NASH in lean individuals
Open accessAbstract
in Asian subjects, the so-called "lean" NAFLD. This sub-phenotype of NAFLD patients has been described across populations of different ethnicity, particularly in Asia, but it can be diagnosed in 10 to 20% of nonobese Americans and Caucasians. Pathophysiological mechanisms underpinning the "lean" phenotype are not completely understood, but they may include a more dysfunctional fat (visceral obesity, differences in adipocyte differentiation and altered lipid turnover), altered body composition (decreased muscle mass), a genetic background, not limited to patatin-like phospholipase domain-containing protein 3 (PNPLA3) C > G polymorphisms, epigenetic changes occurring early in life and a different pattern of gut microbiota. Lean subjects with NAFLD have milder features of the metabolic syndrome when compared with obese patients. Nonetheless they have a higher prevalence of metabolic alterations (e.g., dyslipidemia, arterial hypertension, insulin resistance, and diabetes) compared with healthy controls. Data on histological severity are controversial, but they can develop the full spectrum of liver disease associated with nonalcoholic steatohepatitis NASH. Since lean NAFLD usually present with less obesity-related comorbidities, it is commonly believed that this group would follow a relatively benign clinical course but recent data challenge this concept. Here, the authors describe the current knowledge about NAFLD in lean individuals and highlight the unanswered questions and gaps in the field.
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Normal-weight individuals with MASLD have a higher prevalence of metabolic alterations including insulin resistance, greater visceral obesity, and decreased muscle mass compared to normal-weight controls.
“Normal-weight individuals with MASLD have a higher prevalence of metabolic alterations including insulin resistance, greater visceral obesity, and decreased muscle mass compared to normal-weight controls. 331,332”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [331]
In “Insulin Resistance and Fat Distribution” (page unavailable), the review says lean NAFLD patients are insulin resistant compared with healthy controls. It also links the likely metabolically obese normal-weight phenotype to greater visceral fat, but does not directly compare visceral fat in lean NAFLD patients and normal-weight controls. The same section discusses sarcopenia as a risk factor for NAFLD, not decreased muscle mass in lean patients relative to controls. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA few small observational studies have indicated that dietary fructose and sugar-sweetened beverage consumption is higher in individuals with MASLD and no obesity.
“A few small observational studies have indicated that dietary fructose and sugar-sweetened beverage consumption is higher in individuals with MASLD and no obesity; 330,331”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [331]
The Genetic and Environmental Factors section reports that young nonobese subjects with NAFLD consumed more soft drinks and juices than healthy controls, and describes high fructose intake as a risk factor. It cites one such study, however, and does not establish from several small observational studies that dietary fructose intake itself was higher in this population. (LLM, conf=0.82)
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- Authors
- Younes, R., & Bugianesi, E.
- Affiliations
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Corresponding author
- Bugianesi, Elisabetta
- Venue
- Seminars in Liver Disease
- Publisher
- Georg Thieme Verlag KG
- Published
- 2019-01-17
- Volume
- 39
- Issue
- 01
- Pages
- 086-095
- ISSN
- 0272-8087 (ISSN-L)
- 1098-8971
- OpenAlex
- W2909142264
- Cited by
- 235
- References
- 65
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 50 · 2023: 42 · 2022: 44 · 2021: 31 · 2020: 34 · 2019: 9
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Seminars in Liver Disease (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Horizon 2020 Framework Program of the European Union (634413, 777377)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- lean NAFLD, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, gut microbiota, metabolic syndrome, insulin resistance, dyslipidemia, hypertension, diabetes mellitus, visceral obesity, adipogenesis, body composition, Asian populations
- MeSH terms
- Animals, Feeding Behavior, Female, Humans, Insulin Resistance, Male, Body Mass Index, Genetic Predisposition to Disease, Asian People, Adiposity, Ideal Body Weight, Non-alcoholic Fatty Liver Disease
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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