Genetic Predisposition Links Lean and Obese MASLD to Similar Fibrosis Risk: Study

Written By : Dr. Shravani Dali Published On 2025-11-14T20:00:29+05:30 | Updated On 14 Nov 2025 8:00 PM IST

A new study published in Alimentary Pharmacology & Therapeutics has revealed that lean individuals with metabolic dysfunction–associated steatotic liver disease (MASLD) face a comparable risk of developing significant liver fibrosis as overweight or obese patients. The research highlights that genetic factors, rather than body weight alone, may play a critical role in determining fibrosis risk in MASLD. These findings challenge the traditional assumption that fibrosis severity is primarily linked to obesity and metabolic load, suggesting that lean MASLD should not be underestimated in clinical assessment.

The investigators conducted a detailed analysis of patients with MASLD across varying body mass index (BMI) categories, assessing fibrosis prevalence in relation to genetic risk scores (GRS). Results showed that individuals with higher GRS values demonstrated markedly higher rates of significant fibrosis compared to those with lower GRS. Importantly, the prevalence of fibrosis was consistent between lean and non-lean groups, underscoring that genetic susceptibility may override the influence of adiposity in fibrosis progression. This pattern suggests that genetic predisposition can serve as a more powerful predictor of disease advancement than traditional metabolic risk factors.

The study emphasizes the importance of integrating genetic profiling into MASLD evaluation to better stratify patients’ fibrosis risk. Routine liver monitoring and fibrosis assessment should extend to lean individuals with metabolic dysfunction, particularly those carrying higher genetic risk variants. By recognizing the genetic underpinnings of fibrosis progression, clinicians can implement more personalized management strategies, targeting those at greater risk regardless of body weight.

Keywords: Metabolic dysfunction–associated steatotic liver disease, MASLD, liver fibrosis, genetic risk score, lean MASLD, obesity, metabolic dysfunction, Alimentary Pharmacology & Therapeutics.

Reference (APA style):

Cozlea, A., Vonghia, L., Houben, T., et al. (2025). Genetic predisposition links lean and obese MASLD to similar fibrosis risk. Alimentary Pharmacology & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/41147688/

Metabolic dysfunction–associated steatotic liver diseaseMASLDliver fibrosisgenetic risk scorelean MASLDobesitymetabolic dysfunctionAlimentary Pharmacology & Therapeutics.

Source : Alimentary Pharmacology & Therapeutics

Dr. Shravani Dali

Dr. Shravani Dali has completed her BDS from Pravara institute of medical sciences, loni. Following which she extensively worked in the healthcare sector for 2+ years. She has been actively involved in writing blogs in field of health and wellness. Currently she is pursuing her Masters of public health-health administration from Tata institute of social sciences. She can be contacted at editorial@medicaldialogues.in.