Weight Change is Associated With Metabolic Liver Health in a General Population Extending Beyond Weight Loss Targets of International Guidelines

Laurens A van Kleef; Mesut Savas; Maurice Michel; Cyrielle Caussy; Jesse Pustjens; Adriaan G Holleboom; Elisabeth F C van Rossum; Harry L A Janssen; Jörn M Schattenberg; Willem P Brouwer

doi:10.1016/j.gastha.2025.100831

Weight Change is Associated With Metabolic Liver Health in a General Population Extending Beyond Weight Loss Targets of International Guidelines

Gastro Hep Adv. 2025 Oct 10;5(2):100831. doi: 10.1016/j.gastha.2025.100831. eCollection 2026.

Authors

Laurens A van Kleef¹, Mesut Savas^{2

3}, Maurice Michel^{4

5}, Cyrielle Caussy^{6

7}, Jesse Pustjens¹, Adriaan G Holleboom^{8

9}, Elisabeth F C van Rossum^{2

3}, Harry L A Janssen^{1

10}, Jörn M Schattenberg^{4

5}, Willem P Brouwer¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
² Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
³ Obesity Center CGG, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
⁴ Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany.
⁵ Medical Faculty, Saarland University, Saarbrücken, Germany.
⁶ Hospices Civils de Lyon, Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud Pierre-Bénite, France.
⁷ Univ Lyon, CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1 Pierre-Bénite, France.
⁸ Department of Vascular Medicine, Amsterdam UMC, Amsterdam, the Netherlands.
⁹ Amsterdam Gastroenterology Endocrinology and Metabolism Institute, Amsterdam UMC, Amsterdam, the Netherlands.
¹⁰ Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Canada.

Abstract

Background and aims: Weight loss of ≥3%-10% is recommended in metabolic dysfunction-associated steatotic liver disease (MASLD) management, according to current guidelines. We investigated the associations between weight change and impaired metabolic liver health and focused on associations beyond these recommendations.

Methods: Adults from the National Health and Nutrition Examination Survey 2017-2020, with data on 1-year weight history, controlled attenuation parameter and/or liver stiffness measurement (LSM) were selected. Exclusion criteria were age ≥80 years, body mass index <18.5 kg/m², excessive alcohol and viral hepatitis. Impaired metabolic liver health included MASLD (controlled attenuation parameter ≥275 dB/m with ≥1 cardiometabolic riskfactor), at-risk metabolic dysfunction-associated steatohepatitis (MASH) (FibroScan aspartate aminotransferase score ≥0.35) and LSM ≥8 kPa. Multivariate logistic regression models were adjusted for demographics and prior weight.

Results: We included 6802 individuals (aged 48 years [33-62], 48.9% male). MASLD was present in 42.2%, at-risk MASH in 6.5% and LSM ≥8 kPa in 9.1%. Over 1 year, 29% gained and 28% lost ≥3% weight. Compared to stable weight, weight gain ≥3% was associated with increased MASLD prevalence (adjusted odds ratio (aOR):1.78; 95% confidence interval (CI): 1.48-1.95), at-risk MASH (aOR: 1.78; 95% CI: 1.39-2.29) and LSM ≥8 kPa (aOR:1.48; 95%CI:1.19-1.84); whilst weight loss ≥ 3% was associated with reduced MASLD prevalence (aOR: 0.54; 95% CI: 0.47-0.62), at-risk MASH (aOR: 0.72; 95% CI: 0.55-0.94) and LSM ≥8 kPa (aOR: 0.62; 95% CI: 0.49-0.78). Results were consistent when weight loss was further categorized or when assessed as continuous variable without evidence for nonlinearity.

Conclusion: The prevalence of impaired metabolic liver health decreased with weight loss. Greater reported weight loss was associated with lower observed risks. Hence, we should recommend losing weight beyond the currently recommended targets to further reduce the risk of advanced liver disease.

Keywords: Epidemiology; Fibrosis; General Population; Liver Health; Liver Stiffness; MASH; MASLD; Obesity; Weight Change; Weight Loss.