Volume 53, Issue 10 pp. 978-988

ORIGINAL ARTICLE

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,

Kouichi Miura

Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan

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Hideki Hayashi,

Hideki Hayashi

orcid.org/0000-0003-0632-907X

Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan

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Yoshihiro Kamada,

Corresponding Author

Yoshihiro Kamada

[email protected]

orcid.org/0000-0001-5485-902X

Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Japan

Correspondence

Yoshihiro Kamada, Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Yamadaoka 1-7, Suita, Osaka 565-0871, Japan.

Email: [email protected]

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Hideki Fujii,

Hideki Fujii

Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan

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Hirokazu Takahashi,

Hirokazu Takahashi

orcid.org/0000-0002-2374-2889

Liver Center, Saga University Hospital, Saga, Japan

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Satoshi Oeda,

Satoshi Oeda

Liver Center, Saga University Hospital, Saga, Japan

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Michihiro Iwaki,

Michihiro Iwaki

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

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Takumi Kawaguchi,

Takumi Kawaguchi

orcid.org/0000-0002-7064-4325

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan

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Eiichi Tomita,

Eiichi Tomita

Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan

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Masato Yoneda,

Masato Yoneda

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

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Akihiro Tokushige,

Akihiro Tokushige

Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus School of Medicine, Okinawa, Japan

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Shinichiro Ueda,

Shinichiro Ueda

Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus School of Medicine, Okinawa, Japan

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Shinichi Aishima,

Shinichi Aishima

Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan

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Yoshio Sumida,

Yoshio Sumida

Graduate School of Healthcare and Welfare Management, International University of Healthcare and Welfare, Tokyo, Japan

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Atsushi Nakajima,

Atsushi Nakajima

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

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Takeshi Okanoue,

Takeshi Okanoue

orcid.org/0000-0002-2390-3400

Department of Gastroenterology, Saiseikai Suita Hospital, Suita, Japan

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Japan Study Group of Nonalcoholic Fatty Liver Disease,

Japan Study Group of Nonalcoholic Fatty Liver Disease

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Kouichi Miura,

Kouichi Miura

Department of Medicine, Division of Gastroenterology, Jichi Medical University, Shimotsuke, Japan

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Hideki Hayashi,

Hideki Hayashi

orcid.org/0000-0003-0632-907X

Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan

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Yoshihiro Kamada,

Corresponding Author

Yoshihiro Kamada

[email protected]

orcid.org/0000-0001-5485-902X

Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Suita, Japan

Correspondence

Yoshihiro Kamada, Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, Yamadaoka 1-7, Suita, Osaka 565-0871, Japan.

Email: [email protected]

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Hideki Fujii,

Hideki Fujii

Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan

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Hirokazu Takahashi,

Hirokazu Takahashi

orcid.org/0000-0002-2374-2889

Liver Center, Saga University Hospital, Saga, Japan

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Satoshi Oeda,

Satoshi Oeda

Liver Center, Saga University Hospital, Saga, Japan

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Michihiro Iwaki,

Michihiro Iwaki

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

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Takumi Kawaguchi,

Takumi Kawaguchi

orcid.org/0000-0002-7064-4325

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan

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Eiichi Tomita,

Eiichi Tomita

Department of Gastroenterology and Hepatology, Gifu Municipal Hospital, Gifu, Japan

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Masato Yoneda,

Masato Yoneda

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

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Akihiro Tokushige,

Akihiro Tokushige

Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus School of Medicine, Okinawa, Japan

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Shinichiro Ueda,

Shinichiro Ueda

Department of Clinical Pharmacology and Therapeutics, University of the Ryukyus School of Medicine, Okinawa, Japan

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Shinichi Aishima,

Shinichi Aishima

Department of Pathology and Microbiology, Faculty of Medicine, Saga University, Saga, Japan

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Yoshio Sumida,

Yoshio Sumida

Graduate School of Healthcare and Welfare Management, International University of Healthcare and Welfare, Tokyo, Japan

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Atsushi Nakajima,

Atsushi Nakajima

Department of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan

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Takeshi Okanoue,

Takeshi Okanoue

orcid.org/0000-0002-2390-3400

Department of Gastroenterology, Saiseikai Suita Hospital, Suita, Japan

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Japan Study Group of Nonalcoholic Fatty Liver Disease,

Japan Study Group of Nonalcoholic Fatty Liver Disease

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First published: 23 June 2023

https://doi.org/10.1111/hepr.13938

Citations: 2

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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.

Graphical Abstract

Patients with nonalcoholic fatty liver disease in high-risk groups (F3–4 of fibrosis stage, rule-in [IN] of Agile 3+, and IN of Agile 4) showed a stepwise increase of liver-related events. Hazard ratios of the high-risk groups were much higher in Agile 3+ and Agile 4 than fibrosis, compared to their counterparts.

CONFLICT OF INTEREST STATEMENT

Masato Yoneda received a research grant from Kowa Co. Ltd. Takumi Kawaguchi received honoraria from Taisho Pharmaceutical Co., Ltd., Kowa Company, Ltd., Otsuka Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., AbbVie GK., and ASKA Pharmaceutical Co., Ltd., and a research grant from Eisai Co., Ltd. The other authors declare no conflicts of interest.

Open Research

DATA AVAILABILITY STATEMENT

All datasets used and analyzed in the present study are included in the manuscript.

Supporting Information

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Citing Literature

Volume53, Issue10

October 2023

Pages 978-988