Abstract
BackgroundHepatitis 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.MethodsAn 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.ResultsThirty-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.Conclusion3D ± RBV is safe and effective in achieving SVR among patients with HCV genotype 1 who failed previous first-generation PI treatment.Trial registrationNCT02646111 (submitted to ClinicalTrials.gov, December 28, 2015).
Highlights
Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and hepatocellular carcinoma
Post-treatment analysis was performed only to patient no. 28, which was similar to the pre-treatment pattern and showed resistance to all NS3 protease inhibitors and to all NS5A inhibitors except pibrentasvir. In this open-label, prospective, multi-centre clinical trial, treatment of HCV infected patients that failed previous PI treatment with a combination of ombitasvir/paritaprevir/ ritonavir and dasabuvir for 12/24 weeks ± RBV, resulted in SVR12 rates of 92% of all patients, and 97% of those who completed the treatment, similar to those reported with other second-generation treatment regimens
This study demonstrates the efficacy of 3D pegIFN-free regimen for the treatment of chronic HCV genotype 1 (GT1) infection after previous virologic failure on first generation PIs
Summary
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. Hepatitis C viral (HCV) infection is a leading cause of liver cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation [1]. The early-PIs required co-administration of pegylated interferon (pegIFN) and ribavirin (RBV) These triple therapy regimens achieved markedly improved sustained virologic response (SVR) rates of approximately 65–75% [4, 5] as compared to the older pegIFN+RBV regimen. In addition to the various contraindications to pegIFN+RBV and their known side effects, these PIs had numerous and often severe side effects, necessitating discontinuation of therapy in as many as 25% of patients
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