Tania M Welzel1, K Rajender Reddy2, Steven L Flamm3, Jill Denning4, Ming Lin4, Rob Hyland4, Phillip S Pang4, John G McHutchison4, Michael Charlton5, Gregory T Everson6, Stefan Zeuzem1, Nezam Afdhal7. 1. Department of Medicine, Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany. 2. Viral Hepatitis Center, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. 3. Division of Gastroenterology and Hepatology, Northwestern Feinberg School of Medicine, Chicago, IL, USA. 4. Gilead Sciences, Inc., Foster City, CA, USA. 5. Division of Hepatology and Liver Transplantation, Intermountain Medical Center, Murray, UT, USA. 6. Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO, USA. 7. Department of Hepatology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Abstract
BACKGROUND: In the Phase II SOLAR-1 study, 12 or 24 weeks of ledipasvir/sofosbuvir and ribavirin yielded high sustained virological response rates at 12 weeks (SVR12) in patients with chronic HCV infection and advanced liver disease, including untransplanted patients with decompensated cirrhosis and liver transplant recipients with all stages of liver disease. METHODS: We performed a post hoc analysis using data from this study to investigate associations between baseline characteristics and early on-treatment HCV RNA, and to determine the utility of early virological response (week 2 and 4) to predict SVR12. Serum HCV RNA was quantified using the Roche COBAS® Ampliprep®/Cobas TaqMan HCV Test, Version 2.0 with a lower limit of quantification (LLOQ) of 15 IU/ml. RESULTS: Most patients achieved HCV RNA <LLOQ by treatment week 4 and target not detected (TND) by week 6. Baseline factors significantly associated with HCV RNA <LLOQ at week 2 were low HCV RNA (<800,000 IU/ml), absence of cirrhosis, age <60 years and no prior treatment experience. At week 4, low HCV RNA, absence of cirrhosis and IL28B CC were associated with <LLOQ, TND. No baseline factors were associated with week 6 response. There was no association between early on-treatment HCV RNA and SVR12. CONCLUSIONS: On-treatment HCV RNA quantification is of limited clinical use in patients with advanced liver disease and/or liver transplantation and does not predict SVR12. ClinicalTrials.gov: NCT01938430.
RCT Entities:
BACKGROUND: In the Phase II SOLAR-1 study, 12 or 24 weeks of ledipasvir/sofosbuvir and ribavirin yielded high sustained virological response rates at 12 weeks (SVR12) in patients with chronic HCV infection and advanced liver disease, including untransplanted patients with decompensated cirrhosis and liver transplant recipients with all stages of liver disease. METHODS: We performed a post hoc analysis using data from this study to investigate associations between baseline characteristics and early on-treatment HCV RNA, and to determine the utility of early virological response (week 2 and 4) to predict SVR12. Serum HCV RNA was quantified using the Roche COBAS® Ampliprep®/Cobas TaqMan HCV Test, Version 2.0 with a lower limit of quantification (LLOQ) of 15 IU/ml. RESULTS: Most patients achieved HCV RNA <LLOQ by treatment week 4 and target not detected (TND) by week 6. Baseline factors significantly associated with HCV RNA <LLOQ at week 2 were low HCV RNA (<800,000 IU/ml), absence of cirrhosis, age <60 years and no prior treatment experience. At week 4, low HCV RNA, absence of cirrhosis and IL28B CC were associated with <LLOQ, TND. No baseline factors were associated with week 6 response. There was no association between early on-treatment HCV RNA and SVR12. CONCLUSIONS: On-treatment HCV RNA quantification is of limited clinical use in patients with advanced liver disease and/or liver transplantation and does not predict SVR12. ClinicalTrials.gov: NCT01938430.