Nonalcoholic Fatty Liver Disease in Lean Individuals

Nonalcoholic fatty liver disease in lean individuals represents an emerging clinical phenotype characterised by hepatic steatosis despite a body mass index within normal ranges and minimal alcohol intake. Prevalence estimates vary from around 5 per cent of the general population up to 20 per cent of those with fatty liver, with geographic and ethnic differences linked to dietary patterns, genetic predispositions and lifestyle. Pathogenic mechanisms include insulin resistance, dysregulated lipid handling, visceral adiposity and gut microbiota alterations alongside genetic variants such as those in the PNPLA3 gene. Histologically, lean individuals may present with inflammation and fibrosis grades comparable to or exceeding those in obese patients. Clinically, this subgroup carries similar risks of cardiovascular disease, type 2 diabetes and progressive liver injury, underscoring the need for early detection, targeted lifestyle intervention and exploration of emerging pharmacotherapies to reduce visceral fat and mitigate long-term complications.

Research from Nature Portfolio

Large-scale prospective cohort work has demonstrated that among non-obese persons with fatty liver, a reduction in waist-to-hip ratio exceeding 5 per cent is associated with a significant decrease in the incidence of chronic kidney disease over a decade of follow-up. This finding emphasises the importance of central fat distribution as a modifiable risk factor in lean fatty liver disease and supports routine monitoring of waist and hip circumferences alongside conventional metabolic assessments.

Nonalcoholic Fatty Liver Disease in Lean Individuals publication trend

The graph below shows the total number of articles in nonalcoholic fatty liver disease in lean individuals across all publications each year (not limited to Nature Index journals).

Technical terms

Nonalcoholic Fatty Liver Disease (NAFLD): Accumulation of fat in hepatocytes in the absence of significant alcohol consumption.

Lean NAFLD: NAFLD occurring in individuals with a body mass index below obesity thresholds, typically < 25 kg/m².

Nonalcoholic Steatohepatitis (NASH): An inflammatory stage of NAFLD marked by hepatocyte injury and varying degrees of fibrosis.

Visceral Adiposity: Fat deposition around internal organs that contributes to metabolic risk independently of total body weight.

Waist-to-Hip Ratio (WHR): A measure of central fat distribution calculated by dividing waist circumference by hip circumference.

Fibrosis: Deposition of extracellular matrix in the liver, indicating chronic injury and predicting adverse outcomes.

References

1. Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients. Journal of Clinical Medicine (2018).
2. The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals. PLOS ONE (2015).
3. Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges. Biomedicines (2021).
4. Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease. Gut and Liver (2021).
5. Nutrition and Nonalcoholic Fatty Liver Disease: The Significance of Cholesterol. International Journal of Hepatology (2012).
6. Decrease in waist-to-hip ratio reduced the development of chronic kidney disease in non-obese non-alcoholic fatty liver disease. Scientific Reports (2020).
7. What Is New in Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals: From Bench to Bedside. Journal of Clinical Medicine (2024).