Ombitasvir/paritaprevir/ritonavir & dasabuvir ± ribavirin following protease inhibitors failure - a prospective multi-centre trial

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/m 2). 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.

Hepatitis C related cognitive impairment: Impact of viral and host factors and response to therapy

“…As described elsewhere, 12 OPRD effectively achieved viral eradication in all 32 subjects enrolled in our study. Viral eradication resulted in improved post‐treatment liver enzymes tests, albumin and LS values.…”

“…This study was a part of the EMERALD study, an open‐label single‐arm multicentre study of AbbVie 3D regimen for the treatment of HCV 1st generation protease inhibitor failure described, elsewhere 12 . Briefly, the efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir (OPRD) ± ribavirin were determined in patients with HCV genotype 1 who previously failed treatment with first‐generation protease inhibitors +pegylated interferon (IFN) and ribavirin.…”

Analysis of the global situation of COVID-19 research based on bibliometrics

“…In addition to developing diagnostic reagents, researchers have developed a deep learning-based chest CT model for the automatic detection of COVID-19 (Zheng et al unpublished). In terms of the clinical treatment, researchers have not yet identified a specific treatment for COVID-19, but the disease has been treated with antiviral drugs, such as -interferon [ 7 ], lopinavir [ 6 ], ritonavir [ 6 ], ribavirin [ 2 ], chloroquine phosphate [ 10 ], and remdesivir [ 6 ].…”

Effectiveness of retreatment with ombitasvir/paritaprevir/ritonavir and dasabuvir+sofosbuvir+ribavirin in patients with chronic hepatitis C, subtype 1b, and cirrhosis, who failed previous treatment with first‐ and second‐generation NS5A inhibitors

“…Several studies were dedicated to the question of 3D±RBV effectiveness in patients infected with HCV GT 1b who had earlier failed treatment with first‐ or second‐generation NS3 inhibitors (telaprevir + PEG + RBV or boceprevir + PEG + RBV or SIM + PEG + RBV), including 87.4% subjects with liver cirrhosis. Retreatment during 12 and 24 weeks in such patients resulted in the high likelihood of achieving SVR 96.2%–99.0% 25–27 …”