Recent advances in lean NAFLD - 31/08/22

Doi : 10.1016/j.biopha.2022.113331

Ruohui Xu ^a, Jiashu Pan ^a,^b, Wenjun Zhou ^a, Guang Ji ^a,^⁎ , Yanqi Dang ^a,^⁎
^a Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
^b Department of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

^⁎Corresponding authors.

Abstract

As the predominant type of chronic liver disease, the growing prevalence of nonalcoholic fatty liver disease (NAFLD) has become a concern worldwide. Although obesity plays the most pivotal role in NAFLD, approximately 10–20% of individuals with NAFLD who are not overweight or obese (BMI < 25 kg/m2, or BMI < 23 kg/m2 in Asians) have “lean NAFLD.” Lean individuals with NAFLD have a lower prevalence of diabetes, hypertension, hypertriglyceridemia, central obesity, and metabolic syndrome than nonlean individuals with NAFLD, but higher fibrosis scores and rates of cardiovascular morbidity and all-cause mortality in advanced stages. The pathophysiological mechanisms of lean NAFLD remain poorly understood. Studies have shown that lean NAFLD is more correlated with factors such as environmental, genetic susceptibility, and epigenetic regulation. This review will examine the way in which the research progress and characteristic of lean NAFLD, and explore the function of epigenetic modification to provide the basis for the clinical treatment and diagnosis of lean NAFLD.

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Graphical Abstract

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Highlights

•	Approximately 10–20% of individuals with NAFLD have “lean NAFLD.”
•	Lean individuals with NAFLD have a lower prevalence of diabetes, hypertension, hypertriglyceridemia, obesity, and metabolic syndrome, but higher fibrosis scores and rates of cardiovascular morbidity and all-cause mortality in advanced stages.
•	Lean NAFLD is categorized into two broad subtypes based on epidemiology, natural history, and prognosis.
•	The progression of lean NAFLD is affected by multiple epigenetic mechanisms.
•	The development of an improved non-invasive assessment and animal models of lean NAFLD are urgent.