Real-world experience of efficacy and safety using paritaprevir/ritonavir, ombitasvir and dasabuvir for advanced fibrotic genotype 1 chronic hepatitis c patients who failed to previous therapy with pegylated interferon plus ribavirin

Background: Treatment of chronic hepatitis C (CHC) evolved rapidly in recent years due to the invention of interferon-free direct antiviral agents. Based on the data obtained from clinical trials, combination therapy with paritaprevir/ritonavir, ombitasvir and dasabuvir (PrOD) with or without ribavirin (RBV) have been showed to cure over 95% CHC patients infected by genotype 1 hepatitis C virus (HCV), regardless cirrhosis or not. However, real-world data regarding the efficacy and safety of PrOD-based therapy in Asian HCV genotype 1 CHC patients are limited, especially for advanced fibrotic patients who failed previous therapy with pegylated interferon (Peg-IFN) plus RBV. Therefore we conducted this study to address these important issues. Method(s): Between January and April 2017, a total of 47 advanced fibrotic ([=F3) genotype 1 CHC patients who failed to previous therapy with Peg-IFN and received PrOD-based therapy for 12 weeks at Taipei Veterans General Hospital were retrospectively enrolled. Weight-based RBV 800-1200 mg/day was added for all HCV geno-type 1a and 1b patients with cirrhosis. Advanced fibrosis was defined by liver stiffness measurement by transient elastography (FibroScan)? 9.5 kPa. Patients were excluded for analyses if they had history of hepatic decompensation, mixed infection with HCV other than genotype 1 and coinfection with hepatitis B virus. Serum quantitative HCV RNA level was determined by real-time PCR (Cobas Taqman HCV Test v2.0, Roche Diagnostics) with lower detection limit of 15 IU/mL. Sustained virological response (SVR) was defined by undetectable HCV RNA at the end and 12 weeks after the completion of therapy. Result(s): The mean age of enrolled population was 63.5+/-9.7 years, 20 (42.6%) of them was male and 15 (31.9%) diagnosed to have liver cirrhosis. The mean baseline HCV RNA level was 6.28+/-0.84 log10 IU/mL and 93.6% (44/47) were infected by HCV genotype 1b. Pre-vious treatment history of Peg-IFN was as follows: relapser 68.1%, partial or null responder 27.6% and early terminated due to intolerance of side effects: 4.3%. After PrOD-based therapy, the rates undetectable HCV at week 2, 4 and 12 were 59.6%, 89.4% and 100%, respectively. 57.8% (11/19) patients with detectable HCV RNA at week 2 were\100 IU/mL. Fatigue, pruritus, skin rash, insomnia and headache were most common patient reported adverse effects. Grade 2 (1.5*3.0 X ULN) hyperbilirubinemia were found in 12.8% (6/47) patients during study period and all of them belonged to unconjugated hyperbilirubinemia. No patients had grade 3 or 4 hyperbilirubinemia during study period and all patients finished 12 weeks PrOD-based therapy. After post-treatment follow up, all 47 patients (100%) achieved SVR. Conclusion(s): Our real world data in Taiwan demonstrated PrOD-based therapy with or without RBV is well-tolerated and highly effective for genotype 1 CHC patients with advanced fibrosis who failed to previous therapy with Peg-IFN plus RBV.