Volume 55, Issue 5 pp. 648-662

ORIGINAL ARTICLE

Association of liver fibrosis progression with non–liver-related mortality in metabolic dysfunction-associated steatotic liver disease

Toshifumi Tada,

Corresponding Author

Toshifumi Tada

[email protected]

orcid.org/0000-0002-0976-6761

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

Correspondence

Toshifumi Tada, Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.

Email: [email protected]

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Takashi Kumada,

Takashi Kumada

orcid.org/0000-0003-2211-495X

Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan

Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Hidenori Toyoda,

Hidenori Toyoda

orcid.org/0000-0002-1652-6168

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

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Satoshi Yasuda,

Satoshi Yasuda

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

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Yuichi Koshiyama,

Yuichi Koshiyama

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

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Tomoyuki Akita,

Tomoyuki Akita

Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Yuzo Kodama,

Yuzo Kodama

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

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Junko Tanaka,

Junko Tanaka

orcid.org/0000-0002-5669-4051

Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Toshifumi Tada,

Corresponding Author

Toshifumi Tada

[email protected]

orcid.org/0000-0002-0976-6761

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

Correspondence

Toshifumi Tada, Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.

Email: [email protected]

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Takashi Kumada,

Takashi Kumada

orcid.org/0000-0003-2211-495X

Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan

Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Hidenori Toyoda,

Hidenori Toyoda

orcid.org/0000-0002-1652-6168

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

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Satoshi Yasuda,

Satoshi Yasuda

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

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Yuichi Koshiyama,

Yuichi Koshiyama

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

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Tomoyuki Akita,

Tomoyuki Akita

Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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Yuzo Kodama,

Yuzo Kodama

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

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Junko Tanaka,

Junko Tanaka

orcid.org/0000-0002-5669-4051

Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

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First published: 19 January 2025

https://doi.org/10.1111/hepr.14164

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Abstract

Aim

In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), the prognosis and outcomes, particularly non–liver-related mortality, remain insufficiently elucidated. We investigated all-cause mortality in patients with MASLD to elucidate the association of the severity of liver fibrosis with liver-related and non–liver-related mortality in MASLD.

Methods

Among 4528 participants with MASLD, we examined the causes of death and analyzed liver-related and non–liver-related mortality, stratified by the degree of fibrosis using the competing risk method. Fibrosis severity was assessed using the Fibrosis-4 (FIB-4) and FIB-3 indices.

Results

The median follow-up period was 11.7 years. Of the 4528 participants, 551 died during the follow-up period, with only 37 (6.7%) deaths attributable to liver-related diseases and 514 (93.3%) to non–liver-related causes. For the risk of hepatocellular carcinoma, the hazard ratios (HRs; 95% confidence interval [CI]) for FIB-4 were 5.67 (2.20–14.59) and 32.14 (12.40–83.35) and for FIB-3 were 5.43 (2.73–10.79) and 19.96 (10.50–37.93). For liver-related mortality, the HRs (95% CI) for FIB-4 were 6.32 (2.23–17.85) and 27.62 (9.74–78.37) and for FIB-3 were 7.15 (2.62–19.50) and 19.86 (8.12–48.55), respectively. In contrast, intermediate and high FIB-4 and FIB-3 indices were unassociated with non–liver-related mortality: HRs (95% CI) for FIB-4 were 0.85 (0.70–1.04) and 0.87 (0.64–1.18), and for FIB-3 were 0.96 (0.77–1.20) and 0.92 (95% CI, 0.64–1.31), respectively.

Conclusions

The progression of liver fibrosis was unassociated with mortality from non–liver-related causes in patients with MASLD.

Graphical Abstract

Mortality from disease-specific causes in 4528 metabolic dysfunction-associated steatotic liver disease (MASLD) was analyzed, stratified by the degrees of liver fibrosis using the Fibrosis-4 (FIB-4) and FIB-3 indices. Among the 4528 patients, 514/551 (93.3%) died from non–liver-related causes during the follow-up period. Multivariable analysis showed that the progression of liver fibrosis severity was not associated with mortality from non–liver-related causes in MASLD.

CONFLICT OF INTEREST STATEMENT

Toshifumi Tada is an editorial board member of Hepatology Research. Junko Tanaka is the ex-editorial board member of Hepatology Research. The other authors declare no conflict of interests for this article.

Open Research

DATA AVAILABILITY STATEMENT

The datasets are available from the corresponding author upon reasonable request.

Supporting Information

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Volume55, Issue5

May 2025

Pages 648-662

Filename	Description
hepr14164-sup-0001-suppl-data.pdf258.1 KB	Supporting Information S1
hepr14164-sup-0002-fig_s1.pdf77 KB	Figure S1
hepr14164-sup-0003-fig_s2.pdf95 KB	Figure S2