Safety Of Daclatasvir Research Articles

Effect of Antiviral Drug on Viral Load Patients Infected with Hepatitis C Virus Genotype 3

Background: Hepatitis C Virus (HCV) genotype 3 is recognized for its rapid progression towards liver fibrosis, cirrhosis, and increased risk of hepatocellular carcinoma, particularly in regions with high prevalence rates like Pakistan. Despite advances in treatment, understanding the efficacy and outcomes of direct-acting antiviral (DAA) therapy in this specific genotype remains crucial for optimizing clinical management and public health strategies. Objective: This study aims to evaluate the efficacy and safety of daclatasvir and sofosbuvir combination therapy in patients with HCV genotype 3 infection, focusing on sustained virologic response (SVR), viral load reduction, and treatment-related adverse events. Methods: A single-group, pretest-posttest design was utilized, involving 130 participants diagnosed with HCV genotype 3. Patients received a 12-week regimen of daclatasvir (60mg daily) and sofosbuvir (400mg daily). The study conducted thorough pre-treatment and post-treatment assessments, including ELISA for HCV antibodies, PCR for viral load determination, and genotyping. Statistical analyses were performed using SPSS version 25, with significance set at p<0.05. Results: Of the 130 participants, 93% achieved SVR at 12 weeks post-treatment. The pre-treatment viral load ranged from 78,200 to 120,900,000 IU/mL, significantly decreasing post-treatment across the cohort. Genotype analysis confirmed HCV genotype 3 in 85.71% of cases. Treatment was well-tolerated, with no serious adverse events reported. Conclusion: The combination therapy of daclatasvir and sofosbuvir was highly effective and safe in treating patients with HCV genotype 3 infection, demonstrating a high rate of SVR and a significant reduction in viral load without severe adverse events. These findings support the use of this regimen as a viable treatment option for this challenging HCV genotype.

Assessment of efficacy and safety of daclatasvir, sofusbuvir and ribavirin regimen for 12 weeks as compared to daclatasvir and sofusbuvir combination regimen for 24 weeks in decompensated cirrhotic patients due to hepatitis C virus genotype 3 infection

Background: Assessment of efficacy and safety of daclatasvir+sofosbuvir+ribavirin (DCV+ SOF+ RBV) for 12 weeks as compare to daclatasvir and sofusbuvir for 24 weeks in decompensated cirrhotic patients due to hepatitis C virus (HCV) genotype 3 infection.Methods: An observational, prospective, COHORT study over 1 year, in decompensated cirrhosis due to G3-HCV infected adult patients. Treatment was a combination of sofosbuvir 400 mg/day+daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR 12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events.Results: The 32 patients were screened and 2 were excluded, one patient due to associated HBV+, one patient due to severe anemia. 30 patients were randomized. All 30 randomized patients were divided into two groups. Group 1 was given SOF+DCV+RBV for 12 weeks while group 2 patients were given SOF+DCV for 24 weeks. 81.8% of the participants in the group1 achieved SVR 12. The 90.9% of the participants in the group 2 achieved SVR12 (p=1). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed.Conclusions: Both the regimen SOF+DCV with or without RBV are highly efficacious and safe. Addition of RBV can reduce the treatment duration to 12 weeks, and it will further improve compliance and more convenient for the patients.

Effect of Atorvastatin on Single Oral Pharmacokinetics and Safety of Daclatasvir in Rats: Emphasis on P-glycoprotein and Cytochrome P450.

This study aimed to investigate the effect of atorvastatin on daclatasvir oral pharmacokinetics and safety and assess the possible underlining mechanisms by targeting P-glycoprotein (P-gp) and cytochrome P450 (CYP3A4). The transport of daclatasvir, as well as the standard rhodamine 123 by P-gp across the rat intestine, was studied in vitro using the non-everted sac method. To assess the pharmacokinetic profile of daclatasvir in vivo, rats were divided into three groups receiving either saline, standard P-gp inhibitor verapamil (25 mg/kg), or atorvastatin (10 mg/kg), 2 hrs prior to a single dose of daclatasvir (7 mg/kg). In addition, the markers of liver and kidney functions and muscle rhabdomyolysis were assessed. Further, histopathological examination of liver and kidney tissue and assessment of CYP3A4 level was done. The inhibitory effect of atorvastatin on Pgp activity and expression was manifested by increased serosal transport of the standard rhodamine 123, as well as daclatasvir. In vivo, Cmax (peak plasma concentration) and area under the curve (AUC (0-t)) of daclatasvir after atorvastatin treatment increased compared to the vehicle group but not in a significant manner. On the other hand, atorvastatin caused a significant increase in the clearance of daclatasvir. Concomitant administration of atorvastatin with daclatasvir significantly decreased CYP3A4 content compared to the control group. The combination also showed increased liver enzymes and some pathological alterations in the liver. Atorvastatin has a significant effect on P-gp mediated intestinal transport of daclatasvir; however, it did not affect the systemic bioavailability of a single oral dose of daclatasvir.

Effect of Atorvastatin on Single Oral Pharmacokinetics and Safety of Daclatasvir in Rats: Emphasis on P-glycoprotein and Cytochrome P450

Effect of Atorvastatin on Single Oral Pharmacokinetics and Safety of Daclatasvir in Rats: Emphasis on P-glycoprotein and Cytochrome P450

Real-life effectiveness and safety of the daclatasvir/asunaprevir combination therapy for genotype 1b chronic hepatitis C patients: An emphasis on the pretreatment NS5A resistance-associated substitution test.

This study aimed to investigate the real-life effectiveness and safety of daclatasvir (DCV) and asunaprevir (ASV) combination therapy in Korean patients. We consecutively enrolled patients with genotype 1b hepatitis C virus (HCV) infection treated with at least one dose of DCV/ASV combination therapy in seven tertiary hospitals of South Korea. The sustained virologic response (SVR) rates and safety according to intention-to-treat (ITT) and per-protocol (PP) analyses were evaluated. Among the 526 enrolled patients, 91% showed negative (87%) or "undetermined" (4%) resistance-associated substitution (RAS); 9% did not undergo RAS testing. The SVR rates for ITT and PP were 89.3% and 95.0% in treatment-naive patients and 93.2% and 95.6% in treatment-experienced patients, respectively. In PP analysis, negative RAS was associated with higher SVR (96.3%) than with "undetermined RAS" (85.7%) or "not tested for RAS" (84.4%). Adverse events were reported in 185 (35.4%) patients, and events leading to discontinuation were observed in 4.3% of the study population. Forty-two (8.0%) patients developed transaminase elevation (≥2 × upper normal limit), resulting in treatment discontinuation in six (1.1%) patients. DCV/ASV combination therapy showed acceptable efficacy in genotype 1b compensated HCV-infected patients with negative pretreatment RAS. Although most adverse events were tolerable to continue antiviral treatment, adequate monitoring for transaminase elevation is warranted.

Efficacy and Safety of Daclatasvir and Sofosbuvir in Egyptian Patients with Chronic Hepatitis C Genotype 4 and Cirrhosis

AbstractBackground: Hepatitis C virus (HCV) infection is a leading cause of Chronic Liver Disease (CLD) and liver transplantation globally. Currently, oral combinations of Direct Acting Anti-viral agents (DAAs) are the standard of care for treating chronic HCV infection.Aim of Study: To assess the efficacy & safety of combi-nation of Daclatasvir and Sofosbuvir in Egyptian patients with chronic hepatitis C Genotype 4 and Cirrhosis.Patients and Methods: 50 Egyptian, cirrhotic patients with HCV genotype 4 infection were treated with a generic form of sofosbuvir (SOF) 400mg, daclatasvir (DCV) 60mg with or without weight-based ribavirin (RBV) for only 12 weeks. 40 out of the 50 patients enrolled in the study, com-pleted treatment, while the remaining 10 patients were lost for follow-up.Results: The 12 weeks combination of SOF plus DCV achieved SVR in all treated patients (100%) whether treatment-naive or experienced, with or without ribavirin. A significant improvement was observed in transaminases, while a non-significant improvement was observed in serum albumin, bilirubin, INR and the mean CTP score indicating improvement in liver functions. Regarding safety outcomes, all treatment-related AEs were only minor AEs with no major AEs.Conclusion: The combination of SOF plus DCV with or without RBV for only 12 weeks is highly effective in treating HCV GT4 cirrhotic patients with SVR12 rate of 100%, safe and well tolerated by these cirrhotic patients. Moreover, there was a marginal improvement in liver functions observed 12 weeks after treatment.

High Efficacy and Safety of Flat-Dose Ribavirin Plus Sofosbuvir/Daclatasvir in Genotype 3 Cirrhotic Patients.

Background/AimsPatients with genotype 3 hepatitis C virus (G3-HCV) cirrhosis are very difficult to treat compared to patients with other HCV genotypes. The optimal treatment duration and drug regimen associated with ribavirin (RBV) remain unclear. To evaluate the efficacy and safety of daclatasvir (DCV)/sofosbuvir (SOF) plus a flat dose of 800 mg RBV (flat dose) compared to DCV/SOF without RBV or DCV/SOF plus an RBV dose based on body weight (weight-based) in G3-HCV patients with compensated or decompensated cirrhosis.MethodsWe analyzed data for 233 G3 cirrhotic patients. Of these, 70 (30%), 87(37%) and 76 (33%) received SOF/DCV, SOF/DCV/RBV flat dose, and SOF/DCV/RBV weight-based dose, respectively. Treatment duration was 24 weeks. Sustained virological response (SVR) was evaluated at week 12 posttreatment (SVR12).ResultsOverall, SVR12 was achieved in 220 out of 233 patients (94.4%). The SVR12 rate was lower in the DCV/SOF group than in the DCV/SOF/RBV flat-dose group and the DCV/SOF/RBV weight-based group (87.1% vs 97.7% and 97.4%, respectively, p=0.007). A higher incidence of anemia occurred in the DCV/SOF/RBV weight-based group compared to those in the other two groups (p<0.007).ConclusionsWe found that the DCV/SOF/RBV flat-dose regimen is an effective treatment in terms of efficacy and safety in patients with G3-HCV compensated or decompensated cirrhosis. Therefore, antiviral regimens without RBV should be restricted only to naïve patients with G3-HCV compensated cirrhosis who have a clear contraindication for RBV.

Evaluation of efficacy and safety of daclatasvir and sofosbuvir in treatment of chronic hepatitis C infection

Introduction The era of direct-acting analogs in the management of chronic hepatitis C virus (HCV) infection stared in 2011, and since then, many agents were approved for management of HCV infection. Aim To assess the efficacy and safety of daclatasvir and sofosbuvir in the treatment of chronic hepatitis C infection. Patients and methods A prospective study was done at El-Rajhi University Hospital. It included 100 patients (75 patients with chronic HCV infection and 25 patients with HCV-related compensated liver cirrhosis). They received dual therapy (sofosbuvir 400 mg plus daclatasvir 60 mg) for 12 weeks or 24 weeks for patients with chronic hepatitis C and patients with liver cirrhosis, respectively. Results Mean age of all patients was 51.48 ± 10.90 years. Overall, 64% were males, 52% were from rural areas, and 56% patients were unemployed. Sustained virological response (SVR) 12 was obtained in 98 (98%) patients included in our study, and only two (2%) patients failed to achieve sustained virological response: one patient had chronic hepatitis but took irregular course of therapy, whereas the other was a cirrhotic patient. It was noticed that 69 (69%) patients had no adverse effects during the course of therapy. Headache was the most frequent event occurred in 17 (17%) patients, comprising seven (9.3%) patients with chronic hepatitis C and 10 (40%) patients with liver cirrhosis. Conclusion This regimen of therapy has high success rate for viral eradication with minimal tolerable adverse effects.

Efficacy and Safety of Daclatasvir and Asunaprevir Combination Therapy in Elderly Chronic Hepatitis C Patients

Efficacy and Safety of Daclatasvir and Asunaprevir Combination Therapy in Elderly Chronic Hepatitis C Patients

The efficacy and safety of daclatasvir combined with asunprevir in the treatment of 26 cases with chronic hepatitis C

Objective To explore the efficacy and safety of daclatasvir (DCV) combined with asunprevir (ASV) for chronic genotype 1b (GT1b) hepatitis C. Methods Twenty-nine GT1b hepatitis C patients who were treated with DCV combined ASV in Henan Provincial People′s Hospital from September 2017 to November 2017 were included. Hepatitis C virus (HCV) RNA levels were tested before treatment, 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, 12 weeks and 24 weeks after treatment, and 12 weeks after the end of the treatment. The comorbidities, combined use of drugs and adverse clinical events were registered. T test was used to compare the measurement data with normal distribution and M (P25, P75) was used for measurement data with non-normal distribution. Results A total of 29 patients with GT1b were included, with 4 cirrhosis cases and 25 non cirrhotic cases. Seven patients had history of previous interferon and ribavirin combination treatment. There were 9 patients with comorbidity and 7 patients with combined medication. Finally, 25 patients completed a 24-week course of antiviral treatment; 3 patients were lost to follow-up, and 1 patient withdrew after 16weeks of antiviral treatment because of a virus rebound. Of the 26 followed up patients, 25 achieved sustained virological response at 12-week (SVR12), and one patient failed. And the HCV RNA NS5A resistance-associated variants (RAV) were detected in the patients with treatment failure. No severe adverse clinical events occurred in 26 patients. Conclusions DCV combined with ASV is effective and safe in the treatment of GT1b chronic hepatitis C. However, the effect of RAV on therapeutic efficacy should be concerned during the treatment. Key words: Hepatitis C, chronic; Daclatasvir; Asunprevir

Pharmacodynamic and pharmacokinetic evaluation of the combination of daclatasvir/sofosbuvir/ribavirin in the treatment of chronic hepatitis C

ABSTRACTIntroduction: The combination of daclatasvir (DCV), sofosbuvir (SOF), and ribavirin (RBV) is a direct-acting antiviral (DAA) regimen for the treatment of hepatitis C virus (HCV) infection. The inclusion of newer effective DAAs such as SOF and DCV with high efficacy and excellent tolerance introduced a new scenario in HCV infection therapy: high rates of sustained virological response (SVR), shorter therapies, less toxicity, and interferon-free treatments. This combination was approved for the treatment of HCV in treatment-naive or treatment-experienced patients with chronic HCV genotype 1 or 3 infection.Areas covered: This review summarizes the pharmacokinetics, pharmacodynamics, efficacy, and safety of DCV plus SOF and RBV therapy in the treatment of HCV infection. The topics include data regarding drug absorption, distribution, metabolism, excretion, and antiviral activity strategies, such as clinical dose selection and treatment duration.Expert opinion: This combination, taken orally with or without food, has an excellent pharmacokinetic and pharmacodynamic profile. DAC/SOF/RBV achieves very high rates of SVR in treatment-naive and treatment-experienced patients with chronic HCV infection, including difficult-to-treat patients such as those with compensated cirrhosis, post-transplant recurrence, or HIV-1 co-infection.

Daclatasvir and asunaprevir combination therapy for patients with chronic hepatitis C virus genotype 1b infection in real world.

Background/AimsPrevious studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world.MethodsWe enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end-of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure.ResultsThe mean age of patients was 59.5 ± 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure.ConclusionsDCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events.

Efficacy and safety of sofosbuvir plus daclatasvir with or without ribavirin: large real-life results of patients with chronic hepatitis C genotype 4

Clinical studies evaluating the efficacy of daclatasvir (DCV) for treatment of chronic hepatitis C virus (HCV) genotype 4 (GT4) infection are scarce. This study aims to evaluate the efficacy and safety of DCV plus sofosbuvir (SOF) with or without ribavirin (RBV) for treatment of Egyptian patients infected with HCV GT4. Between April 2016 and March of 2017, a large cohort of 946 patients with chronic HCV GT4 was enrolled for completing the treatment. Patients were classified into two groups: group 1 (easy to treat) was treated with a dual therapy of SOF/DCV daily for 12weeks and group 2 (difficult to treat) was treated with a triple therapy of SOF/DCV/RBV daily for 12weeks. Efficacy and safety of the treatments were estimated, and baseline characters associated with sustained virological response at 12weeks post-treatment (SVR12) were investigated. Among the patient's cohort, SVR12 was achieved by 94% (891/946) in the overall patients, by 95% (718/758) in the easy-to-treat group, and by 92% (173/188) in the difficult-to-treat group. The most common adverse events recorded were fatigue, headache, nausea, asthenia, and gastrointestinal troubles. No patient discontinued treatment due to severe adverse events. The findings from the present study suggested that SOF/DCV (with or without RBV) regimen exhibited high effectiveness, was well tolerated in the treatment of chronic HCV GT 4, and revealed itself as a better option for patients with advanced liver disease, making the eradication of HCV a more realistic target to achieve.

THU-377 - Real-life efficacy and safety of daclatasvir and asunaprevir therapy for genotype 1b chronic hepatitis C patients without NS5A resistance-associated substitution: A nationwide study in South Korea

THU-377 - Real-life efficacy and safety of daclatasvir and asunaprevir therapy for genotype 1b chronic hepatitis C patients without NS5A resistance-associated substitution: A nationwide study in South Korea

THE USE OF DACLATASVIR PLUS SOFOSBUVIR WITH OR WITHOUT RIBAVIRIN IN TREATMENT-NAÏVE PATIENTS WITH CHRONIC HEPATITIS C VIRUS GENOTYPE 4 INFECTION

Oral administration of dual or triple therapy is very effective in chronic hepatitis C virus infection. The current study was conducted to evaluate the effectiveness and safety of daclatasvir plus sofosbuvir with or without ribavirin in treatment-naive patients with HCV genotype 4 infection. In this study, 90 naive patients with HCV genotype 4 infection were divided into 3 groups (N=30 per each group) and randomly assigned to receive orally either daclatasvir (60 mg) plus sofosbuvir (400 mg) with or without ribavirin (800-1200 mg according to the patient’s weight) daily for 12 weeks, or sofosbuvir plus ribavirin orally and daily for 24 weeks. The primary endpoint was an HCV RNA level of < 25 IU per millilitre at week 12 (sustained virologic response at week 12, SVR12). From the current study, the males received sofosbuvir plus daclatasvir had SVR12 50%, while the females within the same group achieved SVR12 57%. Males received sofosbuvir with ribavirin achieved SVR12 85% and SVR24 94.7%, while females in the same group achieved SVR12 90.9% and SVR24 98.9 %. The highest SVR12 rates (100% in both males and females) were achieved in naive patients received the triple therapy of daclatasvir plus sofosbuvir with ribavirin. The most common adverse effects were fatigue, headache, and low haemoglobin content. Only, one female patient experienced elevated serum alanine aminotransferase (ALAT) activity after the end of the treatment. No deaths or serious adverse effects resulted in case of treatment discontinuation. In conclusion, for HCV genotype 4 infection, once-daily oral dose of the triple therapy of daclatasvir plus sofosbuvir with ribavirin for 12 weeks appears to be a very good treatment option with the lowest adverse effects and the highest SVR rates.

Daclatasvir and asunaprevir for genotype 1b chronic hepatitis C patients with chronic kidney disease

To evaluate the efficacy and safety of daclatasvir and asunaprevir combined therapy in genotype 1b chronic hepatitis C patients with non-dialysis chronic kidney disease (CKD). In a multicenter collaborative study, 249 patients received 60mg daclatasvir (NS5A inhibitor) once a day and 100mg of asunaprevir (NS3/4A protease inhibitor) twice a day for 24weeks between September 2014 and September 2015 and were subjected to this analysis. Virological response and adverse events in non-dialysis patients with CKD (stage 3-5, excluding 5D: dialysis), which was defined as estimated glomerular filtration rate <60mL/min/1.73m2 , were compared with those in patients without CKD. Overall, the rates of rapid viral response, end-of-treatment response, and sustained virological response (SVR) were 76.7%, 91.2%, and 86.3%, respectively. Among 55 patients with CKD, the rapid viral response, end-of-treatment response, and SVR rates were 76.4%, 87.3%, and 83.6%, respectively. Among 194 patients without CKD, they were 76.8, 92.3, and 87.1%, respectively. There were no significant differences in the virological response rates between the two groups (P = 0.999, 0.282, and 0.509, respectively). The baseline estimated glomerular filtration rate did not affect the achievement of SVR. The incidence of adverse events in patients with and without CKD were 21.8% and 13.9%, respectively (not significant, P = 0.142). The efficacy and safety of daclatasvir and asunaprevir combined therapy in genotype 1b chronic hepatitis C patients with non-dialysis CKD are not inferior to those in patients without CKD.

Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study.

Background/AimsThe combination of daclatasvir (DCV) and asunaprevir (ASV) has demonstrated a high sustained virologic response at 12 weeks (SVR12) and a low rate of adverse events in previous clinical studies. The purpose of this study was to clarify the results of treatment and side effects in Korean patients with chronic hepatitis C virus (HCV) genotype Ib infection.MethodsWe retrospectively analyzed clinical data from chronic HCV genotype Ib patients treated with DCV+ASV from August 2015 to September 2016 at five hospitals in the Daejeon-Chungcheong area.ResultsA total of 152 patients were examined for resistance associated variants (RAVs). Among them, 15 (9.9%) were positive for Y93 and one (0.7%) was positive for L31. Of 126 patients treated with DCV+ASV, 83 patients completed treatment and 76 patients were included in safety and efficacy analysis. Five (6.6%) were positive for Y93 and 12 (15.8%) exhibited cirrhotic change. DCV+ASV was the first-line treatment for 58 (76.3%) patients. Eleven (14.5%) patients relapsed after previous treatment that included interferon and seven (9.2%) of these patients were found to be intolerant of interferon. Adverse events occurred in 10 (13.2%) patients and two patients stopped the medication because of severe itching and skin rash. SVR12 was 89.5% (68/76) in all patients and 91.5% (65/71) in RAV-negative patients.ConclusionsDCV+ASV showed good efficacy in patients with HCV Ib infection in Korea. Close monitoring is needed for severe adverse events and treatment failure, which were uncommon.

Real-world efficacy and safety of daclatasvir and asunaprevir therapy for hepatitis C virus-infected cirrhosis patients.

Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV) infected-patients. However, the real-world efficacy and safety of the therapy for patients with cirrhosis are unknown. A total of 252 patients with genotype 1 HCV infection (158 with chronic hepatitis and 94 with compensated liver cirrhosis) were treated with 24 weeks of daclatasvir and asunaprevir combination therapy. Plasma concentrations of daclatasvir and asunaprevir at day 5 of treatment, end-of-treatment response, sustained virological response (SVR), and the frequencies of adverse events were analyzed. Plasma asunaprevir concentration was significantly higher, and daclatasvir concentration tended to be higher, in cirrhosis patients compared with chronic hepatitis patients. End-of-treatment response was achieved in 95.6% and 94.7% of chronic hepatitis and cirrhosis patients, respectively, and SVR was achieved in 94.3% and 92.6%. Although pre-treatment NS5A drug resistant-associated variants were detected, a high SVR rate was achieved when the population frequency of the variant was low. The frequencies of treatment-related adverse events in cirrhosis patients were similar to those in chronic hepatitis patients. Treatment discontinuation due to adverse events occurred in three and two patients in chronic hepatitis and cirrhosis groups, respectively; however, four out of five patients with treatment discontinuation nonetheless achieved SVR. Patients with compensated liver cirrhosis have similar virological response and tolerance for daclatasvir plus asunaprevir therapy to patients with chronic hepatitis. This combination therapy might offer a safe and effective treatment for chronic HCV infected-patients with compensated cirrhosis.

Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus-infected patients with renal impairment.

Hepatitis C virus (HCV) infection is a risk factor for end-stage renal disease, renal graft failure, and hemodialysis patient mortality. However, the efficacy of direct-acting antiviral therapy for HCV-infected patients with renal impairment is unclear. Additionally, the promising NS5B inhibitor sofosbuvir has not been recommended for patients with severe renal impairment. In this prospective, multicenter study, we evaluated the efficacy and safety of daclatasvir and asunaprevir combination therapy, with a focus on patients with renal impairment. The study included 322 genotype 1 HCV-infected patients who received daclatasvir and asunaprevir combination therapy. The safety and sustained virological response was examined at 12weeks after the end of treatment and safety was evaluated according to renal function. Of 322 patients, 5% (16/322) and 2.5% (8/322) had chronic kidney disease stage G3b (estimated glomerular filtration rate [eGFR], 30-44mL/min/1.73m2 ) and stage G4/5 (eGFR, 15-29/<15mL/min/1.73m2 ), respectively. Baseline presence of the NS5A resistance-associated variant, previous simeprevir treatment, and HCV RNA titers, which were predictors of a sustained viral response, were similar between patients with eGFR <45mL/min/1.73m2 and eGFR >45mL/min/1.73m2 . Notably, the 12-week sustained viral response rate was comparable in patients with eGFR <45mL/min/1.73m2 (100%, 24/24) and those with eGFR >45mL/min/1.73m2 (88.9%, 265/298; P = 0.07). Treatment discontinuation rates and adverse events, including alanine aminotransferase elevation, anemia, and renal disorders, were similar between the two groups. Daclatasvir and asunaprevir combination therapy for patients with renal dysfunction was highly effective and safe.

Outcomes of treatment with daclatasvir and asunaprevir for recurrent hepatitis C after liver transplantation.

The development of direct-acting oral agents has dramatically changed the treatment strategy of hepatitis C virus (HCV) infection. Here we aimed to reveal the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) for recurrent HCV genotype 1 infection after liver transplantation (LT). A retrospective study was undertaken on nine patients who underwent a 24-week DCV/ASV treatment regimen for recurrent HCV genotype 1 infection. Five of the patients were men; four had failed treatment with pegylated interferon (Peg-IFN)/ribavirin, two had failed simeprevir/Peg-IFN/ribavirin, one had the resistance-associated variant Y93H in the NS5A region, and one underwent maintenance dialysis. Median time to treatment initiation following LT was 70 months. Of the nine patients treated with DCV/ASV, eight (88.9%) achieved a sustained viral response 12weeks after completion of therapy (SVR12). The patient with virologic failure had failed simeprevir/Peg-interferon/ribavirin therapy 4months before undergoing the DCV/ASV treatment regimen. In addition, a resistance-associated variant D168E in the NS3 region was detected in the patient after discontinuation of the DCV/ASV regimen. The trough level of tacrolimus tended to decrease, and renal function showed no significant changes during treatment. Adverse events occurred in two patients (22.2%), but no severe adverse events occurred during treatment. The DCV/ASV regimen was well tolerated, resulting in high rates of sustained viral response 12weeks after completion of therapy for LT patients with recurrent HCV genotype 1 infection.