Because human immunodeficiency virus (HIV) coinfection appears to accelerate HCV-related liver fibrosis progression, any influence of IL28B SNP on the risk of developing cirrhosis might be more easily recognized in the coinfected population.
All HIV-HCV-coinfected patients who underwent hepatic elastography before initiating a course of pegylated interferon plus ribavirin therapy at 2 Spanish clinics were retrospectively identified. Liver cirrhosis was defined as >14.5 kPa by transient elastography. The IL28B rs12979860 SNP was examined in a blinded fashion.
A total of 304 HIV-HCV-coinfected individuals were analyzed (mean age, 43 years; 80% were male; and 85% were receiving antiretroviral therapy), of whom 18% had cirrhosis. IL28B genotype distribution was as follows: CC, 46%; CT, 43%; and TT, 11%. Cirrhosis was more frequent in CC than CT/TT carriers (24% vs 13%; P = .01). Logistic regression analysis revealed that older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.99-1.12]; P = .08), past alcohol abuse (OR, 1.97; 95% CI, 0.95-4.06; P = .07), and CC IL28B genotype (OR, 2.32; 95% CI, 1.22-4.41; P = .01) were predictors of cirrhosis. Interestingly, mean (SD) alanine aminotransferase (ALT) levels were greater (90 ± 53 vs 71 ± 33 IU/L;, P = .01) in IL28B CC than CT/TT carriers during the prior 4.8 ± 3.8 years.
The IL28B rs12979860 CC genotype is associated with a higher prevalence of cirrhosis in HIV-HCV-coinfected patients than CT/TT genotypes, suggesting that IL28B CC carriers may experience a more rapid progression of HCV-related liver fibrosis, perhaps as result of increased liver inflammation. Thus, access to HCV treatment is of utmost importance in IL28B CC carriers, in whom treatment response is better and in whom progression to cirrhosis might occur more rapidly.
最近发现白细胞介素 28B（IL28B）基因附近的单核苷酸多态性（SNP）与慢性丙型肝炎（HCV）患者的自发性 HCV 清除和干扰素为基础的治疗反应有关。由于人类免疫缺陷病毒（HIV）合并感染似乎会加速 HCV 相关肝纤维化的进展，因此在合并感染人群中，IL28B SNP 对发生肝硬化的风险的任何影响可能更容易被识别。
我们回顾性地确定了在西班牙的 2 家诊所接受聚乙二醇干扰素加利巴韦林治疗前接受瞬时弹性成像的所有 HIV-HCV 合并感染患者。通过瞬时弹性成像，肝纤维化定义为>14.5kPa。以盲法检测 IL28B rs12979860 SNP。
共分析了 304 例 HIV-HCV 合并感染患者（平均年龄 43 岁；80%为男性；85%正在接受抗逆转录病毒治疗），其中 18%患有肝硬化。IL28B 基因型分布如下：CC，46%；CT，43%；TT，11%。CC 携带者比 CT/TT 携带者更易发生肝硬化（24%比 13%；P=0.01）。logistic 回归分析显示，年龄较大（比值比[OR]，1.05；95%置信区间[CI]，0.99-1.12；P=0.08）、既往酒精滥用（OR，1.97；95%CI，0.95-4.06；P=0.07）和 CC IL28B 基因型（OR，2.32；95%CI，1.22-4.41；P=0.01）是肝硬化的预测因素。有趣的是，在过去的 4.8±3.8 年中，IL28B CC 携带者的丙氨酸氨基转移酶（ALT）水平更高（90±53 vs 71±33IU/L，P=0.01）。
IL28B rs12979860 CC 基因型与 HIV-HCV 合并感染患者中肝硬化的更高患病率相关，与 CT/TT 基因型相比，这表明 IL28B CC 携带者可能经历更快速的 HCV 相关肝纤维化进展，可能是由于肝脏炎症增加所致。因此，HCV 治疗对 IL28B CC 携带者至关重要，因为他们的治疗反应更好，而且可能更快进展为肝硬化。
