Histological changes in patients who developed hepatocellular carcinoma after hepatitis C virus eradication by interferon‑based therapy

Kawaguchi,Toshihiro; Ide,Tatsuya; Kondo,Reiichiro; Nomura,Yoriko; Arinaga‑Hino,Teruko; Kuwahara,Reiichiro; Amano,Keisuke; Sano,Tomoya; Akiba,Jun; Ohshima,Koichi; Yano,Hirohisa; Torimura,Takuji

doi:10.3892/etm.2019.8024

Histological changes in patients who developed hepatocellular carcinoma after hepatitis C virus eradication by interferon‑based therapy

Authors:
- Toshihiro Kawaguchi
- Tatsuya Ide
- Reiichiro Kondo
- Yoriko Nomura
- Teruko Arinaga‑Hino
- Reiichiro Kuwahara
- Keisuke Amano
- Tomoya Sano
- Jun Akiba
- Koichi Ohshima
- Hirohisa Yano
- Takuji Torimura
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Affiliations: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan, Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830‑0011, Japan
Published online on: September 18, 2019 https://doi.org/10.3892/etm.2019.8024
Pages: 3991-4001
Copyright: © Kawaguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although the incidence of hepatocellular carcinoma (HCC) occurring after hepatitis C virus (HCV) eradication has decreased, there are still reports of hepatocarcinogenesis. The present study investigated the histological changes of non‑cancerous liver tissue obtained prior to interferon (IFN) therapy and after HCC development. A total of 669 HCV‑infected Japanese patients who achieved sustained virological response (SVR) by IFN‑based therapy were retrospectively enrolled. Of these, the present study investigated 18 patients who developed HCC after IFN‑based SVR. Specimens from 9 of 18 patients were available for histological comparisons prior to IFN therapy and following HCC development. Of these 9 patients, the specimens of 5 individuals were compared via immunohistochemical staining [CD3, CD4, CD8, CD20, forkhead box P3 (FOXP3), transforming growth factor‑β1 and granzyme B]. The current study included 6 control patients with HCV‑associated chronic liver disease who subsequently developed HCC (non‑SVR‑HCC group). Mann‑Whitney and Wilcoxon tests were used to compare groups. Bonferroni correction was used for multiple comparisons. P<0.05 was used as a critical P‑value, and following Bonferroni's correction, P<0.017 was considered to indicate a statistically significant difference. In the 9 patients examined, continuous inflammation and fibrosis were observed after HCC development. There was also a significant decrease in the positive rate of FOXP3 in all 5 patients at the time of HCC development compared with that prior to IFN therapy (P=0.0084). Additionally, there was a significant difference in the positive rate of FOXP3 between the 5 patients after HCC development and the control individuals (P=0.0022). In patients who developed HCC after IFN‑based SVR, the frequency of FOXP3 decreased, but inflammation and fibrosis remained. The extent of the reduction of FOXP3 differed in patients who developed HCC in the presence of HCV. Inflammation and fibrosis remained for a long duration after SVR, which may be associated with hepatocarcinogenesis.

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