Chapter 43

• Nonalcoholic fatty liver disease (NAFLD) is an overarching concept that includes simple steatosis and nonalcoholic steatohepatitis (NASH).
• NAFLD is commonly associated with the metabolic syndrome, obesity, diabetes, and hyperlipidemia; 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, and magnetic resonance imaging are useful for the detection.
• Liver biopsy is currently required to distinguish NASH from NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, the hepatocellular accumulation of triglycerides in the absence of significant alcohol consumption. Simple steatosis connotes fat accumulation in the absence of inflammation in the liver. By contrast, nonalcoholic steatohepatitis (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 is also commonly employed to connote simple steatosis.

Whereas the histopathology of NAFLD and NASH is similar to that of alcohol-related liver disease, the etiology is quite distinct. An abundance of basic and clinical research has 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, diabetes, and hyperlipidemia. Although early studies suggested NAFLD to be a benign condition, it is now apparent that NAFLD is a major cause of liver-related morbidity and mortality.

### 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 is considered to be in the range of 20% in the United States and between 11.5% and 46% of the general population. By contrast, the prevalence of NASH is much lower, and in the range of 2% to 3%. As a result, the prevalences of NAFLD and NASH easily exceed chronic hepatitis C (HCV) infection, which afflicts 1.8% of the U.S. population. Recently, a common polymorphism in the gene encoding patatin-like phospholipase-3 (PNPLA3) (synonym adiponutrin) was shown to be strongly associated with NAFLD and its histopathologic severity.

Population-based studies have revealed 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 over time in parallel to the epidemic of obesity and diabetes. Of particular concern is that NAFLD is increasing in the pediatric population, with prevalences estimated at around 3% of children and 20–50% of obese children.

Argo CK, Caldwell SH. ...

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