Nonalcoholic Fatty Liver Disease

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


April 16, 2003

In This Article


Imaging studies ( Table 5 ) such as ultrasound (sonography) may provide the first indication that patients have hepatic steatosis.[23]

Sonography is the most commonly used modality for the diagnosis of a fatty liver. The sonographic findings of fatty liver include increased echogenicity of the liver parenchyma and blurring of the vascular margins (Figure 3).

Figure 3.

A sonogram of a fatty liver showing increased echotexture compared with the adjacent kidney (bright liver). This is not a specific finding for NAFLD.

Sonography is a sensitive but relatively nonspecific tool for the diagnosis of fatty liver. A CT scan is more specific for the diagnosis of fatty liver and has comparable sensitivity. However, CT scan is more costly than sonography. The presence of a fatty liver decreases the hepatic image intensity (ie, makes it appear darker on CT scan). When the spleen is more than 10 Hounsfield units brighter than the liver, a fatty liver can be diagnosed with confidence. A fatty liver shows enhancement of its image after intravenous contrast administration, but this is less marked than the spleen. When the spleen is more than 20 Hounsfield units brighter than the liver in a postcontrast CT scan, a fatty liver can be diagnosed. A fatty liver may also be diagnosed with relatively high sensitivity and specificity by gradient-echo MR pulse sequences. None of these imaging modalities, however, can distinguish a fatty liver from steatohepatitis, as confirmed by a recent study.[24] These modalities are also poor in terms of assessing the stage of liver fibrosis. Therefore, imaging studies may help with diagnosing fatty infiltration of the liver, but they do not help in distinguishing between fatty liver, steatohepatitis, and steatohepatitis with fibrosis.

Liver biopsy remains the gold standard for the assessment of liver histology and is therefore a key test used to establish the diagnosis of NAFLD. Before undergoing the risk of liver biopsy, however, it must first be discussed with the patient whether the results will provide benefit. In the absence of effective therapy, one may argue that a liver biopsy will not change the management of the patient and is therefore not indicated in routine clinical practice. Until an effective therapy exists for NAFLD, the decision of whether to perform a liver biopsy will remain controversial. However, at this time, those patients who are likely to be enrolled in therapeutic trials for steatohepatitis should be characterized by liver biopsy prior to enrollment. Also, a liver biopsy is essential if there is uncertainty concerning the diagnosis. Finally, a liver biopsy represents the only accurate way to stage fibrosis in the liver. Thus, the decision of whether to perform a liver biopsy in routine practice should be guided by the information that will be provided by the biopsy, and whether that information will be used to make management decisions.

The microscopic features of NAFLD may be indistinguishable from those of alcoholic fatty liver disease. As in alcoholic liver disease, the major histologic feature of NAFLD is predominantly macrovesicular hepatic steatosis ( Table 6 ).

Other findings include hepatocellular ballooning, Mallory bodies (Figure 4), pericentral perisinusoidal fibrosis (Figure 5), and lobular and portal inflammation. Glycogen nuclei are often seen in patients with NAFLD, but are not a specific finding.

Figure 4.

Mallory body is shown within a ballooned hepatocyte.

Figure 5.

Pericellular fibrosis is shown (Masson's trichrome stain). The collagenous tissue (shown in blue) surrounds individual hepatocytes, producing a chicken-wire appearance.

Unlike other forms of chronic liver disease, no consensus currently exists regarding the grading and staging of NAFLD. The grade indicates the activity of the steatohepatic lesion, whereas the stage reflects the degree of fibrosis. Although the interobserver variability is relatively low in terms of diagnosing steatosis, cytologic ballooning, and perisinusoidal fibrosis, there is considerable variability with regard to the assessment of inflammatory changes. A scoring system has been proposed by Brunt and colleagues ( Table 7 )[25] in which individual parameters indicative of necroinflammatory activity (eg, cytologic ballooning, steatosis, and inflammation) are scored separately and then a composite score is derived to indicate the grade of steatohepatitis. This approach also includes a staging system to assess hepatic fibrosis, which includes an assessment of perisinusoidal fibrosis, portal fibrosis, and bridging fibrosis.

Nonalcoholic steatohepatitis (NASH)/NAFLD can progress to cirrhosis (Figure 6). Once cirrhosis develops, the amount of steatosis decreases, and may even disappear completely. Additionally, the amount of cytologic ballooning may decrease.

Figure 6.

Steatohepatitis with cirrhosis. A nodule of liver tissue is circumscribed by scar tissue.
From Sanyal AJ. Nonalcoholic steatohepatitis. Clinical Perspectives in Gastroenterology. 2000;130(May/June). Copyright 2000; republished with permission from Elsevier.

As the lobular architecture becomes distorted by the remodeling of the liver during transition to cirrhosis, it becomes increasingly difficult to assess pericentral, perisinusoidal fibrosis. In other words, the key histologic features of steatohepatitis either disappear or become difficult to assess once cirrhosis develops. Many such cases are labeled as cryptogenic cirrhosis. In these settings, the diagnosis can only be determined from the clinical profile of the patient and the presence of risk factors for NAFLD.