Fatty Liver Disease -- It's More Than Alcohol and Obesity

Heiner Wedemeyer, MD, Michael P. Manns, MD


July 23, 2003

In This Article

Diagnosis of NAFLD and NASH

An overview on the current state of the art of diagnosis of NAFLD was presented during the President's premeeting by Peter Ferenci[5] of Vienna, Austria. Hepatic fat accumulation can be demonstrated by ultrasonography, computerized tomography (CT), or magnetic resonance imaging; however, none of these methods provides information on the fine architecture of liver tissue or on the etiology of steatosis. Even hepatic fat accumulation, as diagnosed by an imaging technique, along with the finding of elevated aminotransferase levels are not sufficient to distinguish between fatty liver alone and NASH.[4] Thus, for the diagnosis of NASH to be established, a liver biopsy is still required and therefore remains the gold standard. Only information from biopsy allows grading and staging of the disease, as emphasized by pathologist Elizabeth Brunt[6] of the United States. This latter information is crucial for patient management because simple nonalcoholic fatty livers have a benign prognosis, whereas NASH can be progressive and lead to end-stage liver disease.

Typical histologic features of NASH primarily include macrovesicular steatosis, a mixed lobular inflammation, and hepatocellular ballooning. Frequent findings also include lipogranulomas in the lobules and acidophil bodies, as well as perisinusoidal fibrosis. Mallory bodies can be found in NASH in zone 3, whereas Mallory's hyaline in ballooned hepatocytes in zone 1 is more typical for diabetes- or amiodarone-induced steatohepatitis.[3] A scoring system to grade and stage NASH was proposed by Dr. Brunt[7] in 1999. Whereas grading not only takes the amount of fat accumulation into account but also considers ballooning and inflammation, staging from 1 to 4 is similar to scoring systems used for viral hepatitis[8,9] and distinguishes between perisinusoidal fibrosis, portal-based fibrosis, bridging fibrosis, and cirrhosis ( Table 1 ).

In the search for noninvasive methods of grading NASH, a Turkish group from Elazig explored whether calibrated CT might substitute for liver biopsies.[10] Data from 19 patients with histologically proven NASH who underwent CT were presented, and, interestingly, a linear correlation between CT scan density and histopathologic grade (r:-0.70) and stage (r:-0.51) was noted. Although these data must be confirmed in larger series, noninvasive grading and staging of NASH may be possible in the near future.

Currently, a liver biopsy is still required to confirm the diagnosis of NASH, as was demonstrated in a study from England presented during these meeting proceedings, in which 41 of 82 patients with NAFLD showed significant fibrosis on biopsy.[11] However, in contrast to the requirement of biopsies for primary diagnosis, for the majority of patients with NAFLD, there is now need for repeated liver biopsies after diagnosis has been confirmed, as highlighted by Dr. Ferenci.[5] Patient management and control of treatment success can be monitored with biochemical liver function tests. If the cause of the steatosis is abolished, results of imaging studies should show normal hepatic architecture over time.


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