Ombitasvir/ Paritaprevir/ Ritonavir + Ribavirin Combination Therapy in Hepatitis C Virus Infected Patients with Genotype 4 in Real-life Practice: A Multicentre Experience

Abstract

Objective: Objective: Ombitasvir/paritaprevir/ritonavir (OMV/PTV/r) + ribavirin (RBV) combination improved the efficacy, safety, and tolerability of the treatment of chronic hepatitis C virus (HCV) genotype 4 infection. We described the effectiveness and safety of OMV/PTV/r + RBV therapy in patients with genotype 4 infection. Materials and Methods: In this prospective cohort study, HCV genotype 4-infected patients treated with OMV/PTV/r + RBV (n=55) who were registered in a national database were included. Study patients were treatment-naïve or interferon plus RBV-experienced with or without compensated cirrhosis. Demographic, clinical and virological data were analyzed. Details of clinical and laboratory adverse events (AEs) were recorded. Results: The mean age of the patients was 55.2, and 52.7% were male. The majority of patients were non-cirrhotic (81.8%), and 69.1% were treatment-naïve. The HCV RNA level was below 800.000 IU/mL in 16 of the cases. Seventy-eight percent of the patients had an underlying disease. SVR12 rate was 98% in all patients. One patient had virological failure. HCV RNA was undetectable at treatment week 4 in 77.6%, at treatment week 8 in 100%, and at end of treatment in 98%. The SVR12 rates were 100% and 88.9% for those without or with compensated cirrhosis (p= 0.176). Rates of AEs and AEsassociated treatment discontinuation were 69.1% and 3.6% in the patients, respectively. Conclusion: The OBV/PTV/r + RBV combination was found to have high efficacy and safety profile in the patients with chronic HCV genotype 4 infection. This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License. 98 Treatment of Chronic HCV Genotype 4 Infection Aygen et al. INTRODUCTION A bout 170-200 million people are known to be infected with the hepatitis C virus (HCV) worldwide. Chronic hepatitis C (CHC) infection carries risks of hepatic fibrosis, cirrhosis, portal hypertension, liver failure, and hepatocellular carcinoma (HCC) (1-4). Chronic HCV infection is an important health problem in Turkey (5-10). In Turkey, among HCV infections, genotype 1b was reported to be the most common one (90%), while types 2, 3, and 4 exist, with lower prevalence. However, recently, there has been an increase in HCV genotype 4 infections in Turkey (9-13). Two studies from Kayseri reported an unusually high proportion of genotype 4 infections reaching up to 35% among the patients, who were admitted to the hospitals for treatment of CHC (14, 15). This high proportion was significantly higher than the average prevalence of 1.4% reported for type 4 HCV infections in Turkey (15). It was shown recently that Kayseri genotype 4 isolates were closely related to subtype 4d sequences (13, 16). There are several different treatment approaches for HCV genotype 4 infection. By the combination therapy of pegylated interferon (PegINF) and ribavirin (RBV), the sustained virological response (SVR) rate was 60% in patients infected with HCV genotype 4 (17). First-generation protease inhibitors in combination with PegINF and RBV achieved low rates of response in the patients infected with HCV genotype 4, and these regimens were characterised by less favourable safety profiles, which affect adherence to the PegINF-based therapy (7, 11, 12). The novel INF-free second-generation direct-acting antivirals (DAAs) therapy consisting of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) ± RBV improved the efficacy, safety, and tolerability of the treatment of chronic HCV infection. This combination has also proved effective not only in genotype 1 but also in genotype 4. Patients with genotype 4 infection were recommended to be treated with the combination of OBV/PTV/r + RBV, which also resulted in high SVR rates in clinical and real-world trials (18-22). Three of these medications target HCV at different phases of the viral life cycle. Two of them were protease inhibitors: OBV inhibits viral NS5A phosphoprotein, which was involved in virus assembly and PTV inhibited viral NS3-4A serine protease involved in proteolytic processing. Furthermore, ritonavir enhances the pharmacokinetic properties of PTV, increasing their availability through improved drug exposure (23). We aimed to assess the efficacy and safety of OMV/ PTV/r + RBV combination in genotype 4 infected patients in real clinical practice. MATERIALS AND METHODS Study population The patients older than 18 years, with chronic HCV genotype 4 infection, treatment-naïve or previously treated with PegINF/RBV, and chronic hepatitis or compensated cirrhosis were included in the study. The patients with genotype non-4 HCV infection, decompensated liver cirrhosis with Child-Pugh class B or C, evidence of HCC, a concomitant medication that was contraindicated according to manufacturer’s recommendations, current pregnancy, lactation, and platelets count <25.000/mm3 were excluded. We enrolled patients for treatment with OBV/PTV/r + RBV according to the therapeutic guidelines of the National Health Application Notice of the Ministry of Health (24). The clinical information about baseline demographic characteristics, prior treatment status, baseline viral load, liver function tests [bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin], haemoglobin, platelets count, international normalized ratio • There is an increase in HCV genotype 4 infection in Turkey. The regimen of OBV/PTV/r + DSV ± RBV was highly efficacious to treat HCV genotype 4 infection, including patients with compensated cirrhosis. • The patients with chronic HCV genotype 4 infection who were treated with OBV/PTV/r + RBV for 12 weeks achieved 98% SVR12 in our study. Adverse events were mostly mild and did not require medical intervention This cohort is the first to present real-life data in our country. HIGHLIGHTS