Impact of Obesity and Heavy Alcohol Consumption on Hepatocellular Carcinoma Development after HCV Eradication with Antivirals

Tatsuya Minami; Ryosuke Tateishi; Naoto Fujiwara; Ryo Nakagomi; Takuma Nakatsuka; Masaya Sato; Koji Uchino; Kenichiro Enooku; Hayato Nakagawa; Hidetaka Fujinaga; Masashi Izumiya; Kazuyuki Hanajiri; Yoshinari Asaoka; Yuji Kondo; Yasuo Tanaka; Motoyuki Otsuka; Takamasa Ohki; Masahiro Arai; Atsushi Tanaka; Kiyomi Yasuda; Hideaki Miura; Itsuro Ogata; Toshiro Kamoshida; Kazuaki Inoue; Yukihiro Koike; Masatoshi Akamatsu; Hiroshi Mitsui; Hajime Fujie; Keiji Ogura; Hideo Yoshida; Tomonori Wada; Kiyohiko Kurai; Hisato Maekawa; Shuntaro Obi; Takuma Teratani; Naohiko Masaki; Kayo Nagashima; Takashi Ishikawa; Naoya Kato; Kyoji Moriya; Hiroshi Yotsuyanagi; Kazuhiko Koike

doi:10.1159/000513705

Impact of Obesity and Heavy Alcohol Consumption on Hepatocellular Carcinoma Development after HCV Eradication with Antivirals

Liver Cancer. 2021 Jul;10(4):309-319. doi: 10.1159/000513705. Epub 2021 Jun 4.

Authors

Tatsuya Minami¹, Ryosuke Tateishi¹, Naoto Fujiwara¹, Ryo Nakagomi¹, Takuma Nakatsuka¹, Masaya Sato¹, Koji Uchino¹, Kenichiro Enooku¹, Hayato Nakagawa¹, Hidetaka Fujinaga¹, Masashi Izumiya¹, Kazuyuki Hanajiri^{1

2}, Yoshinari Asaoka^{1

3}, Yuji Kondo^{1

4}, Yasuo Tanaka¹, Motoyuki Otsuka¹, Takamasa Ohki⁵, Masahiro Arai⁶, Atsushi Tanaka³, Kiyomi Yasuda⁷, Hideaki Miura⁸, Itsuro Ogata⁹, Toshiro Kamoshida¹⁰, Kazuaki Inoue¹¹, Yukihiro Koike¹², Masatoshi Akamatsu¹³, Hiroshi Mitsui¹⁴, Hajime Fujie¹⁵, Keiji Ogura¹⁶, Hideo Yoshida¹⁷, Tomonori Wada², Kiyohiko Kurai¹⁸, Hisato Maekawa¹⁹, Shuntaro Obi⁴, Takuma Teratani²⁰, Naohiko Masaki²¹, Kayo Nagashima²², Takashi Ishikawa²³, Naoya Kato¹, Kyoji Moriya¹, Hiroshi Yotsuyanagi²⁴, Kazuhiko Koike¹

Affiliations

¹ Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
² Department of Gastroenterology, Sanraku Hospital, Tokyo, Japan.
³ Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
⁴ Department of Gastroenterology and Hepatology, Kyoundo Hospital, Tokyo, Japan.
⁵ Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan.
⁶ Department of Gastroenterology, Toshiba General Hospital, Toshiba, Japan.
⁷ Department of Gastroenterology, Kiyokawa Hospital, Tokyo, Japan.
⁸ Department of Gastroenterology, Tokyo Yamate Medical Center, Tokyo, Japan.
⁹ Department of Gastroenterology, Kawakita General Hospital, Tokyo, Japan.
¹⁰ Department of Gastroenterology, Hitachi General Hospital, Hitachi, Japan.
¹¹ Department of Gastroenterology, Showa University Fujigaoka Hospital, Yokohama, Japan.
¹² Department of Gastroenterology, Kanto Central Hospital of the Mutual Aid Association of Public School Teacher, Tokyo, Japan.
¹³ Department of Gastroenterology, JR Tokyo General Hospital, Tokyo, Japan.
¹⁴ Department of Gastroenterology, Tokyo Teishin Hospital, Tokyo, Japan.
¹⁵ Department of Gastroenterology, Tokyo Shinjuku Medical Center, Tokyo, Japan.
¹⁶ Department of Gastroenterology, Tokyo Metropolitan Police Hospital, Tokyo, Japan.
¹⁷ Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan.
¹⁸ Kurai Kiyohiko Medical Clinic, Utsunomiya, Japan.
¹⁹ Department of Gastroenterology and Hepatology, Tokyo Takanawa Hospital, Tokyo, Japan.
²⁰ Department of Hepato-Biliary-Pancreatic medicine, NTT Medical Center Tokyo, Tokyo, Japan.
²¹ Clinical Laboratory Department, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
²² Department of Gastroenterology, National Disaster Medical Center, Tachikawa, Japan.
²³ Marunouchi Clinic, Tokyo, Japan.
²⁴ Division of Infectious Disease and Applied Immunology, The Institute of Medical Science Research Hospital, The University of Tokyo, Tokyo, Japan.

Abstract

Background and aims: It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy.

Methods: In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively.

Results: Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m²) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51-4.25) and 2.56 (95% CI: 1.14-5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61-2.33).

Conclusions: Obesity and heavy alcohol consumption increased the risk of HCC development after SVR.

Keywords: Direct-acting antivirals; Hepatitis C; Hepatocellular carcinoma; Obesity.