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September 24, 2003

Diagnosis of Nonalcoholic Fatty Liver Disease—Reply

Author Affiliations

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2003;290(12):1577. doi:10.1001/jama.290.12.1577-a

In Reply: We agree with Dr Yanai and Ms Morimoto that potential sampling error, risk of complications, and expense limit the widespread application of liver biopsy to stage fibrosis in patients with chronic liver diseases, including NAFLD. These inadequacies have motivated the search for noninvasive markers of hepatic fibrosis. No single test, whether invasive or noninvasive, can establish the extent of liver fibrosis. Indeed, the article by Dienstag,1 which Yanai and Morimoto cite, concludes that noninvasive markers of hepatic fibrosis are "insufficiently reliable to predict histological distinctions in populations with varying prevalence of fibrosis/cirrhosis or to provide anything more than broad qualitative distinctions, far short of the potential information in a liver biopsy." Similarly, Fontana and Lok2 concluded that individual serum fibrosis markers have "limited accuracy" and that panels of markers "require further validation." Marcellin et al3 reported that "serum markers for fibrosis are not reliable and need to be improved and validated. Liver biopsy provides the most accurate information on the stage of fibrosis." Based on this literature, we continue to believe that liver biopsy is the most accurate and widely accepted approach for staging hepatic fibrosis. This is also consistent with a recent review of the role of liver biopsy,4 which recommended liver biopsy for staging the severity of fibrosis in patients with almost all chronic liver diseases, including NAFLD. Nevertheless, there is no doubt that widespread application of this invasive procedure has considerable implications, which must be weighed against delaying or missing the diagnosis of significant underlying hepatic pathology. We suspect that this area will remain a subject of considerable debate until a safer and more accurate test to quantify liver fibrosis has been developed.

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