Pasteur-Cerba, Cergy-Pontoise, France.
Clin Res Hepatol Gastroenterol. 2011 Mar;35(3):204-13. doi: 10.1016/j.clinre.2011.01.005. Epub 2011 Feb 26.
Three gene polymorphisms, interferon-lambda-3 (IL28B), inosinetriphosphatase (ITPA) and bilirubinuridine diphosphate-glucuronosyltransferase (UGT1A1) are associated with treatment (interferon and ribavirin) efficacy and adherence in patients with chronic hepatitis C. The hypothesis was that fibrosis stage estimated with FibroTest instead of biopsy was still an independent predictive factor of sustained virologic response (SVR) when these new polymorphisms were assessed.
Patients receiving standard of care treatment were retrospectively analyzed with determination of IL28B, ITPA, and UGT1A1 polymorphisms. Baseline prognostic factors were combined using logistic regression analysis in a training group (157 patients) and validated in avalidation group (79 patients).
The combination of the five most predictive factors (HCV genotype 2/3, IL28B genotype, FibroTest, ActiTest and viral load) in the training population had AUROC for SVR=0.743 (0.655-0.810; P<0.0001 vs. random), which was validated in the validation population, AUROC=0.753 (0.616-849; P=0.0007 vs. random, not different from training P=0.88). FibroTest remained significant [OR=4.20 (2.59-12.50); P=0.03] after assessment of the IL28B CC, HCV genotype and viral load.
Fibrosis stage assessed by FibroTest is an independent predictor of SVR, after accounting for the IL28B genetic polymorphism. A combination of five baseline biomarkers could simplify the baseline prediction of SVR.
三种基因多态性，干扰素-lambda-3（IL28B）、肌苷三磷酸酶（ITPA）和胆红素尿苷二磷酸葡萄糖醛酸转移酶（UGT1A1）与慢性丙型肝炎患者的治疗（干扰素和利巴韦林）疗效和依从性相关。假设在用 FibroTest 估计纤维化分期而不是进行肝活检时，当评估这些新的多态性时，它仍然是持续病毒学应答（SVR）的独立预测因素。
对接受标准治疗的患者进行回顾性分析，确定 IL28B、ITPA 和 UGT1A1 多态性。使用逻辑回归分析在训练组（157 例患者）中联合确定基线预后因素，并在验证组（79 例患者）中进行验证。
在训练人群中，将五个最具预测性的因素（HCV 基因型 2/3、IL28B 基因型、FibroTest、ActiTest 和病毒载量）组合起来，对 SVR 的 AUROC 为 0.743（0.655-0.810；P<0.0001 与随机对照相比），在验证人群中得到验证，AUROC=0.753（0.616-849；P=0.0007 与随机对照相比，与训练相比无差异，P=0.88）。在评估 IL28B CC、HCV 基因型和病毒载量后，FibroTest 仍然具有统计学意义[OR=4.20（2.59-12.50）；P=0.03]。
在考虑到 IL28B 遗传多态性后，FibroTest 评估的纤维化分期是 SVR 的独立预测因素。五种基线生物标志物的组合可以简化 SVR 的基线预测。
