Nonalcoholic fatty liver disease

Sandra K. Erickson

doi:10.1194/jlr.r800089-jlr200

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximately 75-92% and in the pediatric population at approximately 13-14%. The progressive form of NAFLD, nonalcoholic steatohepatitis, is estimated at approximately 3-5%, with approximately 3-5% of these having progressed to cirrhosis. Thus, the numbers of individuals at risk for end-stage liver disease and development of primary liver cancer is large. NAFLD is an independent risk factor for cardiovascular disease, leads to increased all-cause mortality, and to increased liver-related mortality. This review focuses on recent advances in our understanding of the NAFLD disease spectrum, including etiology, diagnosis, treatment, and genetic and environmental risk factors and suggests future directions for research in this important area.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, worldwide
It is estimated that ?6 million individuals in the US general population have progressed to nonalcoholic steatohepatitis (NASH) and ?600,000 to NAFLD-related cirrhosis
NAFLD represents a spectrum of diseases ranging from “simple steatosis,” which is considered relatively benign, to NASH and NAFLD-associated cirrhosis and end-stage liver disease

Summary

ROLE OF GENETICS

A number of studies over the years have implicated genetic predisposition in NAFLD. For example, it was noted that NAFLD appears to have a familial component [27, 28]. As technical and financial constraints have eased, samples from populations with well-defined NAFLD have begun to be used for genome scans to discover gene variants that are more common in NAFLD patients than in a control population. Using this technique, a study from the Dallas group [37] identified ethnic differences in variants of a gene, PNPLA3, that are associated with different propensity to NAFLD and its progression. Knowledge of the identity of such chromosomal regions discovered in the mouse, and the genes harbored therein, can be translated to the human genome to define areas with high probability of relationship with human NAFLD and its progression

ROLE OF ENVIRONMENTAL FACTORS

ANIMAL MODELS

SUMMARY AND FUTURE DIRECTIONS