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Effect of Sofosbuvir Plus Daclatasvir in Hepatitis C Virus Genotype-4 Patients: Promising Effect on Liver Fibrosis.

ABSTRACT: Background/purpose:The effect of sofosbuvir and daclatasvir in treatment of genotype 4 Hepatitis C Virus (HCV) is not well documented. This study investigated the safety and efficacy of sofosbuvir plus daclatasvir with or without ribavirin in treatment of HCV genotype 4 patients. The impact of therapy on liver fibrosis as well as the role of IL18 polymorphism in therapeutic outcome was assessed. Methods:One hundred HCV genotype 4 patients were categorized into 2 groups. The group 1 comprised treatment naïve patients, with total serum bilirubin ? 1.2 mg/10-1 L, serum albumin ? 3.5 g/10-1 L, INR ? 1.2, and platelet count ? 150 × 109/L. This group was treated with sofosbuvir plus daclatasvir for 12 weeks. The group 2 included Peg-IFN-?-or sofosbuvir treatment experienced, or patients with at least 2 of the following findings: total serum bilirubin > 1.2 mg/10-1 L, serum albumin < 3.5 g/10-1 L, INR > 1.2, and platelet count < 150 × 109 L-1. Group 2 was treated with sofosbuvir-daclatasvir + ribavirin for 12 weeks, with the exception of sofosbuvir treatment experienced patients, who were treated with sofosbuvir/daclatasvir + ribavirin for 24 weeks. Results:Sustained Virological Response (SVR12) (undetectable viremia12 weeks post-treatment), was 93.3% in group 1 and 87.5% in group 2 (total = 91%). Such high efficacy was accompanied with tolerable adverse effects as well as with significant improvement in liver fibrosis. No significant association was observed between IL18 polymorphism (rs1946518) at position -607 and achievement of SVR12 in HCV patients after treatment. Conclusion:Sofosbuvir plus daclatasvir, with or without ribavirin achieved high efficacy and safety in HCV genotype 4 patients. Their effects were accompanied with attenuation of liver fibrosis. Further wider-scale studies are needed to evaluate the actual role of IL18 polymorphisms in treatment response with sofosbuvir/daclatasvir.

SUBMITTER: Abdel-Aziz AM

PROVIDER: S-EPMC5938328 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Effect of Sofosbuvir Plus Daclatasvir in Hepatitis C Virus Genotype-4 Patients: Promising Effect on Liver Fibrosis.

Abdel-Aziz Asmaa M AM Ibrahim Mohamed A MA El-Sheikh Azza A AA Kamel Maha Y MY Zenhom Nagwa M NM Abdel-Raheim Salam S Abdelhaleem Hisham H

Journal of clinical and experimental hepatology 20170630 1

<h4>Background/purpose</h4>The effect of sofosbuvir and daclatasvir in treatment of genotype 4 Hepatitis C Virus (HCV) is not well documented. This study investigated the safety and efficacy of sofosbuvir plus daclatasvir with or without ribavirin in treatment of HCV genotype 4 patients. The impact of therapy on liver fibrosis as well as the role of IL18 polymorphism in therapeutic outcome was assessed.<h4>Methods</h4>One hundred HCV genotype 4 patients were categorized into 2 groups. The group ...[more]

PMID: 29743792

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Project description:To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection.Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in DUAL-treated patients compared with placebo patients during the first 12 wk (double-blind phase), and during 24 wk of DUAL in both arms combined.In total, 207 patients were randomly assigned to immediate (n = 155) or placebo-deferred (n = 52) treatment. Most patients were Asian (86%), female (59%) and aged < 65 years (90%). Among them, 13% had cirrhosis, 32% had IL28B non-CC genotypes and 53% had baseline HCV RNA levels of ? 6 million IU/mL. Among patients in the immediate treatment arm, SVR12 was achieved by 92% (95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate (70%). SVR12 was largely unaffected by cirrhosis (89%), age ? 65 years (92%), male sex (90%), baseline HCV RNA ? 6 million (89%) or IL28B non-CC genotypes (96%), although SVR12 was higher among patients without (96%) than among those with (53%) baseline NS5A resistance-associated polymorphisms (at L31 or Y93H). During the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving DUAL. During 24 wk of DUAL therapy (combined arms), the most common adverse events (? 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities (alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued DUAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.DUAL was well-tolerated during this phase 3 study, and SVR12 with DUAL treatment (92%) exceeded the historical SVR rate for peg-interferon plus ribavirin of 70%.

Project description:Chronic hepatitis C virus (HCV) infection with advanced cirrhosis or post-liver transplantation recurrence represents a high unmet medical need with no approved therapies effective across all HCV genotypes. The open-label ALLY-1 study assessed the safety and efficacy of a 60-mg once-daily dosage of daclatasvir (pan-genotypic NS5A inhibitor) in combination with sofosbuvir at 400 mg once daily (NS5B inhibitor) and ribavirin at 600 mg/day for 12 weeks with a 24-week follow-up in two cohorts of patients with chronic HCV infection of any genotype and either compensated/decompensated cirrhosis or posttransplantation recurrence. Patients with on-treatment transplantation were eligible to receive 12 additional weeks of treatment immediately after transplantation. The primary efficacy measure was sustained virologic response at posttreatment week 12 (SVR12) in patients with a genotype 1 infection in each cohort. Sixty patients with advanced cirrhosis and 53 with posttransplantation recurrence were enrolled; HCV genotypes 1 (76%), 2, 3, 4, and 6 were represented. Child-Pugh classifications in the advanced cirrhosis cohort were 20% A, 53% B, and 27% C. In patients with cirrhosis, 82% (95% confidence interval [CI], 67.9%-92.0%) with genotype 1 infection achieved SVR12, whereas the corresponding rates in those with genotypes 2, 3, and 4 were 80%, 83%, and 100%, respectively; SVR12 rates were higher in patients with Child-Pugh class A or B, 93%, versus class C, 56%. In transplant recipients, SVR12 was achieved by 95% (95% CI, 83.5%-99.4%) and 91% of patients with genotype 1 and 3 infection, respectively. Three patients received peritransplantation treatment with minimal dose interruption and achieved SVR12. There were no treatment-related serious adverse events.The pan-genotypic combination of daclatasvir, sofosbuvir, and ribavirin was safe and well tolerated. High SVR rates across multiple HCV genotypes were achieved by patients with post-liver transplantation recurrence or advanced cirrhosis.

Dataset Information

Effect of Sofosbuvir Plus Daclatasvir in Hepatitis C Virus Genotype-4 Patients: Promising Effect on Liver Fibrosis.

Publications

Effect of Sofosbuvir Plus Daclatasvir in Hepatitis C Virus Genotype-4 Patients: Promising Effect on Liver Fibrosis.

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