From the Guidelines
Lean Non-Alcoholic Fatty Liver Disease (NAFLD) or Non-Alcoholic Steatohepatitis (NASH) affects approximately 7-20% of individuals with NAFLD, occurring in individuals with a lean body habitus, and is associated with increased cardiovascular, liver, and all-cause mortality. The epidemiology of Lean NAFLD/NASH is characterized by a distinct pathophysiological mechanism, including genetic predisposition, altered gut microbiota, sarcopenia, and dysfunctional adipose tissue, which explains why these individuals develop liver fat despite normal BMI 1. Key aspects of Lean NAFLD/NASH management include:
- Lifestyle modifications with emphasis on regular physical activity and a Mediterranean diet pattern rich in unsaturated fats, fruits, vegetables, and whole grains
- Pharmacotherapy options, such as vitamin E, pioglitazone, and GLP-1 receptor agonists like semaglutide, for selected cases
- Regular monitoring with liver enzymes every 3-6 months and non-invasive fibrosis assessment annually
- Consideration of MASH-targeted treatment with resmetirom for adults with non-cirrhotic MASH and significant liver fibrosis, as recommended by the EASL-EASD-EASO clinical practice guidelines on the management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) 1. The most recent and highest quality study recommends a stepwise approach using blood-based scores, such as FIB-4, and imaging techniques, like transient elastography, to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes 1. It is essential to prioritize the management of Lean NAFLD/NASH, as these patients may have a higher risk of progressive liver disease compared to obese counterparts, making early identification and management crucial 1.
From the Research
Epidemiology of Lean MASLD
- The prevalence of lean Non-Alcoholic Fatty Liver Disease (NAFLD) varies widely, ranging from 3.8% to 34.1% 2.
- Lean patients account for approximately 10%-15% of the Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) population 2.
- The pathogenesis of lean MASLD is complex and not well understood, with associations found in genetic variants, epigenetic modifications, and adaptive metabolic response 2.
- Common risk factors for lean MASLD include metabolic syndrome, hypertension, and type 2 diabetes mellitus, but their prevalence varies based on the comparison group involving lean patients 2.
Management of Lean MASLD
- Lifestyle modifications, such as dietary changes and weight loss, can aid in reducing hepatic steatosis and improving cardiometabolic profiles in lean MASLD patients 2, 3.
- Some medications, such as pioglitazone and vitamin E, have shown efficacy in treating lean MASLD, but their use is limited and requires further research 3.
- Non-invasive tools, such as the Fibrosis-4 index, can be used to diagnose and monitor lean MASLD, and have been shown to outperform the NAFLD fibrosis score in lean patients 2.
Cardiovascular Morbidity and Mortality in Lean MASLD
- Lean MASLD patients exhibit a worse prognosis compared to non-lean MASLD patients, with a 50% increase in cardiovascular mortality odds 4.
- Lean MASLD patients have a 40% higher odds of all-cause mortality compared to non-lean MASLD patients 4.
- Despite a favorable cardiometabolic profile, lean individuals with MASLD face elevated cardiovascular mortality risk 4.
Global Epidemic of Metabolic Fatty Liver Disease
- The incidence and prevalence of MASLD are projected to increase significantly in the future as the population burden of cardiometabolic risk factors rises 5.
- MASLD is a potent risk factor for developing cardiovascular disease (CVD) and should be tackled by using a multi-disciplinary team with a holistic approach 5.
- The update in nomenclature from NAFLD to MASLD reduces the stigma associated with alcohol consumption and poor health choices, and shines a light on the crucial role of cardiometabolic risk factors in disease pathophysiology 5.