Article first published online: 14 MAY 2010
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 52, Issue 3, pages 833–844, September 2010
How to Cite
Morgan, T. R., Ghany, M. G., Kim, H.-Y., Snow, K. K., Shiffman, M. L., De Santo, J. L., Lee, W. M., Di Bisceglie, A. M., Bonkovsky, H. L., Dienstag, J. L., Morishima, C., Lindsay, K. L., Lok, A. S. F. and and the HALT-C Trial Group (2010), Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology, 52: 833–844. doi: 10.1002/hep.23744
Potential conflict of interest: T.R.M. is on the speaker's bureau and receives research support from Hoffmann-La Roche, Inc.; K.L.L. was a consultant and received research support from Hoffmann-La Roche, Inc. during this study and is now an employee of Tibotec, Inc. (a subsidiary of Johnson & Johnson), Yardley, NJ; A.S.L. is a consultant for Hoffmann-La Roche Inc.; M.L.S. is a consultant for Hoffmann-La Roche, Inc.; W.M.L. receives research support from Hoffmann-La Roche, Inc.; A.M.D. is a consultant and receives research support from Hoffmann-La Roche, Inc.; and H.L.B. receives research support from Hoffmann-La Roche, Inc. Authors with no financial relationships related to this project are: M.G.G., H.-Y.K., K.K.S., J.L.D., J.L.D., and C.M.
This is publication #51 of the HALT-C Trial.
The HALT-C Trial was registered with clinicaltrials.gov (#NCT00006164).
For financial support information, see grant numbers listed in the acknowledgment
- Issue published online: 26 AUG 2010
- Article first published online: 14 MAY 2010
- Manuscript Accepted: 26 APR 2010
- Manuscript Received: 5 MAR 2010
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- National Cancer Institute
- National Center for Minority Health and Health Disparities
- General Clinical Research Center and Clinical and Translational Science Center grants
- National Center for Research Resources
- National Institutes of Health
- Hoffmann-La Roche, Inc.,
- National Institutes of Health.
- University of Massachusetts Medical Center, Worcester, MA. Grant Number: N01-DK-9-2326
- University of Connecticut Health Center, Farmington, CT. Grant Number: M01RR-06192
- Saint Louis University School of Medicine, St Louis, MO. Grant Number: N01-DK-9-2324
- Massachusetts General Hospital, Boston, MA. Grant Numbers: N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01
- Harvard Clinical and Translational Science Center
- University of Colorado Denver, School of Medicine, Aurora, CO. Grant Numbers: N01-DK-9-2327, M01RR-00051, 1 UL1 RR 025780-01
- University of California-Irvine, Irvine, CA. Grant Numbers: N01-DK-9-2320, M01RR-00827
- University of Texas Southwestern Medical Center, Dallas, TX. Grant Numbers: N01-DK-9-2321, M01RR-00633, 1 UL1 RR024982-01
- North and Central Texas Clinical and Translational Science Initiative
- University of Southern California, Los Angeles, CA. Grant Numbers: N01-DK-9-2325, M01RR-00043
- University of Michigan Medical Center, Ann Arbor, MI. Grant Numbers: N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986
- Michigan Center for Clinical and Health Research
- Virginia Commonwealth University Health System, Richmond, VA. Grant Numbers: N01-DK-9-2322, M01RR-00065)
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, M.D.
- National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, M.D.
- University of Washington, Seattle, WA. Grant Number: N01-DK-9-2318
- New England Research Institutes, Watertown, MA. Grant Number: N01-DK-9-2328
- Armed Forces Institute of Pathology, Washington, DC
Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR), and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial. Laboratory and/or clinical outcome data were available for 140 of the 180 patients who achieved SVR. Patients with nonresponse (NR; n = 309) or who experienced breakthrough or relapse (BT/R; n = 77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Median follow-up for the SVR, BT/R, and NR groups of patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that of the NR group (21.3% and 27.2%, P < 0.001 for both) but not the BT/R group (4.4% and 8.7%). The adjusted hazard ratio (HR) for time to death/liver transplantation (HR = 0.17, 95% confidence interval [CI] = 0.06-0.46) or development of liver-related morbidity/mortality (HR = 0.15, 95% CI = 0.06-0.38) or HCC (HR = 0.19, 95% CI = 0.04-0.80) was significant for SVR compared to NR. Laboratory tests related to liver disease severity improved following SVR. Conclusion: Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC. (HEPATOLOGY 2010;)