Absence of differences in the recurrence rates of hepatitis C virus‑associated hepatocellular carcinoma between direct‑acting antivirals and interferon‑based treatments: A multicenter study

Nakazawa,Atsushi; Fujioka,Shinichi; Notsumata,Kazuo; Shima,Toshihide; Yanagita,Kimihiko; Kawaguchi,Masanori; Tahara,Toshiyuki; Oomoto,Masaki; Ishikawa,Toru; Kawana,Ichiro; Tsukada,Nobuhiro; Funakoshi,Shinsuke; Itoh,Hiroyuki; Nagano,Tomoo; Horie,Yutaka; Tatemichi,Masayuki; Yamamoto,Kazuhide; Okanoue,Takeshi

doi:10.3892/wasj.2021.98

Absence of differences in the recurrence rates of hepatitis C virus‑associated hepatocellular carcinoma between direct‑acting antivirals and interferon‑based treatments: A multicenter study

Authors:
- Atsushi Nakazawa
- Shinichi Fujioka
- Kazuo Notsumata
- Toshihide Shima
- Kimihiko Yanagita
- Masanori Kawaguchi
- Toshiyuki Tahara
- Masaki Oomoto
- Toru Ishikawa
- Ichiro Kawana
- Nobuhiro Tsukada
- Shinsuke Funakoshi
- Hiroyuki Itoh
- Tomoo Nagano
- Yutaka Horie
- Masayuki Tatemichi
- Kazuhide Yamamoto
- Takeshi Okanoue
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Affiliations: Department of Internal Medicine, Saiseikai Central Hospital, Tokyo 108‑0073, Japan, Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama 700‑8511, Japan, Department of Internal Medicine, Fukui‑ken Saiseikai Hospital, Fukui 918‑8503, Japan, Department of Gastroenterology and Hepatology, Osaka Saiseikai Suita Hospital, Osaka 564‑0013, Japan, Department of Internal Medicine, Saiseikai Karatsu Hospital, Karatsu, Saga 847‑0852, Japan, Department of Gastroenterology, Saiseikai Wakayama Hospital, Wakayama 640‑8158, Japan, Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi 321‑0974, Japan, Department of Internal Medicine and Gastroenterology, Saiseikai Imabari Hospital, Imabari, Ehime 799‑1502, Japan, Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950‑1104, Japan, Department of Gastroenterology, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Kanagawa 234‑0054, Japan, Department of Internal Medicine, Saiseikai Kure Hospital, Kure, Hiroshima 737‑0821, Japan, Department of Internal Medicine, Kamisu Saisekai Hospital, Kamisu, Ibaraki 314‑0112, Japan, Department of Gastroenterology, Shimaneken Saiseikai Gotsu General Hospital, Gotsu, Shimane 695‑0011, Japan, Department of Preventive Medicine, Tokai University School of Medicine, Isehara, Kanagawa, 259‑1193, Japan
Published online on: April 2, 2021 https://doi.org/10.3892/wasj.2021.98
Article Number: 27
Copyright: © Nakazawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Direct‑acting antivirals (DAAs) have a high rate of achieving a sustained virological response (SVR) to hepatitis C virus (HCV). However, there is a possibility that the rapid elimination of HCV by DAAs can decrease internal interferon (IFN) secretion, resulting in an increased rate of hepatocellular carcinoma (HCC) recurrence than that observed with the current IFN‑based treatment. The present study aimed to retrospectively confirm the absence of differences in the recurrence rates of HCC between patients receiving DAAs and IFN‑based treatment, and to investigate the possible risk factors for recurrence. The HCC recurrence rate following treatment was compared between patients who underwent DAA therapy (DAA group, n=257) and those who received an IFN‑based regimen (IFN group, n=47). Kaplan‑Meier analysis and the log‑rank test were used to compare the groups, and baseline confounds were adjusted by Cox proportional methods. Further comparison of the HCC recurrence rate between the DAA and IFN groups was performed after adjusting these potential confounding variables using propensity score matching. Kaplan‑Meier analysis revealed no significant differences in the HCC recurrence rate between the two groups, as well as no significant difference following the adjustment of the confounding variables. In addition, significant independent risk factors were identified for recurrence in the DAA group, including proteins induced by vitamin K absence or antagonist‑II, the number of previous HCC treatments and the Forns index. Following the adjustment for risk factors for HCC recurrence among the patients in the DAA group, no significant differences in the rate were observed between the DAA and IFN groups. On the whole, these results suggested that HCC recurrence following curative treatment was equivalent in patients treated with DAAs and those treated with IFN. The Forns index was identified as a novel risk factor for HCC recurrence following DAA treatment.

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