Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
J Gastroenterol. 2014 Apr;49(4):737-47. doi: 10.1007/s00535-013-0824-z. Epub 2013 May 21.
HCV kinetics during treatment demonstrated strong association with the antiviral outcome of patients treated with pegylated interferon (Peg-IFN) plus ribavirin. However, the relationship between HCV kinetics and pre-treatment factors remains unclear.
Of 547 patients with HCV genotype 1 treated with Peg-IFN alfa-2b plus ribavirin, 401 completed the response-guided therapy and were assessed for per protocol analysis.
The sustained virologic response (SVR) rate was 53 % for all patients, 60 % for those with genotype TT, and 19 % for those with genotype TG/GG according to IL28B (rs8099917) single nucleotide polymorphisms. The SVR rates increased with HCV decrease at week 4; 4 % (2/56) with <1 log10 decrease, 13 % (7/56) with 1-2 log10 decrease, 51 % (44/87) with 2-3 log10 decrease, 64 % (56/87) with 3-4 log10 decrease, 88 % (72/82) with more than 4 log10 decrease but with detectable HCV RNA and 100 % (33/33) with undetectable HCV RNA (p < 0.001). Similarly, SVR rates increased step-by-step in proportion to HCV decrease in both IL28B TT and TG/GG groups, showing almost the same SVR rates for the same conditions. In multivariate analysis, age (p = 0.005) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with SVR. Advanced liver fibrosis (p = 0.004) and the magnitude of HCV decrease at week 4 (p < 0.001) but not IL28B were associated with non-response.
The magnitude of the HCV decrease at week 4 seems to be the most reliable marker for predicting antiviral outcome after starting Peg-IFN plus ribavirin therapy.
聚乙二醇干扰素(Peg-IFN)联合利巴韦林治疗期间的 HCV 动力学与接受治疗的患者的抗病毒疗效密切相关。然而,HCV 动力学与治疗前因素之间的关系尚不清楚。
在 547 例接受 Peg-IFN alfa-2b 联合利巴韦林治疗的 HCV 基因型 1 患者中,有 401 例完成了基于反应的治疗,并进行了方案分析评估。
所有患者的持续病毒学应答(SVR)率为 53%,基因型 TT 患者的 SVR 率为 60%,基因型 TG/GG 患者的 SVR 率为 19%,这是根据 IL28B(rs8099917)单核苷酸多态性确定的。SVR 率随着第 4 周 HCV 的下降而增加;4%(2/56)下降<1log10,13%(7/56)下降 1-2log10,51%(44/87)下降 2-3log10,64%(56/87)下降 3-4log10,88%(72/82)下降>4log10但仍可检测到 HCV RNA,100%(33/33)下降到不可检测的 HCV RNA(p<0.001)。同样,在 IL28B TT 和 TG/GG 组中,SVR 率也随着 HCV 的下降而逐步增加,在相同条件下显示出几乎相同的 SVR 率。多变量分析显示,年龄(p=0.005)和第 4 周 HCV 下降幅度(p<0.001),而不是 IL28B,与 SVR 相关。晚期肝纤维化(p=0.004)和第 4 周 HCV 下降幅度(p<0.001),而不是 IL28B,与无应答相关。
第 4 周 HCV 下降幅度似乎是预测 Peg-IFN 联合利巴韦林治疗开始后抗病毒疗效的最可靠标志物。