Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study

Masanori Atsukawa; Akihito Tsubota; Chisa Kondo; Hidenori Toyoda; Makoto Nakamuta; Koichi Takaguchi; Tsunamasa Watanabe; Atsushi Hiraoka; Haruki Uojima; Toru Ishikawa; Motoh Iwasa; Toshifumi Tada; Akito Nozaki; Makoto Chuma; Shinya Fukunishi; Akira Asai; Toru Asano; Chikara Ogawa; Hiroshi Abe; Naoki Hotta; Toshihide Shima; Etsuko Iio; Shigeru Mikami; Yoshihiko Tachi; Shinichi Fujioka; Hironao Okubo; Noritomo Shimada; Joji Tani; Isao Hidaka; Akio Moriya; Kunihiko Tsuji; Takehiro Akahane; Naoki Yamashita; Tomomi Okubo; Taeang Arai; Kiyoshi Morita; Kazuhito Kawata; Yasuhito Tanaka; Takeshi Okanoue; Shin Maeda; Takashi Kumada; Katsuhiko Iwakiri; KTK49 Liver Study Group

doi:10.1007/s40121-020-00329-y

Real-World Clinical Application of 12-Week Sofosbuvir/Velpatasvir Treatment for Decompensated Cirrhotic Patients with Genotype 1 and 2: A Prospective, Multicenter Study

Infect Dis Ther. 2020 Dec;9(4):851-866. doi: 10.1007/s40121-020-00329-y. Epub 2020 Sep 8.

Authors

Masanori Atsukawa^#¹, Akihito Tsubota^#², Chisa Kondo³, Hidenori Toyoda⁴, Makoto Nakamuta⁵, Koichi Takaguchi⁶, Tsunamasa Watanabe⁷, Atsushi Hiraoka⁸, Haruki Uojima⁹, Toru Ishikawa¹⁰, Motoh Iwasa¹¹, Toshifumi Tada¹², Akito Nozaki¹³, Makoto Chuma¹³, Shinya Fukunishi¹⁴, Akira Asai¹⁴, Toru Asano¹⁵, Chikara Ogawa¹⁶, Hiroshi Abe¹⁷, Naoki Hotta¹⁸, Toshihide Shima¹⁹, Etsuko Iio²⁰, Shigeru Mikami²¹, Yoshihiko Tachi²², Shinichi Fujioka²³, Hironao Okubo²⁴, Noritomo Shimada²⁵, Joji Tani²⁶, Isao Hidaka²⁷, Akio Moriya²⁸, Kunihiko Tsuji²⁹, Takehiro Akahane³⁰, Naoki Yamashita⁵, Tomomi Okubo³, Taeang Arai³, Kiyoshi Morita³¹, Kazuhito Kawata^{32

33}, Yasuhito Tanaka²⁰, Takeshi Okanoue¹⁹, Shin Maeda¹³, Takashi Kumada⁴, Katsuhiko Iwakiri³; KTK49 Liver Study Group

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. [email protected].
² Core Research Facilities for Basic Science, The Jikei University School of Medicine, Tokyo, Japan. [email protected].
³ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
⁴ Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
⁵ National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
⁶ Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan.
⁷ Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
⁸ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan.
⁹ Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
¹⁰ Department of Hepatology, Saiseikai Niigata Hospital, Niigata, Japan.
¹¹ Department of Gastroenterology and Hepatology, Mie University School of Medicine, Mie, Japan.
¹² Department of Gastroenterology, Himeji Red Cross Hospital, Hyogo, Japan.
¹³ Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
¹⁴ Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan.
¹⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
¹⁶ Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan.
¹⁷ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shinmatusdo Central General Hospital, Matsudo, Japan.
¹⁸ Division of Hepatology, Department of Internal Medicine, Masuko Memorial Hospital, Nagoya, Japan.
¹⁹ Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Japan.
²⁰ Department of Virology and Liver Unit, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
²¹ Division of Gastroenterology, Department of Internal Medicine, Kikkoman General Hospital, Noda, Japan.
²² Bantane Hospital, Fujita Health University School of Medicine, Nagoya, Japan.
²³ Department of Gastroenterology, Okayama Saiseikai General Hospital, Okayama, Japan.
²⁴ Department of Gastroenterology, Juntendo Nerima University Hospital, Tokyo, Japan.
²⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Otakanomori Hospital, Kashiwa, Japan.
²⁶ Department of Gastroenterology, Kagawa University Graduate School of Medicine, Kita-gun, Kagawa, Japan.
²⁷ Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
²⁸ Department of Gastroenterology, Mitoyo General Hospital, Kannonji, Japan.
²⁹ Gastroenterology Center, Teine Keijinkai Hospital, Sapporo, Japan.
³⁰ Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Japan.
³¹ Gastroenterology, Toyota Kosei Hospital, Toyota, Japan.
³² Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan.
³³ KTK49 Liver Study Group, Kanto-Tokai-Shikoku-Kyushu, Japan.

^# Contributed equally.

Abstract

Introduction: Clinical trials of direct-acting antivirals for patients with decompensated cirrhosis have been conducted, but there is limited information on the medicinal applications in clinical settings. We aimed to evaluate the safety and efficacy of sofosbuvir/velpatasvir for decompensated cirrhotic patients with genotypes 1 and 2 in real-world clinical practice.

Methods: A prospective, multicenter study of 12-week sofosbuvir/velpatasvir was conducted for patients with decompensated cirrhosis at 33 institutions.

Results: The cohort included 71 patients (52 genotype 1, 19 genotype 2): 7 with Child-Pugh class A, 47 with class B, and 17 with class C (median score 8; range 5-13). The albumin-bilirubin (ALBI) score ranged from - 3.01 to - 0.45 (median - 1.58). Sixty-nine patients (97.2%) completed treatment as scheduled. The overall rate of sustained virologic response at 12 weeks post-treatment (SVR12) was 94.4% (67/71). SVR12 rates in the patients with Child-Pugh classes A, B, and C were 85.7%, 97.9%, and 88.2%, respectively. Among 22 patients with a history of hepatocellular carcinoma treatment, 20 (90.9%) achieved SVR12. The Child-Pugh score and ALBI grade significantly improved after achieving SVR12 (p = 7.19 × 10^-4 and 2.42 × 10^-4, respectively). Notably, the use of diuretics and branched-chain amino acid preparations significantly reduced after achieving SVR12. Adverse events were observed in 19.7% of the patients, leading to treatment discontinuation in two patients with cholecystitis and esophageal varices rupture, respectively.

Conclusion: Twelve weeks of sofosbuvir/velpatasvir in real-world clinical practice yielded high SVR rates and acceptable safety profiles in decompensated cirrhotic patients with genotypes 1 and 2. Achievement of SVR not only restored the liver functional reserve but also reduced or spared the administration of drugs for related complications.

Trial registration: UMIN registration no, 000038587.

Keywords: ALBI grade; Child–Pugh class; Decompensated cirrhosis; Hepatitis C virus; Sofosbuvir; Velpatasvir.