Quantitative liver function tests improve the prediction of ... : Hepatology (original) (raw)

Viral Hepatitis

Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: Results from the hepatitis C antiviral long-term treatment against cirrhosis trial

Everson, Gregory T.1,*; Shiffman, Mitchell L.2; Hoefs, John C.3; Morgan, Timothy R.3; Sterling, Richard K.4; Wagner, David A.5; Lauriski, Shannon1; Curto, Teresa M.6; Stoddard, Anne6; Wright, Elizabeth C.7 the HALT-C Trial Group

1 Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO

2 Liver Institute of Virginia, Bon Secours Health System, Newport News, VA

3 Division of Gastroenterology, University of California, Irvine, Irvine, CA and Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA

4 Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA

5 Metabolic Solutions, Inc., Nashua, NH

6 New England Research Institutes, Watertown, MA

7 Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD

* Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado Denver, 1635 North Aurora Court, B-154, Aurora, CO 80045

Email: [email protected]

Received 11 August 2011; Accepted 3 October 2011

Grant sponsor: National Institute of Diabetes and Digestive and Kidney Diseases; Grant Numbers: N01-DK-9–2327 M01RR-00051 N01-DK-9–2320 M01RR-00827 N01-DK-9–2322 M01RR-00065 N01-DK-9–2328 National Institute of Allergy and Infectious Diseases National Cancer Institute National Center for Minority Health and Health Disparities; Grant sponsor: General Clinical Research Center; Grant sponsor: National Center for Research Resources; Grant sponsor: National Institutes of Health; Grant sponsor: Metabolic Solutions, Inc.; Grant sponsor: Hoffmann-La Roche, Inc.; Grant sponsor: Cooperative Research and Development Agreements; Grant sponsor: National Institutes of Health.

Potential conflict of interest: G.T. Everson, M. L. Shiffman, T. R. Morgan, and R. K. Sterling are consultants and receive research support and J.C. Hoefs is on the speaker's bureau with Hoffmann LaRoche, Inc. D.A. Wagner is employed, has equity, and has intellectual property rights with Metabolic Solutions. G. T. Everson has intellectual property rights related to the University of Colorado Denver filing of US Patent Application No. 60/647,689, “Methods for Diagnosis and Intervention of Hepatic Disorders”, 26 January 2005, and International Application Number PCT/US2006/003132 as published under the Patent Cooperation Treaty, World Intellectual Property Organization, International Patent Classification A61K 49/00 (2006.01), International Publication Number WO 2006/081521 A2, 3 August 2006 (03.08.2006). G. T. Everson has equity interest in HepQuant LLC. Authors with no financial relationships to disclose are: S. Lauriski, T.M. Curto, A. Stoddard, and E.C. Wright.

This is publication number 70 from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial Group. The HALT-C Trial is registered with clinicaltrials.gov (NCT00006164).

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Abstract

Risk for future clinical outcomes is proportional to the severity of liver disease in patients with chronic hepatitis C virus (HCV). We measured disease severity by quantitative liver function tests (QLFTs) to determine cutoffs for QLFTs that identified patients who were at low and high risk for a clinical outcome. Two hundred and twenty-seven participants in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial underwent baseline QLFTs and were followed for a median of 5.5 years for clinical outcomes. QLFTs were repeated in 196 patients at month 24 and in 165 patients at month 48. Caffeine elimination rate (kelim), antipyrine (AP) clearance (Cl), MEGX concentration, methionine breath test (MBT), galactose elimination capacity (GEC), dual cholate (CA) clearances and shunt, perfused hepatic mass (PHM), and liver and spleen volumes (by single-photon emission computed tomography) were measured. Baseline QLFTs were significantly worse (P = 0.0017 to P < 0.0001) and spleen volumes were larger (P < 0.0001) in the 54 patients who subsequently experienced clinical outcomes. QLFT cutoffs that characterized patients as “low” and “high risk” for clinical outcome yielded hazard ratios ranging from 2.21 (95% confidence interval [CI]: 1.29–3.78) for GEC to 6.52 (95% CI: 3.63–11.71) for CA clearance after oral administration (Cloral). QLFTs independently predicted outcome in models with Ishak fibrosis score, platelet count, and standard laboratory tests. In serial studies, patients with high-risk results for CA Cloral or PHM had a nearly 15-fold increase in risk for clinical outcome. Less than 5% of patients with “low risk” QLFTs experienced a clinical outcome. Conclusion: QLFTs independently predict risk for future clinical outcomes. By improving risk assessment, QLFTs could enhance the noninvasive monitoring, counseling, and management of patients with chronic HCV. (Hepatology 2012)