Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin
Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin
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DOI：
10.1111/j.1365-2893.2009.01106.x
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发表时间：
2009-08-01
影响因子：
2.5
通讯作者：
Hayashi, N.
中科院分区：
文献类型：
--
作者：
Hiramatsu, N.;Oze, T.;Hayashi, N.
利巴韦林暴露对病毒学复发的影响在聚乙二醇干扰素（Peg-IFN）和利巴韦林联合治疗慢性丙型肝炎（CH-C）基因型1患者中仍存在争议。本研究旨在调查这一点。984例CH-C基因1型患者入组研究。通过平均实际服用的剂量计算每种药物的药物暴露量。多因素Logistic回归分析显示，肝纤维化程度（P = 0.002）、HCVRNA转阴时间（P <0.001）和利巴韦林平均剂量（P <0.001）与复发显著相关，而聚乙二醇干扰素与复发无关。利巴韦林剂量的逐步减少与复发率从11%到60%的逐步增加有关。对于具有完全早期病毒学应答（c-EVR）的患者（定义为在第12周HCV RNA阴性），在给予利巴韦林≥ 12 mg/kg/天的患者中仅发现4%的复发，并且利巴韦林暴露影响甚至在治疗第12周后的复发，而聚乙二醇干扰素可以在第12周后降低至0.6 μ g/kg/周而不增加复发率。利巴韦林与复发呈剂量依赖关系。在整个治疗期间维持尽可能高的利巴韦林剂量（>= 12 mg/kg/天）可导致对Peg-IFN α-2b加利巴韦林应答的HCV基因型1患者的复发抑制，尤其是在c-EVR患者中。
The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis (P = 0.002), the timing of HCV RNA negativiation (P < 0.001) and the mean doses of ribavirin (P < 0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given >= 12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 mu g/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (>= 12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.