Biopsy or Biomarkers: Is There a Gold Standard for Diagnosis of Liver Fibrosis?

Liver biopsy has long been the gold standard for the grading of hepatic inflammation and the staging of hepatic fibrosis, and has been used as the reference standard method in evaluations of plasma markers of liver disease. In the modern era with the use of ultrasound guidance, biopsy is an essentially safe procedure with a 0.3% rate of serious complications, such as postprocedure pain or bleeding. However, a liver biopsy samples only 1/50 000th of the liver parenchyma and is prone to sampling error, especially when there is a focal component to the liver disease. In addition, the quality of the liver biopsy and the experience of the pathologist are essential for correct grading and staging of liver disease.More recently, clinical investigators have been searching for noninvasive serum markers of fibrosis (1). These can be individual markers or a series of markers from which a fibrosis index can be derived. In either case, these marker tests must have the following characteristics: They must be reliable, accurate, reproducible, and easy to perform. In addition, they must reflect total mass of liver collagen and extracellular matrix (ECM) and be able to reflect both fibrogenesis and fibrosis regression. The ideal marker test would be able to accurately stage disease and also be sensitive to changes in fibrosis induced by therapy or the natural history of disease progression.In this issue of Clinical Chemistry , Poynard et al. (2) address one of the most important issues in this area: Is there a true gold standard for liver fibrosis? …