Clinical Features

Patients with NAFLD are generally asymptomatic although may have abdominal discomfort and hepatomegaly. Clinical examination may reveal signs of portal hypertension such as splenomegaly or ascites if cirrhosis is present. Children may have acanthosis nigricans reflecting underlying insulin resistance.

Liver enzymes may be normal in up to 78% of patients including those with cirrhosis, and thus are insensitive for both the detection of NAFLD and the exclusion of advanced liver disease (3). When present, liver enzyme elevations are generally modest and restricted to alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST). Elevations of ALT and AST greater than five times the upper limit of normal are uncommon and should prompt investigation for an alternative cause. A ratio of AST/ALT > 1 may signify advanced fibrosis (36). Iron studies are also frequently elevated with elevated ferritin observed in 20% to 50% of patients and raised transferrin saturation in 5% to 10% of cases (2). This is presumably secondary to hepatic inflammation or low-grade systemic inflammation that may accompany the metabolic syndrome.

Imaging studies such as ultrasound, computed tomography and magnetic resonance imaging can be used to confirm the diagnosis of NAFLD and are accurate for detecting moderate to severe hepatic steatosis. The sensitivity and specificity of ultrasound for detecting >33% steatosis is between 60% to 94% and 88% to 95% respectively, although falls with increasing BMI to 49% and 75%, respectively, among morbidly obese individuals (37). Thus mild steatosis is difficult to exclude by ultrasound, particularly in the setting of obesity.

Localized proton magnetic resonance spectroscopy is able to accurately quantify hepatic triglyceride content in the liver whereas ultrasound, computed tomography and magnetic resonance are semi-quantitative at best (38). However, no imaging modality is able to differentiate between the histological subtypes of relatively benign non-alcoholic hepatic steatosis or more aggressive NASH. Nor is imaging able to stage the degree of liver fibrosis (39).

Liver biopsy is able to stage the disease and thus is valuable for prognostic reasons. In addition, histological evaluation can be useful to exclude other liver disease, particularly in the setting of potential concomitant drug hepatotoxicity, elevated iron studies or positive auto-antibodies (2,40). Importantly, monitoring disease progression or response to therapy requires a liver biopsy as aminotransaminase levels improve over time regardless of whether hepatic fibrosis progresses or improves (33). The potential benefits of liver biopsy must be weighed against the small risk of complications including pain, bleeding and rarely death. The decision to pursue biopsy needs to be discussed and individualized with each patient.

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