Abstract #1161642: Prevalence, Pathophysiology, and Management of Lean Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a pandemic with a prevalence of approximately 25% among adult population worldwide. The highest prevalence is observed in the Middle East (32%) and the lowest prevalence in Africa (13%). NAFLD is a spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). NASH is the aggressive form of NAFLD that can progress to cirrhosis and hepatocellular cancer. Although NAFLD is commonly associated with overweight and obesity, some NAFLD subjects are lean. The purpose of this review is to present an update on the prevalence, pathophysiology, and management of lean NAFLD subjects. A systematic search of literature was conducted using the search terms nonalcoholic fatty liver disease, lean, overweight, obesity, prevalence, pathophysiology, and management. A meta-analysis of 84 studies including 10,530,308 subjects showed that in the general population, 5.1% of the subjects have lean NAFLD and within the NAFLD population, 19.2% of the subjects are lean. The prevalence of lean NAFLD is higher in the middle-aged individuals of Asian countries. The underlying pathophysiology of lean NAFLD is not fully understood. Genetic and environmental factors may predispose to lean NAFLD. Several studies have reported that lean NAFLD subjects have a greater proportion of the variant PNPLA3 allele. Lean NAFLD subjects have the same comorbidities in comparison to non-lean NAFLD subjects (e.g., hypertension, type 2 diabetes, and dyslipidemia) and remain at risk for development of severe complications and high mortality. There are no specific treatments for lean NAFLD. While the first-line therapy of non-lean NAFLD is based on lifestyle intervention (diet and exercise) with a targeted weight loss of at least 7%, the relevance of diet and exercise in lean NAFLD is questionable. However, some lean NAFLD subjects may have visceral obesity not detected by body mass index (BMI) and can benefit from lifestyle intervention and weight loss. Also, exercise, independently of weight loss, may have a favorable impact. Lean NAFLD is a distinct entity with several metabolic abnormalities. It represents a significant portion of subjects with NAFLD even after using an ethnicity-specific BMI criterion (cutoffs of 25 in Caucasian and 23 in Asian subjects, respectively). The pathogenesis of lean NAFLD may be very different than non-lean NAFLD. In the absence of overweight or obesity (as defined by BMI), lean NAFLD may remain underrecognized. The treatment of lean NAFLD is a medical challenge. Lifestyle intervention and weight loss can be beneficial in some subjects.