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肾功能不全对慢性丙型肝炎病毒感染患者中利巴韦林与全口服直接抗病毒药物联合方案的剂量降低及病毒学疗效的影响

Influence of renal dysfunction on dose reduction and virologic efficacy of regimens combining ribavirin and all-oral direct acting antivirals in patients with chronic hepatitis C virus infection.

作者信息

Nakashima Megumi, Toyoda Hidenori, Tada Toshifumi, Mizuno Kazuyuki, Iio Etsuko, Tanaka Yasuhito, Sugiyama Tadashi, Yoshimura Tomoaki, Kumada Takashi

机构信息

Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Japan.

Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.

出版信息

Hepatol Res. 2019 May;49(5):512-520. doi: 10.1111/hepr.13311. Epub 2019 Feb 7.

DOI:10.1111/hepr.13311
PMID:30628746
Abstract

AIM

Several interferon (IFN)-free, all-oral regimens with direct acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection also include ribavirin (RBV). We investigated the influence of renal dysfunction on virologic efficacy and adverse effects in 189 patients with HCV genotype 2 infection who received combination RBV-DAA regimens.

METHODS

The incidence of RBV-induced anemia, RBV dose reduction, and virologic efficacy were compared according to baseline renal function as defined by the estimated glomerular filtration rate (eGFR).

RESULTS

Patients with renal dysfunction (eGFR = 30-59 mL/min/1.73 m ) had higher rate of RBV dose reduction and more marked decreases in hemoglobin levels. These findings were more pronounced in patients with the ITPA CC genotype, who are more sensitive to RBV-induced anemia. Although there were no statistically significant differences in sustained virologic response (SVR) rates according to renal function overall (P = 0.1650), the SVR rate was significantly lower in patients who required RBV dose reduction than in those who did not (P < 0.0001).

CONCLUSIONS

Baseline renal dysfunction could unfavorably affect the outcomes of RBV-DAA in patients with chronic HCV infection due to the increased risk of RBV dose reduction, even in the era of IFN-free DAA regimens.

摘要

目的

几种用于慢性丙型肝炎病毒(HCV)感染的不含干扰素、全口服的直接抗病毒药物(DAA)方案中也包含利巴韦林(RBV)。我们调查了肾功能不全对189例接受RBV-DAA联合方案治疗的HCV 2型感染患者病毒学疗效及不良反应的影响。

方法

根据估算肾小球滤过率(eGFR)定义的基线肾功能,比较RBV诱导的贫血发生率、RBV剂量减少情况及病毒学疗效。

结果

肾功能不全(eGFR = 30 - 59 mL/min/1.73 m²)患者的RBV剂量减少率更高,血红蛋白水平下降更明显。这些发现在ITPA CC基因型患者中更为显著,他们对RBV诱导的贫血更敏感。尽管总体上根据肾功能的持续病毒学应答(SVR)率无统计学显著差异(P = 0.1650),但需要减少RBV剂量的患者的SVR率显著低于未减少剂量的患者(P < 0.0001)。

结论

即使在不含干扰素的DAA方案时代,基线肾功能不全仍可能因RBV剂量减少风险增加而对慢性HCV感染患者的RBV-DAA治疗结果产生不利影响。

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