1
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan.
2
Center for Liver-Biliary-Pancreatic Diseases, Matsuyama Red Cross Hospital, Ehime, Japan.
3
Department of Gastroenterology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
4
Department of Gastroenterology, Japanese Red Cross Otsu Hospital, Shiga, Japan.
5
Department of Gastroenterology, Japanese Red Cross Ise Hospital, Mie, Japan.
6
Department of Gastroenterology, Japanese Red Cross Matsue Hospital, Shimane, Japan.
7
Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
8
Department of Gastroenterology, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital, Hiroshima, Japan.
9
Department of Gastroenterology, Japanese Red Cross Akita Hospital, Akita, Japan.
10
Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
11
Department of Hepatology, Japanese Red Cross Okayama Hospital, Okayama, Japan.
12
Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Miyagi, Japan.
13
Department of Gastroenterology, Japanese Red Cross Maebashi Hospital, Gunma, Japan.
14
Department of Gastroenterology, Japanese Red Cross Medical Center, Tokyo, Japan.
15
Department of Gastroenterology, Japanese Red Cross Gifu Hospital, Gifu, Japan.
16
Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Hokkaido, Japan.
17
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8610, Japan. [email protected].
PMID: 32747646 DOI: 10.1038/s41598-020-69522-w
Abstract
Nucleos(t)ide analogs (NA) suppress hepatitis B virus (HBV) replication and reduce the risk of hepatocellular carcinoma (HCC). However, NA cannot suppress carcinogenesis completely in patients with chronic hepatitis B. The aims of this study were to identify risk factors for HCC and develop a refined carcinogenesis prediction model. Patients receiving NA therapy (n = 1,183) were recruited retrospectively from the 16 hospitals. All patients had been receiving NA continuously for more than 1 year until the end of the follow-up. During a median follow-up of 4.9 (1.0-12.9) years, 52 (4.4%) patients developed HCC. A multivariate analysis revealed that male gender, older age, lower platelet counts at the baseline, and detectable HBV DNA during NA therapy were independent predictive factors of HCC development. The PAGE-B score was calculated by using these factors. 240 (20.3%), 661 (55.9%), and 282 (23.8%) patients were classified into low-, intermediate-, and high-risk groups, respectively. In the intermediate- and high-risk group, detectable HBV DNA was significantly associated with a higher risk of HCC development compared with continuously undetectable HBV DNA, respectively (HR 3.338; 95% CI 1.045-10.66/HR 3.191; 95% CI 1.543-6.597). PAGE-B-DNA, which is the combined PAGE-B and HBV DNA status, was valuable for a more refined stratification of PAGE-B.
Grant support
JP19fk0210025h0003/the Ministry of Health, Labor and Welfare in Japan and Japan Agency for Medical Research and Development