S1001
Clearance of HCV At 5 Year Follow-Up for Peginterferon Alfa-2b ± Ribavirin Is Predicted By Sustained Virologic Response At 24 Weeks Post Treatment
Karen Lindsay¹, Michael P Manns², Stuart C Gordon³, Paul Pockros⁴, Dieter Haussinger⁵, Stephanos J Hadziyannis⁶, Warren N Schmidt⁷, Ira M Jacobson⁸, Rafael Barcena⁹, Eugene Schiff¹⁰, Obaid S Shaikh¹¹, Bruce R Bacon¹², Patrick Marcellin¹³, Coleman I Smith¹⁴, John G McHutchison¹⁵, Weipeng Deng¹⁶, Lisa D Pedicone¹⁶, Janice Albrecht¹⁶
1. USC Keck School of Medicine, Los Angeles, CA, USA, 2. Medical School of Hannover, Hannover, Germany, 3. Henry Ford Hospital, Detroit, MI, USA, 4. Scripps Clinic, La Jolla, CA, USA, 5. Universitaetsklinikum, Duesseldorf, Germany, 6. Evgenidion Hospital, Athens, Greece, 7. University of Iowa, Iowa City, IA, USA, 8. Weill Medical College of Cornell University, New York, NY, USA, 9. Hospital Ramon y Cajal, Madrid, Spain, 10. University of Miami, Miami, FL, USA, 11. University of Pittsburgh, Pittsburgh, PA, USA, 12. St. Louis University, St. Louis, MO, USA, 13. Hopital Beaujon, Clichy, France, 14. Minnesota Clinical Research Center, Plymouth, MN, USA, 15. Duke University, Durham, NC, USA, 16. Schering Plough Research Institute, Kenilworth, NJ, USA

Background and Aims: Sustained virologic response (SVR) 24 weeks after treatment of chronic hepatitis C virus (HCV) infection with interferon alfa-2b (IFN) ± ribavirin (RBV) predicts long-term clearance (>5 years) of HCV from serum in adults (McHutchison, et al, J Hepatol 2006;44[suppl 2]:S275). The aim of the current study was to confirm this finding in patients treated with peginterferon alfa-2b ± ribavirin (PEG±riba). Methods: 567/1695 (33%) subjects from 2 clinical trials (Lindsay et al, Hepatology 2001;34:395-403; Manns et al, Lancet 2001;358:958-965) who were treated with PEG±riba and completed 24 weeks of follow-up were assessed annually for up to 5 years for clinical evidence of liver disease progression and virologic evidence of relapse. Results: 366 sustained responders (SRs) and 201 who were not sustained responders (NSRs) entered the study and were followed for a mean of 248 and 232 weeks, respectively. 85% and 62% of SRs and 77% and 50% of NSRs completed 3 and 5 years of follow-up, respectively. Four SR subjects relapsed during the 5-year follow-up period (2 at year 1, 1 at year 2, and 1 at year 5). Kaplan-Meier estimate for continued sustained response over 5 years was 99% (95% CI: 97%-100%). Of the 192 SRs with normal ALT values at the end of the initial 24 week follow-up, 174 (91%) remained normal throughout the 5-year follow-up period. Most abnormal ALT values were slightly above the upper limit of normal (ULN), and the highest elevation remained <5×ULN. Progression of liver disease occurred in 1 subject in the NSR group (bleeding varices) and no subjects in the SR group. Five SR subjects died during follow-up, and all deaths were unrelated to liver disease progression or PEG±riba administration (prostate cancer, adenocarcinoma of lung, myocardial infarction, coronary embolism, ventricular fibrillation). Serious adverse events were reported for 64 subjects: 3 had events that were considered possibly related to PEG±riba (papillary thyroid cancer; peripheral neuropathy + hypertension; ureteral calculi). Conclusions: For patients responding to PEG±riba therapy, SVR at 24 weeks post treatment predicts long-term clearance of HCV. These results confirm those of McHutchison and suggest that successful treatment (SVR) of HCV with interferon (±riba) leads to a clinical cure of this chronic disease.