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  • Nonalcoholic fatty liver disease (NAFLD) is the term that represents a broad spectrum of disease ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and steatofibrosis.

  • NAFLD is commonly associated with the metabolic syndrome, obesity, type 2 diabetes, and dyslipidemia; 80% of patients with the metabolic syndrome have NAFLD.

  • Patients generally present without clinical symptoms but with mild transaminase elevations; NAFLD is the most common cause of increased serum transaminase levels.

  • NAFLD is a clinical diagnosis after exclusion of other causes of liver disease.

  • Ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are useful for the detection.

  • Liver biopsy is currently required to distinguish NASH from NAFLD.


NAFLD is characterized by hepatic steatosis, the hepatocellular accumulation of triglycerides in the absence of significant alcohol consumption. Simple steatosis, or bland steatosis, connotes fat accumulation in the absence of hepatic inflammation. By contrast, NASH indicates the presence of inflammation and fibrosis in association with hepatic steatosis. NAFLD is sometimes used as an overarching term that includes simple steatosis and NASH, but can include NASH-related cirrhosis and advanced disease, or nonalcoholic steatofibrosis.

Whereas the histopathology of NAFLD and NASH is similar to that of alcohol-related liver disease, the etiology is quite distinct. Significant data from basic and clinical research have demonstrated that the metabolic underpinnings of NAFLD are rooted in insulin resistance. Indeed, NAFLD is commonly associated with other manifestations of insulin resistance including obesity, essential hypertension, type 2 diabetes mellitus, low levels of high-density lipoprotein (HDL), hypertriglyceridemia, and less commonly polycystic ovarian disease, or hypothyroidism. Although early studies suggested it to be a benign condition, it is now apparent that NAFLD has become a major cause of liver-related morbidity and mortality.

A. Epidemiology

The absence of signs and symptoms, combined with a lack of sensitive and specific diagnostic tests, makes estimation of the prevalence of NAFLD difficult. Elevated liver enzymes are not sensitive for detecting NAFLD and there is no current consensus that histopathology is a gold standard for diagnosis. Although likely an underestimate for these reasons, the prevalence of NAFLD in the United States is considered to be in the range between 11% and 46% of the general population. The prevalence of NASH is significantly lower, in the range of 5–8%. As a result, the prevalences of NAFLD and NASH easily exceed chronic hepatitis C virus (HCV) infection, which afflicts 1.8% of the US population. A common polymorphism in the gene encoding patatin-like phospholipase-3 (PNPLA3) (synonym adiponutrin) is strongly associated with NAFLD (in some racial and ethnic groups) as well as histopathologic severity.

Population-based studies reveal that NAFLD is more common in men than women. It is more common in Hispanics compared with whites; and, more common in whites than blacks. It is assumed that the prevalence of NAFLD will increase ...

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