Real-world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group

Toshie Mashiba; Kouji Joko; Masayuki Kurosaki; Hironori Ochi; Chitomi Hasebe; Takehiro Akahane; Tetsuro Sohda; Keiji Tsuji; Akeri Mitsuda; Hiroyuki Kimura; Ryoichi Narita; Chikara Ogawa; Koichiro Furuta; Masaya Shigeno; Hiroaki Okushin; Hiroshi Ito; Atsunori Kusakabe; Takashi Satou; Chiharu Kawanami; Ryo Nakata; Haruhiko Kobashi; Takashi Tamada; Yasushi Ide; Hitoshi Yagisawa; Atsuhiro Morita; Tomomichi Matsushita; Kazuhiko Okada; Namiki Izumi

doi:10.1111/hepr.13362

Real-world efficacy of elbasvir and grazoprevir for hepatitis C virus (genotype 1): A nationwide, multicenter study by the Japanese Red Cross Hospital Liver Study Group

Hepatol Res. 2019 Oct;49(10):1114-1120. doi: 10.1111/hepr.13362. Epub 2019 Jun 14.

Authors

Toshie Mashiba¹, Kouji Joko¹, Masayuki Kurosaki², Hironori Ochi¹, Chitomi Hasebe³, Takehiro Akahane⁴, Tetsuro Sohda⁵, Keiji Tsuji⁶, Akeri Mitsuda⁷, Hiroyuki Kimura⁸, Ryoichi Narita⁹, Chikara Ogawa¹⁰, Koichiro Furuta¹¹, Masaya Shigeno¹², Hiroaki Okushin¹³, Hiroshi Ito¹⁴, Atsunori Kusakabe¹⁵, Takashi Satou¹⁶, Chiharu Kawanami¹⁷, Ryo Nakata¹⁸, Haruhiko Kobashi¹⁹, Takashi Tamada²⁰, Yasushi Ide²¹, Hitoshi Yagisawa²², Atsuhiro Morita²³, Tomomichi Matsushita²⁴, Kazuhiko Okada²⁵, Namiki Izumi²

Affiliations

¹ Center for Liver-Biliary-Pancreatic Disease, Matsuyama Red Cross Hospital, Ehime, Japan.
² Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
³ Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan.
⁴ Department of Gastroenterology, Ishinomaki Red Cross Hospital, Miyagi, Japan.
⁵ Hepatology Division, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
⁶ Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan.
⁷ Department of Internal Medicine, Japanese Red Cross Tottori Hospital, Tottori, Japan.
⁸ Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
⁹ Department of Gastroenterology, Oita Red Cross Hospital, Oita, Japan.
¹⁰ Department of Gastroenterology, Takamatsu Red Cross Hospital, Kagawa, Japan.
¹¹ Department of Internal Medicine, Masuda Red Cross Hospital, Shimane, Japan.
¹² Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan.
¹³ Department of Gastroenterology, Japanese Red Cross Society Himeji Hospital, Hyogo, Japan.
¹⁴ Department of Gastroenterology, Fukaya Red Cross Hospital, Saitama, Japan.
¹⁵ Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Aichi, Japan.
¹⁶ Department of Gastroenterology, Nasu Red Cross Hospital, Tochigi, Japan.
¹⁷ Department of Gastroenterology, Otsu Red Cross Hospital, Shiga, Japan.
¹⁸ Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan.
¹⁹ Department of Gastroenterology, Japanese Red Cross Okayama Hospital, Okayama, Japan.
²⁰ Department of Gastroenterology, Takatsuki Red Cross Hospital, Takatsuki, Japan.
²¹ Department of Internal Medicine, Karatsu Red Cross Hospital, Saga, Japan.
²² Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan.
²³ Department of Gastroenterology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
²⁴ Department of Gastroenterology, Japanese Red Cross Gifu Hospital, Gifu, Japan.
²⁵ Department of Gastroenterology, Toyama Red Cross Hospital, Toyama, Japan.

Abstract

Aim: The present study aimed to determine the real-world efficacy and safety of the non-structural protein (NS)5A inhibitor elbasvir (EBR) combined with the NS3/4A protease inhibitor grazoprevir (GZR) in patients with hepatitis C virus (HCV) genotype 1 (GT1) infection.

Methods: This study retrospectively evaluated the rate of sustained virologic response at 12 weeks post-treatment (SVR12) and the safety of EBR/GZR treatment in 159 men and 194 women with a median age of 72 years, and it assessed factors associated with the SVR12 rate. The attending physicians were responsible for selecting candidate patients for EBR/GZR in this retrospective study.

Results: Treatment outcomes for EBR/GZR were good in direct-acting antiviral (DAA)-naïve patients, of whom 99.4% achieved SVR. Of 353 patients, 10 (2.9%) had treatment failure. Of these patients, eight previously underwent DAA therapy, and the remaining two had NS5A-L31/Y93 double mutation. The SVR rate was 50% (8/16 patients) in patients who previously underwent DAA therapy, and 18.2% (2/11 patients) in patients with NS5A-L31/Y93 double mutation. On multivariate logistic regression analysis, NS5A-Y31/Y93 double mutation (odds ratio 356.3; 95% confidence interval, 23.91-16 940; P < 0.0001) was identified as an independent predictor of treatment failure. No serious adverse events were observed with EBR/GZR therapy.

Conclusions: The SVR rate of EBR/GZR would have been 100% in patients without either a history of DAA therapy or double mutation. This combination of drugs could be safely given and is, thus, considered a highly useful first-line treatment for DAA-naïve patients with HCV.

Keywords: elbasvir; genotype 1; grazoprevir; hepatitis C virus; resistance-associated substitution.

Grants and funding

Japan Agency for Medical Research and Development (AMED)