Prediction of Clinical Outcomes in Primary Biliary Cirrhosis by Serum Enhanced Liver Fibrosis Assay

Authors

Marlyn J. Mayo, University of Texas Southwestern Medical Center, Dallas
Julie Parkes, Applied Epidemiology Group and Liver Group, University of Southampton, Southampton, UK
Beverley Adams-Huet, University of Texas Southwestern Medical Center, Dallas
Burton Combes, University of Texas Southwestern Medical Center at Dallas
A. Mills, Virginia Commonwealth University Medical Center, Richmond
Rodney Markin, University of Nebraska Medical CenterFollow
Raphael Rubin, Thomas Jefferson University, Philadelphia
Donald Wheeler, University of South Florida, Tampa
Melissa Contos, Virginia Commonwealth University Medical Center, Richmond
A B. West, Yale University, New Haven, CT
Sandra Saldana, Loma Linda University, Loma Linda, CA
Yonas Getachew, University of Texas Southwestern Medical Center at Dallas
Robert Butsch, University of Texas Southwestern Medical Center at Dallas
Velimir Luketic, Virginia Commonwealth University
Adrian Di Bisceglie, St. Louis University School of Medicine, St. Louis, MO
Nathan Bass, St. Louis University School of Medicine, St. Louis, MO
John Lake, University of Minnesota, Minneapolis, MN
Thomas Boyer, Liver Research Institute, Tucson, AZ
Enrique Martinez, The Liver Center, Atlanta, GA
James Boyer, Yale University, New Haven, CT
Guadalupe Garcia-Tsao, Yale University School of Medicine and Veterans Administration CT Healthcare System, Department of Internal Medicine, Section of Digestive Diseases
David Barnes, The Cleveland Clinic Foundation, Cleveland, OH
William Rosenberg, University of Southampton, Southampton, UK

Date of this Version

2008

Citation

HEPATOLOGY, November 2008;

DOI 10.1002

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 PBCpatients. 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.)