Lean NASH: distinctiveness and clinical implication

Abstract

Introduction: Non-alcoholic fatty liver (NAFL) in the absence of overweight and/or obesity, defined by the anthropometric parameter, body mass index (BMI), has been designated as 'lean NASH.' While maintaining a close pathophysiological link with metabolic syndrome (MS) and insulin resistance (IR), the presence of subtle alterations in measures of total body and regional adiposity not exceeding the designed cut-offs, are hallmarks of 'lean NASH.'

Material and methods: Available literature related to non-alcoholic steatohepatitis (NASH) in lean or non-obese individuals and its pathogenesis in general published in English language journals till the time of manuscript preparation were reviewed and critically analysed.

Analysis: Being a closely related but variant phenotype of NASH, its features metabolically resemble the well-characterized entity 'metabolically obese normal weight (MONW)' individuals. Apart from total body adiposity, distribution of fat in different body compartments has assumed greater pathophysiologic relevance in characterizing 'lean NASH'. Detection of NASH in stringently defined non-obese individuals, by both BMI and waist circumference indices, indicates existence of a subset of NASH in which fat compartmentalization at ectopic sites is not picked up by the anthropometric yardsticks used. Volume [Quantity] and biological behavior of the visceral and deep subcutaneous adipose tissues contribute to this variant of NASH in non-obese subjects. Genetic predisposition to IR and MS along with the environmental influences like childhood nutritional status, dietary composition and gut microbiome possibly play pathogenetic role.

Conclusion: The most important concern is in the principles of nomenclature within syndromes where clinical dissimilarities exist despite biological similarities. Till a uniformly acceptable pathophysiological and/or etiology-based classification emerges, the term "lean NASH" would continue to provide us an opportunity to ponder over and refine this subset of fatty liver in non-obese people and potentially significant liver disease.

Keywords: Adiposity; BMI; Lean; Obesity; Steatohepatitis; Waist circumference.