Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver - which generally follows a benign, non-progressive clinical course - to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of “pediatric” NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease.

Keywords: Non-alcoholic steatohepatitis; Children; Adolescents; Pathogenesis; Nonalcoholic fatty liver disease

Core tip: Much work on nonalcoholic fatty liver disease (NAFLD) has been done, but an accurate understanding of its mechanism remains unclear. Our objective was to examine the current literature to better understand the pathogenesis of NAFLD, thus showing how it evolved from the “two-hit theory” to a “multiple hit model”.