1 Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
2 Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. firstname.lastname@example.org.
3 Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura, 856-8562, Japan.
4 Division of Gastroenterology, National Kyusyu Medical Center Hospital, 1-8-1 Chigyouhama, Chuou-ku, Fukuoka, 810-8563, Japan.
5 Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
6 Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
7 Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
8 Third Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8556, Japan.
9 Department of Gastroenterology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hazama-machi, Yufu, 879-5593, Japan.
10 First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Azauehara, Nishihara-machi, Nakagashira-gun, 903-0215, Japan.
11 Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 850-0000, Japan.
12 Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, 890-8544, Kagoshima, Japan.
13 Department of Liver Disease, University of Miyazaki Hospital, 5200 Kihara, Kiyotake-machi, Miyazaki, 889-1692, Japan.
14 Fukuoka Tokushukai Medical Center, 4-5 Sugukita, Kasuga, 816-0864, Japan.
15 Department of Hepato-Biliary-Pancreatic Surgery and Clinical Research Institute, National Kyushu Medical Center Hospital, 1-8-1 Chigyouhama, Chuou-ku, Fukuoka, 810-8563, Japan.
16 Hepatology Division, Japanese Red Cross Fukuoka Hospital, 3-1-1 Okusu, Minami-ku, Fukuoka, 815-8555, Japan.
17 Biostatistics Center, Kurume University, 67 Asahi-machi, Kurume, 830-0011, Japan.
While achieving sustained virological response (SVR) following interferon-based or direct-acting antiviral agent (DAA) treatments reduces the incidence of hepatocellular carcinoma (HCC), an increase in unexpected early occurrence or recurrence of HCC after hepatitis C virus elimination by DAA treatments has been reported. We prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan.
Patients with chronic hepatitis C with or without cirrhosis who were treated with DAAs and obtained SVR were enrolled. DAAs were administered for 3 or 6 months. A total of 2552 patients were enrolled.
Of these, 70 patients (2.7%) developed HCC. The 12-, 24-, and 36-month cumulative HCC incidences were 1.3%, 2.9%, and 4.9% in all patients; 2.5%, 5.2%, and 10.0% in those with cirrhosis; and 0.9%, 2.1%, and 2.9% in those without cirrhosis, respectively. Multivariate analysis revealed age, sex, gamma-glutamyl transpeptidase level, and fibrosis-4 index to be independent factors associated with HCC. Patients with these four factors had an approximately six-to-sevenfold increased risk for HCC development. Five patients with large and early tumor occurrence did not receive contrast imaging examinations before treatment.
Although the results of our prospective study suggested that achieving SVR by DAA treatment reduces the incidence of HCC, HCC development still occurs. Careful follow-up is important in patients with risk factors.