Assessment of Liver Fibrosis: Can Serum Become the Sample of Choice?

Chronic hepatitis is a relatively common problem; worldwide, an estimated 350 million individuals are chronically infected with hepatitis B (HBV), 170 million are chronically infected with hepatitis C (HCV), and nonalcoholic fatty liver disease is predicted to reach epidemic proportions with the rapidly increasing prevalence of obesity and type 2 diabetes mellitus. Chronic hepatitis causes relatively minor symptoms by itself, but it may progress to cirrhosis (the 10th leading cause of death in the United States) and hepatocellular carcinoma (the 3rd leading cause of cancer death world wide). Although exact figures are lacking, it is estimated that ∼20%–30% of persons with chronic HBV or HCV will develop cirrhosis if untreated; however, successful treatment of HBV and HCV seems to prevent progression to cirrhosis and reduces the likelihood of or prevents development of hepatocellular carcinoma (1)(2).There are two major components to chronic hepatitis: necroinflammatory activity and fibrosis. The laboratory finding most correlated with activity is release of hepatocyte cytoplasmic enzymes such as aspartate and alanine aminotransferases. Unfortunately, the feature that best correlates with likelihood of developing cirrhosis is fibrosis; there is no correlation between aminotransferase activities and fibrosis.Liver biopsy has been considered the gold standard for evaluation of extent of fibrosis, but it has considerable limitations. Biopsy is an expensive, invasive procedure with a considerable risk of complications (particularly bleeding) and a small chance (<1:1000) of death. Chronic hepatitis does not affect the liver uniformly; the extent of fibrosis may vary from one part of the liver to another, and liver biopsy samples only 1:50 000th of the mass of the liver. Even with adequate-sized biopsies, cirrhosis may be missed in 15%–30% of liver biopsies. Moreover, inter- and intraobserver agreement in liver biopsy interpretation are less than optimal, although agreement is generally high for the more …