Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group.

Toshie Mashiba,Kazuhiko Okada,Ryuichi Narita,Chikara Ogawa,Hironori Ochi,Masaya Shigeno,Takashi Satou,Yukio Osaki,Yuji Kojima,Namiki Izumi,Tetsuro Sohda,Chiharu Kawanami,Akeri Mitsuda,Masayuki Kurosaki,Yasushi Uchida,Keiji Tsuji,Hiroyuki Kimura,Takehiko Abe,Akahane Takehiro,Atsunori Kusakabe,Yasushi Ide,Tadashi Kitamura,Kouji Joko,Rieko Nakata ,Tetsuhiro Goto

doi:10.1371/journal.pone.0194704

Abstract

Background and aimThis study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort.MethodsThis multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively.ResultsAFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients.ConclusionsThere were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Highlights

Since the era in which interferon (IFN) was the standard treatment for hepatitis C, attempts have been made to eliminate hepatitis C virus (HCV) following hepatocellular carcinoma (HCC) treatment, but it could be achieved in only a limited number of patients due to side effects
AFP at the completion of antiviral therapy, clinical stage of HCC, and non-sustained virological response (SVR) were independent factors associated with early recurrence of HCC
Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC

Summary

Introduction

Since the era in which interferon (IFN) was the standard treatment for hepatitis C, attempts have been made to eliminate hepatitis C virus (HCV) following hepatocellular carcinoma (HCC) treatment, but it could be achieved in only a limited number of patients due to side effects. Potential increases in unexpected early recurrence of HCC after HCV elimination have been reported with DAA therapy [7,8]. With this background, the HCC recurrence rate was compared between those who underwent IFN therapy and those who underwent IFN-free therapy after HCC treatment in a large-scale cohort. This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort

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Conclusion