Pouneh S. Mofrad, MD, Arun J. Sanyal, MD


April 16, 2003

In This Article

Clinical Features

Like most chronic liver diseases, in NAFLD there is a long period during which an individual patient remains essentially asymptomatic. In asymptomatic individuals, the diagnosis is often made when a radiologic test performed for unrelated indications reveals evidence of a fatty liver. In other cases, a persistently elevated alanine aminotransferase (ALT) level leads to a work-up that yields the diagnosis. Another common modality of presentation is an elevated serum ALT level that is noted after a cholesterol-lowering drug is started. Frequently, baseline ALT levels are either already increased or are not available in such cases.

When symptoms occur, they are often relatively nonspecific (eg, fatigue and vague right upper quadrant discomfort; Table 4 ). Fatigue is the most common symptom associated with NAFLD. The degree of fatigue does not correlate with the histologic stage of liver disease nor the degree of hepatic synthetic dysfunction. In many instances, the presence of poorly controlled diabetes, hypothyroidism, or sleep apnea contributes to the fatigue, and these symptoms should be looked for and evaluated appropriately. Because hypertriglyceridemia and obesity are risk factors for not only NAFLD but also gallstones, many patients with NAFLD are also at risk of developing gallstones.[20,21] Patients with NAFLD may also present with symptomatic cholelithiasis; when an ultrasound is performed for these symptoms, a fatty liver may then be noted.

When the liver disease is more advanced, patients may develop symptoms indicative of severe liver disease. These symptoms include increasing fatigue, pruritus, edema, and jaundice. The development of variceal hemorrhage, ascites, or encephalopathy indicates the presence of cirrhosis.

In patients with NAFLD who do not have advanced liver disease, the most common sign on physical examination is hepatomegaly ( Table 4 ).[1,14] Some patients may have evidence of chronic liver disease such as palmar erythema, spider angioma, jaundice, and hepatic encephalopathy. As with other causes of advanced liver disease, patients who develop cirrhosis due to NAFLD may have stigmata of portal hypertension, such as ascites, anasarca, and varices. Some NAFLD patients, particularly children, may also have acanthosis nigricans, which has been associated with insulin-resistant states. NAFLD is also associated with several disorders characterized by abnormal body fat distribution (lipodystrophies). The body habitus of patients with suspected or proven NAFLD should be carefully evaluated for the presence of lipodystrophies. When suspected, such individuals should be referred for appropriate work-up for confirmation.

The presence of an elevated ALT level is often the first clue in the diagnosis of NAFLD. In the majority of patients, the serum ALT level is only increased by 1-4 times the upper limits of normal. AST levels may also be minimally elevated, but the AST:ALT ratio is usually < 1.[22] In individuals with cirrhosis, the AST:ALT ratio may exceed 1, but is rarely, if ever, > 2. This is a useful way to distinguish NAFLD from alcoholic liver disease, which is often associated with an AST: ALT ratio > 2. The degree of serum ALT elevation does not correlate with liver histology. ALT levels may also be normal in patients with NAFLD. A normal serum ALT does not exclude the possibility of underlying steatohepatitis or even cirrhosis.

Increased glucose levels and abnormal lipid profiles may also be found in these patients, given that individuals with diabetes mellitus and hyperlipidemia are at higher risk for developing NAFLD. In patients who develop cirrhosis, the serum albumin and prothrombin time may be abnormal. Serum bilirubin may also be elevated in patients with end-stage liver disease. Once portal hypertension and, therefore, hypersplenism occur, platelet counts may be decreased.