Glecaprevir and pibrentasvir combination therapy for hepatitis C virus-infected Japanese patients on hemodialysis

Yoshiaki Tanaka,Yasuhiro Yamanouchi,Ji Hyun Sung,Togo Aoyama,Tomoaki Fujikawa,Naohisa Wada,Takayasu Ohtake,Haruki Uojima,Kousuke Kubota,Wasaburo Koizumi,Makoto Kako,Akitaka Shibuya,Takanori Masaki,Hisashi Hidaka,Takahide Nakazawa,Shuzo Kobayashi,Yasuo Takeuchi

doi:10.1186/s41100-018-0193-4

Abstract

BackgroundIt remains unclear whether hepatitis C virus (HCV)-infected Japanese patients on hemodialysis (HD) have an altered viral response to glecaprevir (GLE) and pibrentasvir (PIB) combination therapy and whether this treatment is safe for this patient group. Therefore, we investigated the characteristics associated with virological response to GLE and PIB combination therapy for HCV in Japanese patients undergoing HD. This study aimed to evaluate the safety and efficacy of GLE and PIB combination therapy in HCV-infected Japanese patients on HD.MethodsThis multicenter, single-arm, open-label, and prospective study was conducted at four centers in Japan and enrolled Japanese patients with chronic HCV genotype 1b, 2a, and 2b infections. Enrolled patients received 300 mg GLE in combination with 120 mg PIB once daily for either 8 or 12 weeks. The primary endpoint of this trial was the rate of sustained virological response at 12 weeks after treatment (SVR12). Furthermore, pharmacological effects and adverse events associated with combination therapy were evaluated.ResultsA total of 18 HD patients with HCV infection were enrolled in this study. Of these patients, 17 (94.4%) achieved SVR12. Among patients receiving combination therapy for 8 weeks, only one experienced a virological relapse at week 12 after the end of treatment. Despite the absence of treatment-related deaths, adverse events were observed in 9 patients (50.0%) during treatment. The most frequent adverse event was pruritus, which occurred in 7 patients (38.9%).ConclusionsGLE and PIB combination therapy was effective and tolerable in Japanese HD patients with chronic HCV genotype 1b, 2a, and 2b infections.Trial registrationThis study was registered at the UMIN Clinical Trials Registry as UMIN000029781 (registered 21 November 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034026).

Highlights

It remains unclear whether hepatitis C virus (HCV)-infected Japanese patients on hemodialysis (HD) have an altered viral response to glecaprevir (GLE) and pibrentasvir (PIB) combination therapy and whether this treatment is safe for this patient group
In Japan, several combined regimens, including daclatasvir (DCV)/asunaprevir (ASV), ombitasvir/paritaprevir/ ritonavir, and elbasvir/grazoprevir, which are primarily eliminated by hepatic metabolism, are available for the effective treatment of HD patients with hepatitis C virus (HCV) genotype 1b infections [6,7,8]
Characteristics of patients Among 1022 HD patients who were serologically tested in 16 dialysis facilities using third-generation enzymelinked immunosorbent assay, 56 (5.5%) and 20 (2.0%) patients tested positive for hepatitis C antibody and HCV RNA, respectively

Summary

Introduction

It remains unclear whether hepatitis C virus (HCV)-infected Japanese patients on hemodialysis (HD) have an altered viral response to glecaprevir (GLE) and pibrentasvir (PIB) combination therapy and whether this treatment is safe for this patient group. The EXPEDITION-4 trial in patients with HCV genotype 1–5 or 6 infection has reported the safety and efficacy of 12-week GLE and PIB combination therapy as treatment for chronic HCV in patients undergoing HD, showing dramatically improved rates of SVR at 12 weeks after treatment (SVR12) [12]. This regimen is expected to yield beneficial results in specific populations, such as HCV genotype 2-infected Japanese patients with insufficient renal function.

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