General evaluation score for predicting the development of hepatocellular carcinoma in patients with advanced liver fibrosis associated with hepatitis C virus genotype 1 or 2 after direct-acting antiviral therapy

Toshifumi Tada; Masayuki Kurosaki; Nobuharu Tamaki; Yutaka Yasui; Nami Mori; Keiji Tsuji; Chitomi Hasebe; Koji Joko; Takehiro Akahane; Koichiro Furuta; Haruhiko Kobashi; Hideki Fujii; Toru Ishii; Hiroyuki Marusawa; Masahiko Kondo; Yuji Kojima; Hideo Yoshida; Yasushi Uchida; Shinichiro Nakamura; Namiki Izumi

doi:10.1002/jgh3.12778

General evaluation score for predicting the development of hepatocellular carcinoma in patients with advanced liver fibrosis associated with hepatitis C virus genotype 1 or 2 after direct-acting antiviral therapy

JGH Open. 2022 Jun 8;6(7):487-495. doi: 10.1002/jgh3.12778. eCollection 2022 Jul.

Authors

Toshifumi Tada¹, Masayuki Kurosaki², Nobuharu Tamaki², Yutaka Yasui², Nami Mori³, Keiji Tsuji³, Chitomi Hasebe⁴, Koji Joko⁵, Takehiro Akahane⁶, Koichiro Furuta⁷, Haruhiko Kobashi⁸, Hideki Fujii⁹, Toru Ishii¹⁰, Hiroyuki Marusawa¹¹, Masahiko Kondo¹², Yuji Kojima¹³, Hideo Yoshida¹⁴, Yasushi Uchida¹⁵, Shinichiro Nakamura¹, Namiki Izumi²

Affiliations

¹ Department of Internal Medicine Japanese Red Cross Society Himeji Hospital Himeji Japan.
² Department of Gastroenterology and Hepatology Musashino Red Cross Hospital Tokyo Japan.
³ Department of Gastroenterology Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital Hiroshima Japan.
⁴ Department of Gastroenterology Japanese Red Cross Asahikawa Hospital Asahikawa Japan.
⁵ Center for Liver-Biliary-Pancreatic Disease Matsuyama Red Cross Hospital Matsuyama Japan.
⁶ Department of Gastroenterology Japanese Red Cross Ishinomaki Hospital Ishinomaki Japan.
⁷ Department of Gastroenterology Masuda Red Cross Hospital Masuda Japan.
⁸ Department of Gastroenterology Japanese Red Cross Okayama Hospital Okayama Japan.
⁹ Department of Gastroenterology Japanese Red Cross Kyoto Daiichi Hospital Kyoto Japan.
¹⁰ Department of Gastroenterology Japanese Red Cross Akita Hospital Akita Japan.
¹¹ Department of Gastroenterology and Hepatology Japanese Red Cross Osaka Hospital Osaka Japan.
¹² Department of Gastroenterology Japanese Red Cross Otsu Hospital Otsu Shiga Japan.
¹³ Department of Hepatology Japanese Red Cross Ise Hospital Ise Japan.
¹⁴ Department of Gastroenterology Japanese Red Cross Medical Center Tokyo Japan.
¹⁵ Department of Gastroenterology Japanese Red Cross Matsue Hospital Matsue Japan.

Abstract

Background and aim: To validate a composite predictive model for hepatocellular carcinoma (HCC) development in patients with advanced liver fibrosis associated with chronic hepatitis C virus (HCV) who have received direct-acting antiviral (DAA) therapy and achieved sustained virologic response (SVR).

Methods: This study included 1258 patients with advanced liver fibrosis associated with HCV genotype 1, 2, or both. General evaluation score (GES), which is based on sex, age, fibrosis stage, albumin, and α-fetoprotein, was used as a composite predictive model.

Results: There were 645 (51.3%) patients in the low-risk group, 228 (18.1%) in the intermediate-risk group, and 385 (30.6%) in the high-risk group based on GES categories. The 12-, 36-, and 60-month cumulative incidence of HCC was 0.7%, 5.3%, and 13.0%, respectively. Multivariable analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 1.863; 95% confidence interval [CI], 1.204-2.883), F4 fibrosis stage (HR, 3.199; 95% CI, 1.696-6.036), and albumin (HR, 0.489; 95% CI, 0.288-0.828) are independently associated with HCC development. The incidence of HCC differed significantly by GES-based risk category (P < 0.001). Cox proportional hazards models showed that, with the low-risk group as the referent, the HR for HCC development was 1.875 (95% CI, 1.000-3.514) in the intermediate-risk group and 2.819 (95% CI, 1.716-4.630) in the high-risk group. GES had better predictive ability for HCC development than fibrosis-4 index according to time-dependent receiver operating characteristic analysis.

Conclusion: GES is useful for predicting HCC development in patients with advanced liver fibrosis after SVR.

Keywords: advanced liver fibrosis; direct‐acting antiviral; general evaluation score; hepatitis C virus; hepatocellular carcinoma; sustained virologic response.