Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay

Mayo, Marlyn J., Parkes, Julie, Adams-Huet, Beverley, Combes, Burton, Mills, A. S., Markin, Rodney S., Rubin, Raphael, Wheeler, Donald, Contos, Melissa, West, A. B., Saldana, Sandra, Getachew, Yonas, Butsch, Robert, Luketic, Velimir, Peters, Marion, Di Bisceglie, Adrian, Bass, Nathan, Lake, John, Boyer, Thomas, Martinez, Enrique, Boyer, James, Garcia-Tsao, Guadalupe, Barnes, David and Rosenberg, William M. (2008) Prediction of clinical outcomes in primary biliary cirrhosis by serum enhanced liver fibrosis assay. Hepatology, 48 (5), 1549-1557. (doi:10.1002/hep.22517). (PMID:18846542)

Abstract

Primary biliary cirrhosis (PBC) is sometimes diagnosed based on a positive antimitochondrial antibody in the appropriate clinical setting without a liver biopsy. Although a liver biopsy can assess the extent of liver fibrosis and provide prognostic information, serum fibrosis markers avoid biopsy complications and sampling error and provide results as a continuous variable, which may be more precise than categorical histological stages. The current study was undertaken to evaluate serum fibrosis markers as predictors of clinical progression in a large cohort of PBC patients. Serial liver biopsy specimens and serum samples were collected every 2 years in 161 PBC subjects for a median of 7.3 years. Clinical progression was defined as development of one or more of the following events: varices, variceal bleed, ascites, encephalopathy, liver transplantation, or liver-related death. Serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and procollagen III aminopeptide were measured and entered into the previously validated enhanced liver fibrosis (ELF) algorithm. The ability of ELF, histological fibrosis, bilirubin, Model for End-Stage Liver Disease (MELD), and Mayo Risk Score to differentiate between individuals who would experience a clinical event from those who would not was evaluated at different time points. Event-free survival was significantly lower in those with high baseline ELF. Each 1-point increase in ELF was associated with a threefold increase in future complications. The prognostic performance of all tests was similar when performed close to the time of the first event. However, at earlier times in the disease process (4 and 6 years before the first event), the prognostic performance of ELF was significantly better than MELD or Mayo R score. Conclusion: The ELF algorithm is a highly accurate noninvasive measure of PBC disease severity that provides useful long-term prognostic information. (HEPATOLOGY 2008;48:1549-1557.)

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Contributors

Author: Julie Parkes

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