Prediction of clinical outcomes in primary biliary... : Hepatology (original) (raw)

Autoimmune, Cholestatic and Biliary Disease

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

Mayo, Marlyn J.1,22*; Parkes, Julie2; Adams-Huet, Beverley3; Combes, Burton4,22; Mills, A. S.5; Markin, Rodney S.6; Rubin, Raphael7; Wheeler, Donald8; Contos, Melissa5; West, A. B.9; Saldana, Sandra10; Getachew, Yonas11; Butsch, Robert3; Luketic, Velimir12; Peters, Marion13; Di Bisceglie, Adrian14; Bass, Nathan14; Lake, John15; Boyer, Thomas16; Martinez, Enrique17; Boyer, James18; Garcia-Tsao, Guadalupe19; Barnes, David20; Rosenberg, William M.21

1_University of Texas Southwestern Medical Center, Dallas, TX_

2_Applied Epidemiology Group and Liver Group, University of Southampton, Southampton, UK_

3_Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX_

4_University of Texas Southwestern Medical Center at Dallas, Dallas, TX_

5_Department of Pathology, Virginia Commonwealth University Medical Center, Richmond, VA_

6_Department of Pathology and Microbiology, University of Nebraska Medical Center, Lincoln, NE_

7_Departments of Pathology and Anatomy, Thomas Jefferson University, Philadelphia, PA_

8_Departments of Pathology and Cell Biology, University of South Florida, Tampa, FL_

9_Department of Pathology, Yale University, New Haven, CT_

10_Department of Surgery, Loma Linda University, Loma Linda, CA, and the Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas_

11_Department of Medicine, University of Texas Southwestern Medical Center_

12_Virginia Commonwealth University, Richmond, VA_

13_University of California, San Francisco, School of Medicine, San Francisco, CA_

14_Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, MO_

15_Department of Medicine, University of Minnesota, Minneapolis, MN_

16_Arizona Health Sciences Center, Liver Research Institute, Tucson, AZ_

17_Atlanta Gastroenterology Associates, The Liver Center, Atlanta, GA_

18_Department of Internal Medicine, Yale University, New Haven, CT_

19_Yale University School of Medicine and Veterans Administration CT Healthcare System, Department of Internal Medicine, Section of Digestive Diseases_

20_Department of Gastroenterology/A31, The Cleveland Clinic Foundation, Cleveland, OH_

21_Department of Hepatology, University of Southampton, Southampton, UK_

22_Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas_

* Address reprint requests to: UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Room J.5.130A, Dallas, TX 75390-9151

Email:[email protected]

Received 26 February 2008; Accepted 26 June 2008

Published online in Wiley InterScience (www.interscience.wiley.com).

Supported by National Institutes of Health (NIH); Grant Numbers: R21 DK70995 NIH DK46602 NIH M01-RR00633; Grant sponsor: DTI UK-Texas Initiative.

Potential conflict of interest: Nothing to report.

fax: 214-648-0274

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.)

Abbreviations: AUROC, area under the receiver operating characteristic curve; CI, confidence interval; ELF, enhanced liver fibrosis; MELD, Model for End-Stage Liver Disease; PBC, primary biliary cirrhosis; ROC, receiver operating characteristic.