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Natural history of lean and non-lean metabolic dysfunction-associated steatotic liver disease

  • Original Article―Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Conflicting evidence regarding the prognosis of lean metabolic dysfunction-associated steatotic liver disease (MASLD) has raised substantial questions.

Aim

This study aimed to elucidate the prognosis of lean MASLD by conducting a comprehensive analysis of a vast Asian cohort.

Methods

This study used a nationwide, population-based database and analyzed 2.9 million patients. The primary endpoints were liver-related events (LREs) and cardiovascular events (CVEs) in patients with lean MASLD, non-lean MASLD, and normal liver control groups.

Results

The median observation period was 4.2 years. The 5-year incidence values of LREs in the lean MASLD, non-lean MASLD, and normal liver control groups were 0.065%, 0.039%, and 0.006%, respectively. The LRE risk of lean MASLD was significantly higher than that of normal liver control (adjusted hazard ratio [aHR]: 5.94, 95% confidence interval [CI]: 3.95–8.92) but comparable to that of non-lean MASLD (aHR: 1.35, 95% CI: 0.87–2.08). By contrast, for CVEs, the non-lean MASLD group exhibited a higher 5-year cumulative incidence rate (0.779%) than the lean MASLD (0.600%) and normal liver control (0.254%) groups. The lean MASLD group had a reduced risk of CVEs compared with the non-lean MASLD group (aHR, 0.73; 95% CI: 0.64–0.84), and comparable risk of CVEs to the normal liver control group (aHR, 0.99; 95% CI: 0.88–1.12).

Conclusion

Lean MASLD exhibits a similar LRE risk and a lower CVE risk to non-lean MASLD. Therefore, follow-up and treatment strategies should be tailored to the specific MASLD condition.

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Abbreviations

aHR:

Adjusted hazard ratio

BMI:

Body mass index

CVEs:

Cardiovascular events

CI:

Confidence interval

DM:

Diabetes mellitus

HL:

Hyperlipidemia

HT:

Hypertension

ICD-10:

International Classification of Diseases 10th Revision

LRE:

Liver-related events

MASLD:

Metabolic dysfunction-associated steatotic liver disease

NAFLD:

Nonalcoholic fatty liver disease

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Funding

Nobuharu Tamaki receives funding support from Japan Agency for Medical Research and Development (grant number: JP23fk0210111h0002, JP23fk0210104s0202) and Japanese Ministry of Health, Welfare and Labor (grant number: 23HC2002, 23HC2003). Masayuki Kurosaki receives funding support from Japan Agency for Medical Research and Development (grant number: JP23fk0210123h0001). Namiki Izumi receives funding support from Japanese Ministry of Health, Welfare and Labor (grand number: 23HC2001). Takeji Umemura receives funding support from Japan Agency for Medical Research and Development (grant number: JP23fk0210125).

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Author notes

  1. Shun-Ichi Wakabayashi, Nobuharu Tamaki, and Takefumi Kimura have contributed equally to the study.

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Shinshu University School of Medicine, Nagano, Japan

    Shun-Ichi Wakabayashi, Takefumi Kimura & Takeji Umemura

  2. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, 1-26-1 Kyonan-Cho, Musashino-Shi, Tokyo, 180-8610, Japan

    Nobuharu Tamaki, Masayuki Kurosaki & Namiki Izumi

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  1. Shun-Ichi Wakabayashi
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  5. Masayuki Kurosaki
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Contributions

Study concept and design: SIW, NT, TK, MK, and NI; Data analysis: SIW, NT, and TK; data interpretation: SIW, NT, and TK; drafting of the manuscript: SIW, NT, TK; critical revision of the manuscript: SIW, NT, SIW, TK, TU, MK, and NI; statistical analysis: SIW, NT, and TK; study supervision: MK, TU, and NI; obtained funding: NT, TU, MK, and NI; all authors had access to the study data and reviewed and approved the final manuscript.

Corresponding author

Correspondence to Masayuki Kurosaki.

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Supplementary Information

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Supplementary Figure 1

: Cumulative incidence of hepatocarcinogenic events. Lean, lean MASLD; non-lean, non-lean MASLD. Supplementary Figure 2: Cumulative incidence of ascites and encephalopathy events. Lean, lean MASLD; non-lean, non-lean MASLD. Supplementary Figure 3: Cumulative incidence of variceal bleeding events. Lean, lean MASLD; non-lean, non-lean MASLD. (PPTX 2548 KB)

Supplementary file2 (DOCX 33 KB)

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Wakabayashi, SI., Tamaki, N., Kimura, T. et al. Natural history of lean and non-lean metabolic dysfunction-associated steatotic liver disease. J Gastroenterol (2024). https://doi.org/10.1007/s00535-024-02093-z

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