Liver Failure/Cirrhosis/Portal Hypertension
Article first published online: 14 SEP 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 51, Issue 2, pages 585–594, February 2010
How to Cite
Everhart, J. E., Wright, E. C., Goodman, Z. D., Dienstag, J. L., Hoefs, J. C., Kleiner, D. E., Ghany, M. G., Mills, A. S., Nash, S. R., Govindarajan, S., Rogers, T. E., Greenson, J. K., Brunt, E. M., Bonkovsky, H. L., Morishima, C., Litman, H. J. and HALT-C Trial Group (2010), Prognostic value of Ishak fibrosis stage: Findings from the hepatitis C antiviral long-term treatment against cirrhosis trial. Hepatology, 51: 585–594. doi: 10.1002/hep.23315
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.
The HALT-C Trial was registered with clinicaltrials.gov (#NCT00006164).
Potential conflict of interest: Dr. Hoefs is on the speakers' bureau of Roche and Gilead. Dr. Greenson is a consultant for Roche, Millennium, and GlaxoSmithKline. Dr. Bonkovsky is a consultant for and advises Boehringer-Ingelheim and Novartis. He also advises and is on the speakers' bureau of Lundbeck Pharma. He received grants from Hoffmann-LaRoche, Merck, and Vortex.
- Issue published online: 25 JAN 2010
- Article first published online: 14 SEP 2009
- Accepted manuscript online: 14 SEP 2009 12:00AM EST
- Manuscript Accepted: 3 SEP 2009
- Manuscript Received: 24 JUL 2009
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Cancer Institute
- National Center for Minority Health and Health Disparities
- General Clinical Research Center
- Clinical and Translational Science Center grants from the National Center for Research Resources
- National Institutes of Health
- Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health
Studies of the prognostic value of Ishak fibrosis stage are lacking. We used multi-year follow-up of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial to determine whether individual Ishak fibrosis stages predicted clinical outcomes in patients with chronic hepatitis C. Baseline liver biopsy specimens from 1050 patients with compensated chronic hepatitis C who had failed combination peginterferon and ribavirin were reviewed by a panel of expert hepatopathologists. Fibrosis was staged with the Ishak scale (ranging from 0 = no fibrosis to 6 = cirrhosis). Biopsy fragmentation and length as well as number of portal tracts were recorded. We compared rates of prespecified clinical outcomes of hepatic decompensation and hepatocellular carcinoma across individual Ishak fibrosis stages. Of 1050 biopsy specimens, 25% were fragmented, 63% longer than 1.5 cm, 69% larger than 10 mm2, and 75% had 10 or more portal tracts. Baseline laboratory markers of liver disease severity were worse and the frequency of esophageal varices higher with increasing Ishak stage (P < 0.0001). The 6-year cumulative incidence of first clinical outcome was 5.6% for stage 2, 16.1% for stage 3, 19.3% for stage 4, 37.8% for stage 5, and 49.3% for stage 6. Among nonfragmented biopsy specimens, the predictive ability of Ishak staging was enhanced; however, no association was observed between Ishak stage and outcomes for fragmented biopsy specimens because of high rates of outcomes for patients with noncirrhotic stages. Similar results were observed with liver transplantation or liver-related death as the outcome. Conclusion: Ishak fibrosis stage predicts clinical outcomes, need for liver transplantation, and liver-related death in patients with chronic hepatitis C. Patients with fragmented biopsy specimens with low Ishak stage may be understaged histologically. (HEPATOLOGY 2010;51:585–594.)