NASH in Lean Individuals
Top Cited Papers
- 17 January 2019
- journal article
- review article
- Published by Georg Thieme Verlag KG in Seminars in Liver Disease
- Vol. 39 (01), 086-095
- https://doi.org/10.1055/s-0038-1677517
Abstract
Nonalcoholic fatty liver disease (NAFLD) is generally associated with obesity and the related comorbidities but it can also develop in subjects with a body mass index (BMI) within the ethnic-specific cutoff of 25 kg/m2 BMI in Caucasian and 23 kg/m2 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.Keywords
Funding Information
- Horizon 2020 Framework Program of the European Union (634413, 777377)
This publication has 60 references indexed in Scilit:
- In patients with non-alcoholic fatty liver disease, metabolically abnormal individuals are at a higher risk for mortality while metabolically normal individuals are notMetabolism, 2013
- Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty liver disease in Indian patients with normal body mass index: Do they differ from obese or overweight non-alcoholic fatty liver disease?Indian Journal of Endocrinology and Metabolism, 2013
- Associations of Visceral and Liver Fat With the Metabolic Syndrome Across the Spectrum of Obesity: The AGES‐Reykjavik StudyObesity, 2011
- Pioglitazone for Diabetes Prevention in Impaired Glucose ToleranceThe New England Journal of Medicine, 2011
- Visceral Adiposity IndexDiabetes Care, 2010
- Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver diseaseNature Genetics, 2008
- Intrauterine Growth Retardation, Insulin Resistance, and Nonalcoholic Fatty Liver Disease in ChildrenDiabetes Care, 2007
- Characteristics of metabolically obese normal-weight (MONW) subjectsApplied Physiology, Nutrition, and Metabolism, 2007
- Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptorBiochemical and Biophysical Research Communications, 2005
- Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndromeJournal of Hepatology, 2003