Editorial: Comparable Hepatic Fibrosis Risk Demands Equal Vigilance in Lean and Non‐Lean Patients With Metabolic Dysfunction‐Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease worldwide. Although commonly linked to obesity, MASLD also affects individuals with normal body-mass index (BMI) (‘lean MASLD’), accounting for nearly 20% of all patients with MASLD and about 5% of the general population [1, 2]. Patients with lean MASLD are metabolically unhealthy and show visceral adiposity and metabolic abnormalities, such as insulin resistance, dyslipidemia, and hypertension. Once considered a milder phenotype, lean MASLD is now recognised as clinically significant, with emerging data indicating a comparable or even increased risk of hepatic fibrosis progression, liver-related diseases, and mortality compared with non-lean MASLD [3]. Tesfai et al. addressed this knowledge gap by designing a study to compare the hepatic fibrosis risk and genetic susceptibility between patients with lean and non-lean MASLD in a prospectively enrolled age and/or sex-matched cohort [4]. Using liver fibrosis assessment, Tesfai et al. analysed the key steatotic liver disease variants PNPLA3 I148M, TM6SF2 E167K, and the protective HSD17B13 allele to construct a genetic risk score (GRS). Patients with lean and non-lean MASLD had a similar prevalence of significant fibrosis (27.3% vs. 31.1%, p = 0.653); however, a higher three-variant GRS conferred a greater fibrosis risk, irrespective of BMI (36.5% vs. 25.2%, p = 0.043). These findings demonstrate that genetic predisposition drives the risk of hepatic fibrosis independent of BMI and that lean MASLD is far from benign. Clinically, these results emphasise the need for routine fibrosis risk assessment in all patients with MASLD, including those with normal BMI. The FIB-4 index should be used as a first-line screening tool, with subsequent liver stiffness measurements, for individuals with indeterminate or high FIB-4 values, in all metabolically at-risk individuals. Furthermore, a body composition analyser is a valuable tool for assessing both skeletal muscle mass and body fat, thereby identifying patients with sarcopenia and lean MASLD who tend to have a poorer prognosis [5]. Appropriate lifestyle modifications are essential for both lean and non-lean MASLD. Emphasis has been placed on physical activity [6] and dietary composition to improve insulin sensitivity and hepatic steatosis. A Mediterranean-style diet is particularly beneficial even without significant weight loss; it can reduce hepatic steatosis and ameliorate insulin resistance in patients with MASLD [7]. Managing comorbidities such as type 2 diabetes and dyslipidemia is equally crucial. Although racial differences in PNPLA3 expression must be considered [8], genetic risk profiling may become a valuable tool for identifying high-risk individuals and personalising their management in the future. Consequently, patients carrying high-risk variants should be prioritised for aggressive monitoring or novel therapies. Finally, clinicians should remain vigilant regarding extrahepatic complications of MASLD across all BMI categories. Lean individuals with MASLD may also be predisposed to lifestyle-related extrahepatic comorbidities that affect longevity and quality of life [9, 10]. These findings highlight that MASLD is a systemic metabolic disorder rather than merely a liver disease, even in the absence of obesity. Lean MASLD should not be overlooked and deserves meticulous screening, risk stratification, and proactive management, similar to non-lean MASLD, to mitigate the progression of hepatic fibrosis and improve long-term outcomes. Shinya Yokoyama: writing – review and editing, writing – original draft, conceptualization. Takanori Ito: writing – review and editing. S.Y.: None to declare. T.I.: Takanori Ito received honoraria from Chugai Pharmaceutical, Eisai, AstraZeneca, and Ono Pharmaceutical/BMS. This article is linked to Tesfai et al. papers. To view these articles, https://doi.org/10.1111/apt.70433 and https://doi.org/10.1111/apt.70460. The data that support the findings of this study are available from the corresponding author upon reasonable request.