Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
J Viral Hepat. 2014 Oct;21(10):e118-28. doi: 10.1111/jvh.12246. Epub 2014 Mar 12.
The success of current antiviral treatment for hepatitis C virus (HCV) recurrence in liver transplant (LT) recipients remains limited. We aimed at evaluating the value of IL28B genotype and early viral kinetics to predict response to standard treatment in the transplant setting. We retrospectively evaluated 104 LT recipients treated for HCV genotype 1 recurrence between 2001 and 2010. Baseline variables, including IL28B genotype, and early viral kinetics were compared among patients who did or did not achieve a sustained virological response (SVR). Logistic regression analyses of candidate variables were conducted to generate a reliable predictive model based on the minimum set of variables. Twenty-nine (28%) achieved an SVR. On multivariate analysis, the magnitude of HCV RNA decline at 4 weeks (OR: 3.74, 95% CI: 1.64-9.39; P = 0.003) and treatment compliance (OR: 35.27, 95% CI: 3.35-365.54; P = 0.003) were the only independent predictors of SVR. Favourable recipient IL28B genotype significantly correlates with virological response at week 4 (OR 3.23; 95% CI, 1.12-9.15; P = 0.03). By logistic regression analysis, a model including donor age, recipient rs12979860 genotype and viral load at 4 weeks showed the best predictive value for SVR with an area under the receiver operating curve of 0.861. Favourable recipient IL28B genotype strongly correlates with the viral response at week 4 which is the strongest predictor of response. The combination of recipient IL28B genotype and donor age with the week 4 response reliably estimates the probability of SVR early on-treatment and may facilitate therapeutic strategies incorporating new antiviral agents.
目前，对于肝移植（LT）受者丙型肝炎病毒（HCV）复发的抗病毒治疗效果仍然有限。我们旨在评估 IL28B 基因型和早期病毒动力学在移植环境中预测标准治疗反应的价值。我们回顾性评估了 2001 年至 2010 年间接受 HCV 基因型 1 复发治疗的 104 例 LT 受者。比较了未达到持续病毒学应答（SVR）和达到 SVR 的患者之间的基线变量，包括 IL28B 基因型和早期病毒动力学。对候选变量进行逻辑回归分析，以根据最小变量集生成可靠的预测模型。29 例（28%）达到 SVR。多变量分析显示，4 周时 HCV RNA 下降幅度（OR：3.74，95%CI：1.64-9.39；P = 0.003）和治疗依从性（OR：35.27，95%CI：3.35-365.54；P = 0.003）是 SVR 的唯一独立预测因子。有利的受者 IL28B 基因型与第 4 周时的病毒学反应显著相关（OR 3.23；95%CI，1.12-9.15；P = 0.03）。通过逻辑回归分析，包括供体年龄、受者 rs12979860 基因型和第 4 周时病毒载量的模型显示出对 SVR 的最佳预测价值，ROC 曲线下面积为 0.861。有利的受者 IL28B 基因型与第 4 周时的病毒反应密切相关，是反应的最强预测因子。受者 IL28B 基因型与供体年龄和第 4 周反应的结合可早期可靠地估计 SVR 的概率，并可能促进包含新型抗病毒药物的治疗策略。
