The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Ombitasvir/paritaprevir/ritonavir & Dasabuvir ± Ribavirin Following Protease Inhibitors Failure - A Prospective Multi-Centre Trial
Liat Deutsch12, Inbal Houri12, Ziv Ben-Ari23, Amir Shlomai24, Ella Veitsman23, Oranit Cohen-Ezra23, Assaf Issachar24, Orna Mor56, Yael Gozlan5, Rafael Bruck12, Yoram Menachem12, Shira Zelber-Sagi17, Helena Katchman12, Oren Shibolet89
Author information
1Department of Gastroenterology and Liver diseases, Tel Aviv Sourasky Medical Centre and Tel-Aviv University, 6 Weizmann St, 64239, Tel-Aviv, Israel.
2Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
3The liver Centre, Sheba Medical Centre, Ramat Gan, Israel.
4The Liver Institute, Rabin Medical Centre, Beilinson Hospital, Petah-Tikva, Israel.
5Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Centre, Ramat-Gan, Israel.
6Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
7School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.
8Department of Gastroenterology and Liver diseases, Tel Aviv Sourasky Medical Centre and Tel-Aviv University, 6 Weizmann St, 64239, Tel-Aviv, Israel. orensh@tlvmc.gov.il.
9Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel. orensh@tlvmc.gov.il.
Abstract
Background: Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma. Treatment with first generation protease inhibitors (PI) + peg-interferon (pegIFN) and ribavirin (RBV) achieved sustained virologic response (SVR) rates of 65-75% but was associated with multiple side effects. The aim of this study was to evaluate safety and efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir (3D) ± RBV in HCV genotype 1 patients that failed previous treatment with first generation PIs.
Methods: An investigator-initiated, open-label, multi-centre clinical trial. HCV Genotype 1 patients who were previously null/partial responders or relapsers to telaprevir, boceprevir or simepravir+pegIFN/RBV and met eligibility criteria were included. 3D ± RBV were administrated for 12 or 24 weeks according to label. The primary outcome was antiviral response (SVR12); Secondary outcomes were patient reported outcomes, adverse events and resistance associated variants.
Results: Thirty-nine patients initiated treatment according to study protocol (59% men, age 54.0 ± 8.7 years, BMI 28.7 ± 4.5 kg/m2). Thirty-seven (94.9%) completed the study. Thirty-five patients had genotype 1b (9 cirrhotics) and 4 had genotype 1a (2 cirrhotics). Intention-to-treat SVR12 was 92.3% and per-protocol SVR12 was 97.3%. The rate of advanced fibrosis (FibroScan® score F3-4) declined from 46.2 to 25.7% (P = 0.045). Abnormal ALT levels declined from 84.6 to 8.6% (P < 0.001). Seven patients (17.9%) experienced serious adverse events (3 Psychiatric admissions, 1 pneumonia, 1 ankle fracture, 2 palpitations), and 12 patients (30.8%) experienced self-reported adverse events, mostly weakness.
Conclusion: 3D ± RBV is safe and effective in achieving SVR among patients with HCV genotype 1 who failed previous first-generation PI treatment.
Trial registration: NCT02646111 (submitted to ClinicalTrials.gov, December 28, 2015).