Individuals with non-alcoholic fatty liver disease (NAFLD) who lack classical risk factors also have the ability to develop nonalcoholic steatohepatitis (NASH) and progression to more advanced liver disease. The pathophysiology and risk factors for the development of NAFLD in non-obese persons are not fully understood but seem to be closely related to insulin resistance, atherogenic dyslipidaemia and alterations in body composition, with some patients harbouring predisposing genetic polymorphisms. In normal-weight individuals, also called ‘lean’, there is limited potential for effective lifestyle change in disease management. Additionally, biological mechanisms underlying the development of NASH in non-obese individuals may reveal novel targets for intervention. In this review, the authors discuss the clinical, histological and genetic features and risk factors for non-obese NAFLD and highlight gaps in knowledge and areas for future research.
- hepatic fibrosis
- lipid metabolism
- nonalcoholic steatohepatitis
- chronic liver disease
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Contributors MP: contributed to the planning and drafting of the work. JW: contributed to conceptualising, revising and supervising the work.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests JW has paid consulting activities with Astra Zeneca and has received research support from Janssen, Genfit, Intercept, Galectin, Gilead, Zydus, Conatus, and Shire.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.