Agile 3+ and Agile 4, noninvasive tests for liver fibrosis, are excellent formulae to predict liver-related events in nonalcoholic fatty liver disease

Kouichi Miura; Hideki Hayashi; Yoshihiro Kamada; Hideki Fujii; Hirokazu Takahashi; Satoshi Oeda; Michihiro Iwaki; Takumi Kawaguchi; Eiichi Tomita; Masato Yoneda; Akihiro Tokushige; Shinichiro Ueda; Shinichi Aishima; Yoshio Sumida; Atsushi Nakajima; Takeshi Okanoue; Japan Study Group of Nonalcoholic Fatty Liver Disease

doi:10.1111/hepr.13938

Agile 3+ and Agile 4, noninvasive tests for liver fibrosis, are excellent formulae to predict liver-related events in nonalcoholic fatty liver disease

Hepatol Res. 2023 Oct;53(10):978-988. doi: 10.1111/hepr.13938. Epub 2023 Jul 12.

Authors

Kouichi Miura¹, Hideki Hayashi², Yoshihiro Kamada³, Hideki Fujii⁴, Hirokazu Takahashi⁵, Satoshi Oeda⁵, Michihiro Iwaki⁶, Takumi Kawaguchi⁷, Eiichi Tomita², Masato Yoneda⁶, Akihiro Tokushige⁸, Shinichiro Ueda⁸, Shinichi Aishima⁹, Yoshio Sumida¹⁰, Atsushi Nakajima⁶, Takeshi Okanoue¹¹; Japan Study Group of Nonalcoholic Fatty Liver Disease

Affiliations

¹ Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan.
² Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan.
³ Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
⁴ Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
⁵ Liver Center, Saga University Hospital, Saga, Japan.
⁶ Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
⁷ Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
⁸ Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus School of Medicine, Okinawa, Japan.
⁹ Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
¹⁰ Graduate School of Healthcare and Welfare Management, International University of Healthcare and Welfare, Tokyo, Japan.
¹¹ Department of Gastroenterology, Saiseikai Suita Hospital, Suita, Japan.

PMID: 37353881
DOI: 10.1111/hepr.13938

Abstract

Aim: The noninvasive tests (NITs) Agile 3+ and Agile 4 effectively identify patients with nonalcoholic fatty liver disease (NAFLD) complicated with advanced fibrosis (F3-4) and cirrhosis (F4), respectively. Little information is available on associations between Agile scores and intra-/extrahepatic events. The aim of this study was to determine the predictive performance of Agile scores for intra-/extrahepatic events in Asian patients with biopsy-proven NAFLD.

Methods: We undertook a retrospective multicenter cohort study to investigate associations between intra-/extrahepatic events and two Agile scores, Agile 3+ and Agile 4. The scores were obtained by combining clinical parameters and liver stiffness measurement using transient elastography.

Results: Among 403 enrolled patients, 11 had liver-related events (LREs), including seven with hepatocellular carcinoma (HCC). The incidence of LREs and HCC showed a stepwise increase in the advanced fibrosis group (F3-4), Agile 3+ rule-in (F3-4, highly suspected), and Agile 4 rule-in (F4, highly suspected) groups, compared to their counterparts. Hazard ratios for LREs in the advanced fibrosis group, Agile 3+ rule-in, and Agile 4 rule-in groups were 4.05 (p = 0.03), 23.5 (p = 0.003), and 45.5 (p < 0.001), respectively. The predictive performance results for Agile 3+ and Agile 4 were 0.780 and 0.866, respectively, which were higher than for fibrosis (0.595). Unlike for LREs, Agile scores failed to identify patients with extrahepatic events, including cardiovascular events and extrahepatic cancer.

Conclusions: Agile 3+ and Agile 4 scores are excellent NITs for predicting LREs in patients with NAFLD, possibly without histological assessment.

Keywords: Agile score; NAFLD; comorbidity; fibrosis; noninvasive test.

Grants and funding

KAKENHI