Predicting Clinical and Histologic Outcomes Based on Standard Laboratory Tests in Advanced Chronic Hepatitis C
Background & Aims
Predictors of clinical outcomes and histologic progression among patients with chronic hepatitis C and advanced fibrosis are poorly defined. We developed statistical models to predict clinical and histologic outcomes in such patients.
Methods
Baseline demographic, clinical, and histologic data from Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial participants were subjected to multivariate analyses to determine their ability to predict clinical outcomes (ascites, spontaneous bacterial peritonitis, Child-Turcotte-Pugh score ≥7 on 2 consecutive visits, variceal bleeding, hepatic encephalopathy, and liver-related death) and histologic outcome (≥2-point increase in Ishak fibrosis stage) during the 3.5 years of the trial.
Results
Of 1050 randomized patients, 135 had 1 or more clinical outcomes a median of 23 (range, 1–45) months after randomization. Factors associated with a clinical outcome in multivariate analyses were higher aspartate aminotransferase/alanine aminotransferase ratio, lower albumin, lower platelet count, higher total bilirubin, and more advanced Ishak fibrosis score (P < .0001). The cumulative 3.5-year incidence of a clinical outcome was 2% in the lowest and 65% in the highest risk group. Of 547 patients without cirrhosis at baseline and at least 1 follow-up biopsy, 152 had a histologic outcome. Independent variables associated with a histologic outcome were higher body mass index, lower platelet count, and greater hepatic steatosis (P < .0001).
Conclusions
In patients with chronic hepatitis C and advanced fibrosis, risk of clinical complications and fibrosis progression during 3.5 years can be predicted using baseline laboratory tests and histologic data. Our models may be useful in counseling patients and determining the frequency of monitoring.
Abbreviations used in this paper: AFP, alfa fetoprotein, BMI, body mass index, CTP, Child-Turcotte-Pugh, HAI, histologic activity index, HALT-C, Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis, HCC, hepatocellular carcinoma, HCV, hepatitis C virus, INR, international normalized ratio, MELD, Model for End-Stage Liver Disease, WBC, white blood cell
To access this article, please choose from the options below
Conflicts of interest The authors disclose the following: financial relationships of the authors with Hoffmann-La Roche, Inc, are as follows: A. S. F. Lok is a consultant; G. T. Everson is a consultant, on the speaker's bureau, and receives research support; W. M. Lee receives research support; R. K. Sterling is consultant, on the speaker's bureau, and receives research support; A.M. Di Bisceglie is a consultant, on the speaker's bureau, and receives research support; H. L. Bonkovsky receives research support; and T. R. Morgan is a consultant, on the speaker's bureau, and receives research support. The remaining authors disclose no conflicts.
In addition, many of the HALT-C Trial investigators have other associations with industry relating to the area of hepatitis C, and, to achieve the highest level of disclosure, we list these for you as well.
A. S. F. Lok: Schering-Plough Corporation, consultant and receives research support; Vertex Pharmaceuticals, consultant; Idenix Pharmaceuticals, receives research support; Eisai Pharmaceuticals, receives research support. G. T. Everson: receives research support from Schering-Plough, Pharmasset, GlobeImmune, Source, Novartis/Human Genome Sciences, and GlaxoSmithKline and is a consultant and receives research support from Vertex Pharmaceuticals. W. M. Lee: receives research support from Aegerion, GlobeImmune, Orasure, Schering-Plough, Siemens Diagnostics, and Vertex Pharmaceuticals. A.M. Stoddard: equity interest in Johnson & Johnson, Procter & Gamble, Bristol-Myers Squibb, and Elan. R. K. Sterling: consultant and on the speaker's bureau for Schering-Plough; is on an advisory board for Vertex Pharmaceuticals; and is a consultant and receives research support from Wako Chemicals USA. A. M. Di Bisceglie: consultant, on the speaker's bureau, and receives research support from Idenix Pharmaceuticals; is a consultant for Schering-Plough, Novartis, Bristol-Myers Squibb, and Abbott; is a consultant and receives research support from Vertex Pharmaceuticals, Anadys, GlobeImmune, Pharmasset, Sci-Clone, Gilead Sciences, and Novartis. H. L. Bonkovsky: serves on a data monitoring and safety committee for Glaxo Smith Kline; served as a paid consultant for Boehringer-Ingelheim and Infacare Pharmaceuticals receives research support from Merck; consultant and receives research support from Novartis Pharmaceuticals; consultant and on speaker's bureau for Ovation, Inc; receives research support from Schering-Plough Corporation; receives research support from Vertex Pharmaceuticals. T. R. Morgan: is on the speaker's bureau and receives research support from Schering-Plough and is a consultant and receives research support from Vertex Pharmaceuticals. J. L. Dienstag: receives research support from Vertex Pharmaceuticals; serves on a Data Monitoring Committee for Schering-Plough Research Institute and Human Genome Sciences; and is on ad hoc hepatitis advisory board for Boehringer-Ingelheim.
Funding Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below) and the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.
PII: S0016-5085(09)01599-6
doi:10.1053/j.gastro.2009.09.007
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
