Outcome of Sustained Virological Responders With... : Hepatology (original) (raw)

Viral Hepatitis

Outcome of Sustained Virological Responders With Histologically Advanced Chronic Hepatitis C†,‡,§,¶

Morgan, Timothy R.*,1,2,#; Ghany, Marc G.3; Kim, Hae-Young4; Snow, Kristin K.4; Shiffman, Mitchell L.5; De Santo, Jennifer L.6; Lee, William M.7; Di Bisceglie, Adrian M.8; Bonkovsky, Herbert L.9, 14; Dienstag, Jules L.10; Morishima, Chihiro11; Lindsay, Karen L.12; Lok, Anna S. F.13 and the HALT-C Trial Group

1 Division of Gastroenterology, University of California Irvine, Irvine, CA

2 Gastroenterology Service, Veterans Affairs Long Beach Healthcare System, Long Beach, CA

3 Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD

4 New England Research Institutes, Watertown, MA

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

6 Division of Gastroenterology and Hepatology, University of Colorado at Denver and Health Sciences Center, Denver, CO

7 Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX

8 Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO

9 Departments of Medicine and Molecular and Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT

10 Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, and the Department of Medicine, Harvard Medical School, Boston, MA

11 Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA

12 Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA

13 Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI

14 Carolinas Medical Center, Charlotte, NC

*Address reprint requests to: Timothy R. Morgan, M.D, VA Long Beach Healthcare System–11 (GI), 5901 East Seventh Street, Long Beach, CA 90822.

E-mail:[email protected]

Received March 05, 2010; accepted April 26, 2010; previously published online May 14, 2010

†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

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Abstract

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.