Prospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2018; 24(13): 1478-1485
Published online Apr 7, 2018. doi: 10.3748/wjg.v24.i13.1478
Hepatocellular carcinoma or interferon-based therapy history attenuates sofosbuvir/ribavirin for Japanese genotype 2 hepatitis C virus
Masayoshi Yada, Masayuki Miyazaki, Kosuke Tanaka, Akihide Masumoto, Kenta Motomura
Masayoshi Yada, Masayuki Miyazaki, Kosuke Tanaka, Akihide Masumoto, Kenta Motomura, Department of Hepatology, Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
Author contributions: Yada M and Motomura K wrote the paper; Yada M, Miyazaki M, Tanaka K, and Motomura K analyzed the data; Masumoto A supervised writing of the paper; all authors contributed to the manuscript.
Institutional review board statement: The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected in a priori approval by the Ethics Committee of Iizuka Hospital (Approve No. 26282).
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: The authors have no disclosures to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Masayoshi Yada, MD, PhD, Doctor, Department of Hepatology, Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka 820-8505, Japan.
Telephone: +81-948-223800 Fax: +81-948-295744
Received: February 5, 2018
Peer-review started: February 5, 2018
First decision: February 26, 2018
Revised: February 26, 2018
Accepted: March 7, 2018
Article in press: March 7, 2018
Published online: April 7, 2018
Research background

Combination therapy with peg-interferon (PEG-IFN) and ribavirin (RBV) was the first-line therapy for genotype 2 hepatitis C virus (HCV) infection, but only 80% of patients achieved elimination of HCV with this treatment. The introduction of direct-acting antiviral agents has drastically improved the efficacy of treatments for chronic HCV infection. Combination therapy with NS5B RNA-dependent RNA polymerase inhibitor sofosbuvir (SOF) and RBV for patients with genotype 2 hepatitis C virus (GT2-HCV) infection was approved for clinical use in June 2015.

Research motivation

This therapy showed improved efficacy and was well tolerated in a phase 3 trial. However, predictive factor of sustained virological response (SVR) is not unclear.

Research objectives

We conducted a prospective study to investigate the efficacy and safety of sofosbuvir/ribavirin (SOF/RBV) therapy for Japanese patients with GT2-HCV infection in a real-world clinical setting.

Research methods

A total of 182 patients with GT2-HCV infection who received SOF/RBV therapy for 12 wk at our hospital were enrolled. The patients comprised 122 men and 60 women (age range: 17-84 years; mean age ± SD: 60.1 ± 12.1 years). One hundred sixty nine of 182 patients completed 12 wk treatment and were examined their virological response. To investigate predictive factors of SVR, we examined the relationships between virological response and clinical data by logistic regression analyses.

Research results

The rates of SVR at 12 wk after the end of treatment were 87.9% (intention to treat: 160/182) and 94.1% (per protocol: 159/169). Multivariate analyses showed that history of hepatocellular carcinoma (HCC) or IFN-based therapy independently reduced the efficacy of SOF/RBV therapy.

Research conclusions

This study showed Japanese IL28B single nucleotide polymorphisms had no relation to efficacy of SOF/RBV for GT2-HCV infection. Morisco et al[15] reported rapid virological response (RVR) was the only independent predictive factor of SVR in triple therapy (Telaprevir/PEG-IFN/RBV) regardless of cirrhosis. In the present study, RVR did not affect efficacy of SOF/RBV for GT2-HCV infection. The multivariate regression analysis showed that history of HCC or IFN-based therapy was independently related to non-SVR. In our study, the proportion of non-SVR patients treated by surgical resection or radiofrequency ablation tended to be lower than the proportion of non-SVR patients treated by transcatheter arterial chemoembolization or radiation for bone metastasis. Meanwhile, the rate of HCC recurrence within 1 year tended to be higher in non-SVR patients than that in SVR patients.

Research perspectives

Prenner et al reported that presence of active HCC at the start of direct acting antivirals, including SOF/RBV therapy, decreased the SVR rate. As active HCC not detected by imaging was probably related to non-SVR, monitoring is required for carcinogenesis and recurrence of HCC after the end of SOF/RBV therapy, especially in non-SVR patients.