Sofosbuvir-daclatasvir Research Articles

Sofosbuvir, Velpatasvir and Voxilaprevir for Treatment of Chronic Hepatitis C Virus Patients Non-Responder to Previous Sofosbuvir-Daclatasvir Therapy

Abstract Background Egypt is one of the countries with a high HCV burden; the percentage of HCV antibody positivity is 4.61 % of Egyptian general population. The advent of oral direct-acting antivirals (DAAs), as a treatment for chronic hepatitis C (CHC), has revolutionized the field with obvious safety and efficacy privileges. Despite the high rates of SVR achieved with DAAs, HCV is not eliminated from a considerable proportion of patients (1-15%). So, a new problem has emerged which is the need for re-treatment of patients who couldn’t be cured with DAAs in the first instance. Aim of the Work to evaluate the efficacy of sofosbuvir, velpatasvir, voxilaprevir for previously DAA-(Sofosbuvir–Daclatasvir)-treated Egyptian patients who failed to achieve SVR after their treatment. Patients and Methods This study was performed in Ahmed Maher Teaching Hospital, Cairo, Egypt, Internal Medicine Department. The study included 139 patients with chronic hepatitis C Non- responder to Previous Sofosbuvir-Daclatasvir Therapy. Patients enrolled in the study were prospectively evaluated as outpatients by the study staff at 4, 8, 12 weeks and at 12 weeks post-treatment. All the patients were subjected to history taking, clinical examination, complete biochemical and virological studies. Results The overall treatment outcome: there was a statistically highly significant difference in PCR before treatment (100%+ve) and after treatment (97.1%-ve) 3 month after treatment. Throughout the study, most of the patients were responders (97.1% achieved SVR 12). Conclusion Rescue therapy with SOF/VEL/VOX is safe and highly effective, for treatment of chronic hepatitis C virus patients non-responder to previous Sofosbuvir-Daclatasvir therapy achieving SVR12 rates 97.1%.

Efficacy and safety of DAA in children and adolescents with chronic HCV infection: A systematic review and meta-analysis.

We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines. We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach. A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes. CRD42020146752.

Budget impact analysis of two treatment approaches for hepatitis C in Malaysia through the use of voluntary and compulsory licensing options.

A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to sofosbuvir/daclatasvir (SOF/DAC) is available through compulsory licensing, with access to sofosbuvir/velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes but has higher drug acquisition costs compared to SOF/DAC. A stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications. The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years. A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.

Predictors of Treatment Failure with Sofosbuvir/Daclatasvir Regimen for 12 Weeks in Patients with Chronic HCV in Egypt

Background: Hepatitis C virus HCV infection is one of the main causes of chronic liver disease worldwide, Egypt has the highest national-level HCV prevalence in the world, Sofosbuvir/ Daclatasvir (SOF/DAC) regimen widely used to treat HCV infection in Egypt.&#x0D; Aims: to identify the predictors of treatment failure with Sofosbuvir/Daclatasvir regimen for 12 weeks in HCV Egyptian patients.&#x0D; Methodology: A retrospective cohort, we investigated the predictors of treatment failure in 2300 HCV patients received the SOF/DAC regimen in Egypt.&#x0D; Results: Patients who completed the treatment and follow up visits were 2079 patients,4 patients stopped treatment due to side effects, 35 due to incompliance and 182 patients missed their follow up visits after treatment, out of the 2079 patients 2043 (98.3%) patients responded to treatment with SVR12 and just 36 (1.7%) patients had treatment failure, presence of Hypertension (p=0.001), Diabetes Miletus (p=0.001), ALT level &gt;51 (p=0.013) , AST level &gt;60 (p=0.002), AFP &gt; 6 (p=0.000) and abnormal liver echo-pattern all were found to have an impact on SVR12 rates, some other factors were found to be insignificant as age, sex, BMI, special habits, liver function tests, haemoglobin, total leucocytic count and serum creatinine, by multivariate analysis AFP was found to be the strongest predictor of treatment failure with cut off value &gt;6 with sensitivity 66.67% and specificity 77.31%.&#x0D; Conclusion: This study shows that ALT, AST, AFP, Abnormal Liver Echo-pattern and the Presence of Diabetes Miletus or Hypertension were found to affect SVR rates, but the strongest predictor was AFP level with a cutoff value of &gt;6.

Pangenotypic Hepatitis C Therapy with Direct Acting Antivirals: A Southern Nigeria Pilot Experience

Background: Viral hepatitis C (HCV) is a global health challenge affecting at least 3.3% of the world population. Sub-Saharan Africa still battles with under diagnosis, and poor access to diagnostic facilities occasioned by a lack of manpower/facilities to treat infected persons bringing about an increase in HCV-associated morbidity and mortality. The goal of this prospective observational study is to assess the efficacy of sofosbuvir/daclatasvir (SOF/DAC) combination as a pangenotypic treatment for hepatitis C without HCV genotype determination in patients with hepatitis C attending the hepatology clinic at the Rivers State University Teaching Hospital (RSUTH).&#x0D; Method: One hundred and fifty (150) HCV RNA positive patients were enrolled into the study. Their sociodermographic factors, clinical and laboratory parameters including pre and post treatment HCV RNA were assessed. Treatment eligible patients received sofosbuvir 400mg and daclatasvir 60/90mg for 12 weeks which was extended to 24 weeks in patients with decompensated liver disease. Treatment success was defined as undetectable HCV RNA 12 weeks after completion of therapy (SVR-12).&#x0D; Results: One hundred and nine (109) of the 150 recruited patients were eligible for treatment. The male to female ratio of the study population was 1.1:1(79, 52.7%):71,49.3%) with a mean age of 47.78±13.39 years. Eighty-six (86,78.9%) of the 109 treated patients had undetectable HCV RNA at SVR-12 and this was most likely to occur in patients with low viremia (OR=2.52, 95%CI=0.985-6.436, p=0.050). Extension of treatment duration played no apparent role in the achievement of SVR-12 (SVR-12=33.3%), however, previously treated HCV patients had a better outcome.&#x0D; Conclusion: Sofosbuvir/ daclatasvir pangenotypic therapy is effective for treatment of HCV patients without genotyping.

Metabolic changes in chronic hepatitis C patients receiving direct acting antivirals

Background: Treatment of chronic hepatitis C (CHC) with direct acting antivirals (DAAS) improves the rates of sustained virological response (SVR). However, derangements with lipid profile and glycemic status have been observed. This study aimed to compare the effect of sofosbuvir/daclatasvir (SOF/DAC) versus sofosbuvir/ledipasvir (SOF/LED) regimens on metabolic status of CHC patients. Methods: An observational prospective study was conducted on a total of 140 easy-to-treat treatment-naïve genotype-4 chronic hepatitis C virus (HCV) infected Egyptian patients. Patients received either 400 mg SOF/60 mg DAC or SOF 400 mg/90 mg LED daily for 12 weeks. Patients were followed-up for 12 weeks after end-of-treatment. Total lipid profile, fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) were measured at baseline, four weeks (during treatment), and 12 weeks post-treatment (24 weeks). Clinical laboratory tests and treatment side effects during the treatment period were assessed to ensure safety. Complete blood picture, liver function tests, fibrosis-4 index (FIB-4) were performed at baseline and week 12. Results: Both groups had 100% SVR. In both groups, no significant difference in body mass index was found after treatment. FIB-4 decreased significantly after treatment in the SOF/LED group. Regarding lipid profile, total cholesterol (TC) and low-density lipoproteins (LDL) were significantly increased then slightly decreased between week four and week 24 respectively in both groups with higher percentage change in the SOF/LED group. On the other hand, high-density lipoprotein (HDL) decreased throughout the follow-up period in both groups with no significant difference between two groups. Regarding glycemic status, HbA1c and FBS were significantly decreased in both groups throughout the study period with significant difference in the percentage change of HbA1c and FBS between two groups. Conclusions: SOF/LED regimen showed a significant change in lipid profile parameters more than the SOF/DAC regimen, while both regimens showed favorable outcomes in HbA1C and FBS levels.

Economic evaluation of pan-genotypic generic direct-acting antiviral regimens for treatment of chronic hepatitis C in Iran: a cost-effectiveness study

IntroductionLow-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent...

Cost-utility Analysis of Second-generation Direct-acting Antivirals for Hepatitis C

Background: Hepatitis C virus (HCV) can lead to increased mortality, disability, and liver transplantation if left untreated, and it is associated with a possible increase in disease burden in the future, all of which would surely have a significant impact on the health system. New antiviral regimens are effective in the treatment of the disease yet expensive. Objectives: The purpose of the present study was to assess the cost-effectiveness of three medication regimens, namely, ledipasvir/sofosbuvir (LDV/SOF), velpatasvir/sofosbuvir, and daclatasvir/sofosbuvir (DCV/SOF) for HCV patients with genotype 1 in Iran. Methods: A Markov model with a lifetime horizon was developed to predict the costs and outcomes of the three mentioned medication therapy strategies. The final outcome of the study was quality-adjusted life-years (QALYs), which was obtained using the previously published studies. The study was conducted from the perspective of the Health Ministry; therefore, only direct medical costs were estimated. The results were provided as the incremental cost-effectiveness ratio (ICER) per QALY. Ultimately, the one-way and probabilistic sensitivity analyses were used to measure the strength of study results. Results: The results showed that the QALYs for LDV/SOF, DCV/SOF, and VEL/SOF were 13.25, 13.94, and 14.61, and the costs were 4,807, 7,716, and 4,546$, respectively. The VEL/SOF regimen had lower costs and higher effectiveness than the LDV/SOF and DCV/SOF regimens, making it a dominant strategy. The tornado diagram results showed that the study results had the highest sensitivity to chronic hepatitis C (CHC) and compensated cirrhosis (CC) state costs. Moreover, the scatter plots showed that the VEL/SOF was the dominant therapeutic strategy in 73% of the simulations compared to LDV/SOF and 66% of the simulations compared to DCV/SOF; moreover, it was in the acceptable region in 92% of the simulations and below the threshold. Therefore, it was considered the most cost-effective strategy. Moreover, the results showed that DCV/SOF was in the acceptable region below the threshold in 69% of the simulations compared to LDV/SOF. Therefore, the DCV/SOF regimen was more cost-effective than LDV/SOF. Conclusions: According to the present study results, it is suggested that the VEL/SOF regimen be used as the first line of therapy in patients with HCV genotype 1. Moreover, DCV/SOF can be the second-line medication regimen.

Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience

Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles. Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed. ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree. ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.

Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia.

Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.

Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment

PurposeThis systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical...

The Efficacy and Safety of Sofosbuvir/Daclatasvir Fixed-Dose Combination in Iranian Hemodialysis Patients with Hepatitis C Virus Infection

Background: Although several regimens have been approved for the treatment of hepatitis C virus (HCV) infection, sofosbuvir-based regimens are not approved for the treatment of HCV infection in patients with severe renal impairment. Methods: This study was conducted on hemodialysis patients infected with HCV. The patients received a constant dose of sofosbuvir/daclatasvir (SOF/DCV). Sustained virologic response (SVR) was evaluated 12 weeks after completion of treatment. Results: Fifty-one hemodialysis patients with HCV infection were selected and treated with a combination of SOF/DCV. Eleven patients expired during the anti-HCV treatment due to causes not related to liver disease or antiviral therapy. Finally, 40 patients finished the treatment, and 36 cases were evaluated for SVR. Among those tested for SVR, 35 (97.2%, 95% CI: 85.5 - 99.9%) achieved SVR and one (2.8%, 95% CI: 0.1 - 14.5%) relapsed. No patient reported severe adverse events. Conclusions: The combination of SOF/DCV showed great efficacy and safety in hemodialysis patients with severe renal impairment and chronic HCV infection.

Role of optical coherence tomography angiography in detecting possible retinal vascular complications of sofosbuvir and daclatasvir in patients with hepatitis C virus infection

Purpose The aim of this study was to evaluate the value of optical coherence tomography angiography (OCTA) in the detection of any suspected retinal complications associated with the use of combined therapy (sofosbuvir ‘Sovaldi’ and daclatasvir ‘Daklinza’) in patients with hepatitis C virus infection. Patients and methods This is a prospective cohort study that enrolled patients with chronic hepatitis C who did not receive any previous antiviral treatment and who were candidates for the dual therapy. During a 3-month duration (the treatment course duration), OCTA was performed for documented chronic hepatitis C-infected patients before and after receiving the dual therapy (daclatasvir–sofosbuvir). The minimum outcome measures were best-corrected visual acuity and vascular density by OCTA macula. Results There was a statistically significant reduction in the deep capillary plexus (P≤0.05). The whole macular vessel density was reduced from 51.56 to 47.68% after the treatment course (P=0.04). These vascular density changes were associated with statistically insignificant increase in thickness. In addition, the choriocapillaris had a statistically significant reduction in flow area from 2.145 to 2.063 mm2 (P=0.0001). The superficial capillary plexus changes in vessel density were statistically insignificant except at the temporal parafoveal area. There was also a statistically significant reduction in the foveal avascular zone flow density from 54.42% before starting the dual therapy course to 51.85% after finishing it (P=0.022). These changes were associated with a statistically significant reduction in best-corrected visual acuity from 0.83 to 0.63 (P&lt;0.001) and a statistically significant development of macular drusen (P=0.004). Conclusions Hepatitis C virus dual treatment (sofosbuvir and daclatasvir) may result in significant changes affecting the retinal microvasculature.

Efficacy and Tolerability of Daclatasvir/Sofosbuvir (Datex) in Patients with HIV-HCV Co-infection

Background: Treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents in patients with HCV/human immunodeficiency virus (HIV) co-infection remains controversial due to drug interactions with antiretroviral therapy (ART). Objectives: In this study, we assessed the efficacy and tolerability of daclatasvir/sofosbuvir (DCV/SOF) in patients with HIV-HCV co-infection in the real-life setting in Iran. Methods: A total of 44 patients with HCV-HIV co-infection (genotypes 1, 3, and 4) were treated with DCV/SOF±RBV (ribavirin) (dose-adjusted DCV for concomitant ART). Assessment of risk factors, sustained virologic response at 12 weeks after the end of treatment (SVR12), safety, and serum CD4 count was performed. Results: Most patients were male (95.2%). Four patients were HCV treatment-experienced cases, and 15 had cirrhosis or advanced fibrosis. The most common genotype was 3 (53.5%), followed by 1 (44.2%) and 4 (2.3%). HIV-1 RNA &lt; 50 copies/mL and CD4 count &gt; 250 cells/mm3 were observed in 81.8% and 79.1% of patients, respectively. The highest risk factor was a history of IV drug use (81.8%), followed by using a common syringe (77.3%) and tattooing (70.5%). All patients with or without cirrhosis (100%) completed the HCV treatment course and achieved SVR12. Also. 92.6% of patients on ART had CD4 count &gt; 250 cells/mm3 at the end of treatment. The HCV treatment regimen was well-tolerated. Moreover, 15.9% of patients experienced adverse events (AEs), including anorexia, nausea, diarrhea, palpitations, and anxiety. No serious AEs or discontinuation due to AEs were reported. Conclusions: Our study showed excellent tolerability and efficacy of DCV/SOF±RBV in HIV-HCV co-infected patients with or without cirrhosis.

Daclatasvir/Sofosbuvir versus Ledipasvir/Sofosbuvir in Patients with Hepatitis C Virus Infection Genotypes 1 and 3

Background: The new direct-acting antiviral agents (DAAs) with high efficacy, low resistance, and low rate of adverse events (AEs) have shown promising outcomes for hepatitis C virus (HCV) treatment. This study assessed the efficacy and safety of Daclatasvir/Sofosbuvir (DCV/SOF) compared to Ledipasvir/Sofosbuvir (LDV/SOF) in patients with HCV infection in the real-world setting in Iran. Materials and Methods: A total of 42 patients with HCV infection were treated with either LDV/SOF (genotype 1) or DCV/SOF (genotypes 1, 3 or unknown) with or without ribavirin (RBV). Assessment of risk factors, laboratory tests, sustained virologic response at post-treatment week 12 (SVR12), and AEs were performed. Results: The highest risk factor for HCV transmission was major surgery (50.0%), followed by tattooing (40.5%), phlebotomy (40.5%), and dental surgery (40.5%). No statistically significant relationships between genotypes and risk factors were observed. In both treatment groups (LDV/SOF and DCV/SOF), all of the patients (100%) with or without cirrhosis and treatment-experience achieved SVR12. One patient with a history of failed LDV/SOF therapy achieved SVR12 following retreatment with DCV/SOF. Both treatment regimens were well-tolerated. No serious AEs or discontinuation due to AEs was observed. The most common AE across both treatment groups were fatigue (42.9%), followed by anxiety (28.6%). Numerically, more adverse events were found with the LDV/SOF regimen than with the DCV/SOF regimen. Conclusion: Our study showed an excellent safety and efficacy of DCV/SOF and LDV/SOF in Iranian patients infected with HCV. The incidence of AEs among patients treated with LDV/SOF was higher than those receiving SOF/DCV.

Follow-up of chronic paediatric hepatitis C virus in a low-/middle-income country.

Follow-up of chronic hepatitis C virus (HCV) infection following Interferon (IFN) plus Ribavirin (RBV) or direct-acting antiviral (DAA) drug therapy in a cohort of paediatric outpatients as confirmed by a sustained virologic response (SVR). This study included a cohort of 60 patients (6-18years), divided into 2 groups: Group 1:21 patients who completed treatment with IFN/RBV. Group 2:39 treated with dual DAA therapy: 19 with Sofosbuvir/Ledipasvir (SOF/LED) and 20 with Sofosbuvir/Daclatasvir (SOF/DCV). Group 1:12 (57.1%) were cured, six were IFN/RBV treatment failure then subsequently treated with DAAs successfully, and three had liver transplants. IFN/RBV side effects were reported in all patients; however, fibrosis regressed in two cured patients. Group 2: all were cured. HCV RNA became negative in all DAAs-treated patients at weeks 2, 4 and 12 of treatment (100%) as well as SVR after 12weeks (100%). Thirty patients reported no adverse side effects whereas only nine suffered minor side effects. In our cohort, SOF/LED therapy and SOF/DCV therapy were extremely safe and effective with 100% SVR and negligible short-term side effects. IFN/RBV therapy was much less effective (SVR 57.1%) and accompanied with short-term side effects. Fibrosis might stop and even regress with successful treatment.

Effectiveness of sofosbuvir based direct-acting antiviral regimens for chronic hepatitis C virus genotype 6 patients: Real-world experience in Vietnam.

Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice. We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections. 1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46-64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3-6.6 versus 6.3, 5.3-6.5 log10 IU/ml, p = <0.001, Mann Whitney U test). A sustained virological response (SVR), defined as an undetectable viral load measured between 12 and 24 weeks after completing treatment, and indicating cure, was seen in 97.3% (1711/1758) of patients. Treatment failure, defined as HCV viral load ≥15 IU/ml ≥12 weeks after completing treatment appeared to be more frequent in patients infected with genotype 6 virus (3.2%, 37/1148) than in those infected with genotype 1 (1.7%, 10/610), p = 0.050 chi-squared test). We found no evidence that patient's age, gender, liver cirrhosis, diabetes, HBV or HIV coinfection, prior treatment failure with pegylated interferon therapy, body mass index (BMI), aspartate aminotransferase to platelet ratio index (APRI), or fibrosis 4 (FIB-4) index were associated with treatment failure. Our study suggests that patients with HCV genotype 6 infection in Vietnam may respond less well to treatment with sofosbuvir based DAAs than patients with genotype 1 infections. Further studies are needed to confirm this observation and to define whether it is driven by genotype-specific mutations.

Effect of Hemodialysis on Efficacy and Pharmacokinetics of Sofosbuvir Coformulated with Either Daclatasvir or Ledipasvir in Patients with End-Stage Renal Disease

Background/Aims: Direct-acting antivirals (DAAs) play a key role in the eradication of hepatitis C virus (HCV) infection. However, limited data are available on DAA for treating HCV infection in hemodialysis (HD) patients. This study was to evaluate the pharmacokinetic characteristics and effectiveness of daclatasvir/sofosbuvir (DAC/SOF) and ledipasvir/SOF (LDV/SOF) in HD patients. Methods: Seven patients were given SOF coadministered with DAC or LDV once daily for 12 weeks. The plasma concentrations of SOF007, DAC, and LDV were determined by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. Results: A sustained virologic response in week 12 (SVR12) was achieved in 6 (100%) patients, except for 1 patient dying due to severe cerebral hemorrhage not related to antiviral therapy. The extraction ratio of SOF007 was 66.67%, and the estimated HD clearance of SOF007 was 5.65 L/h. Conclusion: The combination of SOF with either DAC or LDV is well tolerated and offers high SVR12 in HD patients.

Changes in renal function indices in chronic hepatitis C patients treated with sofosbuvir/daclatasvir, with or without ribavirin

Abstract Background Hepatitis C virus HCV infection is one of the main causes of chronic liver disease worldwide, Egypt has the highest national-level HCV prevalence in the world, Sofosbuvir/Daclatasvir (SOF/DAC) regimen widely used to treat HCV infection in Egypt. Aim of the Study to assess changes in renal indices during and after HCV treatment in chronic hepatitis C patients treated with sofosbuvir/daclatasvir, with or without ribavirin with normal baseline creatinine Methods This study was a real life data analysis which recruited a number of “509” patients who received (SOF/DAC) regimen for 12 weeks with or without ribavirin in New Cairo viral Hepatitis Treatment Center, one of the NCCVH specialized centers. According to Supreme Council and NCCVH Hepatitis C Updated Treatment Protocol included patients received either: Sofosbuvir (400mg) + Daclatasvir (60mg) for 12weeks orSofosbuvir (400mg) + Daclatasvir (60mg) + Ribavirin for 12weeks. All data for chronic HCV patients who treated with sofosbuvir /daclatasvir, with or without ribavirin with normal baseline creatinine and achieved SVR,were compared to assess changes in renal indices during and after HCV treatment Results At the end of treatment, the estimated glomerular filtration rate (eGFR) level was significantly decreased and the serum creatinine( Scr) levels were significantly increased compared with baseline levels (eGFR: 91.63 ± 26.41 vs 85.71 ± 24.86, P01 &amp;lt; 0.001; Scr: .87 ± .20 vs.92 ± .22, P01 &amp;lt; 0.001and no significant improvements were observed at 24 w post-treatment (eGFR: 89.65 ± 26.14vs 91.63 ± 26.41 ,P02 = 0.029; Scr: .89 ± .24. vs 87 ± .20, P02 = 0.020. Considering the difference in liver conditions, changes in renal function indices were compared between cirrhotic patients and non-cirrhotic patients. At the end of treatment, cirrhotic patients and non-cirrhotic patients had decreased eGFR levels and increased Scr levels at 24 w post-treatment, the eGFR and Scr levels were significantly improved in non-cirrhotic patients, while no obvious improvements were observed in cirrhotic patients. Conclusion Although DAAs are highly effective and well tolerated, at the end of treatment we found that: The eGFR level was significantly decreased and the Scr levels were significantly increased compared with baseline levels and no significant improvements were observed at 24 w post-treatment.Both Cirrhotic patients and non-cirrhotic patients had decreased eGFR levels and increased Scr levels at 24 w post-treatment but the eGFR and Scr levels were significantly improved in non-cirrhotic patients , while no obvious improvements were observed in cirrhotic patients.

Comparative study between the efficacy of using sofosbuvir/daclatasvir and sofosbuvir/ledipasvir in treatment of hepatitis C virus in Egypt

Background Hepatitis C virus (HCV) infection is a global health care problem, with more than 170 million people infected worldwide. With the discovery of new direct-acting antiviral drugs, a new hope to get HCV cure has arisen. This work was designed to compare the efficacy between the use of sofosbuvir (SOF)/daclatasvir (DCV) and SOF/ledipasvir (LDV) in treatment of HCV. Patients and methods A total of 430 patients were enrolled into two groups: SOF/DCV group included 340 patients and SOF/LDV group included 90 patients. Each patient received treatment for 12–24 weeks. All patients were checked at each visit (at weeks 4, 8, 12, and 24) for the potential adverse events by a check-list questions, examinations, and laboratory tests. Check-list questions include headache, gastric upset, skin rash, and sleep disturbance. Results A total of 419 (97.4%) patients achieved sustained virologic response (SVR), and only 11 (2.5%) patients failed to achieve SVR. In SOF–DCV, 97.4%, and in SOF–LDV, 97.8% achieved SVR. Minor adverse events were mainly headache, sleep distribution, gastrointestinal tract disturbance, and skin rash, which were observed in 13.8% of patients in SOF–DCV group 20% in SOF–LDV group. Conclusion The use of the two regimens SOF/DCV and SOF/LDV yielded high success ratio for viral eradication with minimal tolerable adverse effects. These regimens of therapy have a great margin of safety with high efficacy.