Effectiveness Of Sofosbuvir Research Articles

Effect of Sofosbuvir on rats' ovaries and the possible protective role of vitamin E: biochemical and immunohistochemical study.

Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory. Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen. However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function. It is important to evaluate the safety of SOF on the ovary, as there are no studies yet. Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility. Accumulation of SOF in the cells was demonstrated to promote ROS generation. Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility. We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies. Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated. It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction. The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed. This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.

Direct-acting antivirals sofosbuvir and daclatasvir attenuate carbon tetrachloride-induced liver fibrosis in mice

Background and aimAdvanced liver fibrosis is a major risk for developing hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) patients. Direct-acting antivirals (DAAs) which are used for treating HCV infection, produce more than 90% cure rate but do not seem to diminish the rate of occurrence or recurrence of HCC. This study aimed to investigate the effect of DAAs sofosbuvir (SOF) and daclatasvir (DAC) on carbon tetrachloride (CCl4)-induced fibrotic changes in mice. MethodsEighty adult male Swiss albino mice were randomly allocated into 8 groups (10 mice/group): normal control group, SOF group (receiving SOF 80 mg/kg body weight (BW), oral gavage, daily), DAC group (receiving DAC 30 mg/kg BW, oral gavage, daily), SOF + DAC group (receiving a combination of both, daily), CCl4 model group (receiving CCl4 2 mL/kg BW, intraperitoneal twice weekly) and three CCl4-intoxicated groups receiving either SOF or DAC or their combination. All CCl4 groups received CCl4 for 12 weeks followed by DAAs for another 12 weeks. ResultsCCl4-induced a significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and produced histopathological evidence of fibrosis and liver degeneration along with a significant increase (P ≤ 0.001) of the proliferation markers (proliferating cell nuclear antigen (PCNA) and Ki-67), hepatic stellate cells (HSCs) activation markers (alpha-smooth muscle actin (α-SMA) and glial fibrillary acidic protein (GFAP)), fibrosis marker (matrix metalloproteinase-9 (MMP-9)) and pro-inflammatory cytokine (tumor necrosis factor-alpha (TNF-α)). CCl4-intoxicated mice treated with SOF, DAC, or their combination revealed a significant amelioration (P ≤ 0.001) of CCl4-induced elevation of liver enzymes, fibrotic changes, and liver degeneration along with a significant attenuation (P ≤ 0.001) of CCl4-induced upregulation of all tested markers. The effects of SOF, DAC, and their combination on liver enzymes were comparable while the effect of SOF + DAC combination on mitigating CCl4-induced upregulation of the proliferation and HSCs activation markers was significantly stronger than either SOF or DAC alone. As for MMP-9 and TNF-α, the effects of DAC and SOF + DAC combination were comparable and both were more significant than that of SOF alone. ConclusionsSOF and DAC may possess an antifibrotic effect that is independent of their role as antiviral agents against CCl4-induced liver injury. This might exclude the role of DAAs in early occurrence or accelerated recurrence of HCC through the progression of the HCV patients' pre-existing fibrosis. However, HCC patients treated with DAAs should be closely monitored with continuous HCC surveillance during and post-therapy.

Effect of sofosbuvir and velpatasvir therapy on clinical outcome in hepatitisC virus patients with decompensated cirrhosis.

To determine the impact of direct-acting antiviral therapy on the long-term prognosis of decompensated cirrhotic patients. A total of 37 patients with hepatitisC virus-induced decompensated cirrhosis treated with sofosbuvir and velpatasvir (SOF/VEL group) were prospectively enrolled. For historical control, 65 hepatitisC virus-positive decompensated cirrhotic patients who did not receive direct-acting antiviral therapy were included (control group). The incidence rates of hepatocellular carcinoma (HCC), decompensated events with hospitalization, and overall survival were compared between both groups. A total of 41 patients experienced decompensated events during 15.0months in the control group, and six patients during 21.6months in the SOF/VEL group. The cumulative incidence rates of decompensated events after 2years were significantly higher in the control group (53.1%) than in the SOF/VEL group (14.5%; p<0.001). A total of 27 patients died within 22.0months in the control group, and three patients died within 25.6months in the SOF/VEL group. The overall survival rates after 2years were significantly lower in the control group (67.6%) than in the SOF/VEL group (91.3%; p=0.010). A total of 13 patients in the control group developed HCC during 15.8months, and 10 patients during 17.3months in the SOF/VEL group. The HCC incidence rates after 2years were 20.3% and 29.6% in the control and SOF/VEL groups, respectively, with no significant difference (p=0.327). SOF/VEL therapy may suppress the development of decompensated events and improve the prognosis in decompensated cirrhotic patients; however, the incidence of HCC remains prevalent in these patients irrespective of SOF/VEL therapy.

Effectiveness of Sofosbuvir and Velpatasvir Combination in Chronic Hapatitis C

Objective: The purpose of this research is to evaluate the efficacy of a combination medication consisting of sofosbuvir and velpatasvir in treating individuals with chronic hepatitis C. Study Design: Observational/ Prospective study Place and Duration: Conducted at Department of Gastroenterology Mayo Hospital Lahore, during from the period Feb 2021 to Jan 2022. Methods: There were 67 participants in this study. The patients' ages ranged from 18 to 70. We gathered demographic information about the patient, such as age, gender, height, and weight, after getting written consent. Hepatitis C patients with known genotypes were shown. A SOF/VLP regimen containing sofosbuvir and velpatasvir was administered to patients for a total of 12 weeks. The entire set of data was examined using SPSS 18.0. Results: In current study, 42 (62.7%) were males and 25 (37.3%). Included patients had mean age 31.12±15.80 years and mean BMI 24.7±8.34 kg/m2. We found that efficacy rate was higher and found in 63 (94.03%) cases. As per laboratory findings, aspartate aminotransferase (AST) 37.5± 11.21, alanine aminotransferase (ALT) 26.2±6.44, and haemoglobin level 12.24±10.17 all showed considerable improvement after therapy. Most common adverse outcomes were headache 35 (52.2%), fatigue 22 (32.8%) and nausea 10 (14.9%). Conclusion: In patients with or without cirrhosis, and regardless of the HCV genotype, the combination of sofosbuvir and velpatasvir has shown to be extremely successful in treating chronic HCV infection. This is true regardless of the HCV genotype. Keywords:, Hepatitis C, Sofosbuvir, Comorbidities, Velpatasvir,

Histopathological Effect of Sofosbuvir as Compared to Sofosbuvir Combined with Ribavirin on Submandibular Salivary Glands of Adult Albino Rats (Histological and immunofluorescent study)

Histopathological Effect of Sofosbuvir as Compared to Sofosbuvir Combined with Ribavirin on Submandibular Salivary Glands of Adult Albino Rats (Histological and immunofluorescent study)

Effect of sofosbuvir-based DAAs on changes in lower-density lipoprotein in HCV patients: a systematic review and meta-analysis

BackgroundPrevious studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients.MethodsA systematic review of articles published before 31 May 2021 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and non-SOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk of Bias in Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL.ResultsSix studies comprising 1248 patients were included, 848 patients treated with SOF-based DAAs and 400 patients with non-SOF DAAs vs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 than non-SOF DAAs group (P = 0.001). However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.319) did not significantly differ between the two groups. Further comparison of SOF/ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL.ConclusionsFor HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.

Histological and biochemical studies on effect of Sofosbuvir (Sovaldi) on adult male albino rat kidney

ABSTRACT Sofosbuvir (sovaldi) is the backbone of many anti‐HCV drugs. We aimed to demonstrate the effect of sofosbuvir on the adult male albino rat kidney. Sixty adult male albino rats were used. The animals were divided equally into 2 main groups (I and II), and each group was divided equally into 3 subgroups (A, B, and C). In group I (control group), each rat was gavaged 0.5 ml distilled water daily for 4 weeks. In group II (sofosbuvir treated group), each albino rat was gavaged 0.5 ml distilled water containing 7.2 mg sofosbuvir daily for 4 weeks. The rats were sacrificed at the end of the 4th week (subgroups IA and IIA), 6th week (subgroups IB and IIB), and 8th week (subgroups IC and IIC) from the start of the treatment. The kidneys were used for histological study while blood samples were used for biochemical study. The obtained data were statistically analyzed. Sofosbuvir (sovaldi) induced pathological changes that gave the criteria of acute Kidney injury in the adult male albino rats. The pathological changes were confirmed by elevation of serum level of urea and creatinine. After 2 and 4 weeks of drug withdrawal, the kidney incompletely recovered. We concluded that sofosbuvir induced criteria of acute tubular injury in the kidney of the adult male albino rats. This renal injury was proved by histological and biochemical studies. These insults were incompletely reversible after the end the treatment.

Effectiveness of Sofosbuvir and Velpatasvir Combination in Chronic Hepatitis C with Hemodialysis Patients

Objective: The aim of this study is to determine the response of sofosbuvir and velpatasvir combination in chronic hepatitis C with hemodialysis patients. Study Design: Prospective/observational study Place and Duration: The study was conducted at department of Nephrology Nawaz Sharif Kidney Hospital, Swat for duration of six months from 1st July to 31st December, 2020. Methods: Total 27 patients of both genders were presented in this study. Patients were aged between 18-85 years. Patients details demographics age, sex and body mass index were recorded after taking written consent. Patients diagnosis hepatitis C with recognized genotypes were presented. Enrolled patients received combination of sofosbuvir and velpatasvir regime (SOF/VLP) for 14 weeks and follow up was taken. Effectiveness and safety among HCV patients on hemodialysis were observed. Complete data was analyzed by SPSS 22.0 version. Results: Out of 27 patients 17 (62.96%) were males 10 (37.04%) were females. Mean age of the patients was 35.14±5.18 years with mean BMI 24.41±6.25 kg/m2. Hypertension was the most common comorbidity found in 15 (55.55%) patients followed by obesity 8 (29.63%) and diabetes found in 3 (14.81%). Among 27 cases 20 (74.04%) were naïve and 7 (25.96%) were treatment experienced. Sustained virological response was found in 26 (96.3%) and 1(3.7%) patients were lost at follow up. Significantly improvement was found in hemoglobin level 12.11 ± 5.24, alanine aminotransferase (ALT) 28.51 ± 9.62 and aspartate aminotransferase (AST) 35.24 ± 7.08 after treatment. Headache, fatigue and nausea were the most common adverse outcomes. Conclusion: We concluded in this study that the use of sofosbuvir and velpatasvir was effective safe and well tolerated in the treatment of hepatitis C patients with hemodialysis. Keywords: Hemodialysis, Hepatitis C, Sofosbuvir, Velpatasvir, Complications

EFFECTIVENESS AND SAFETY OF SOFOSBUVIR AND VELPATASVIR IN HEMODIALYSIS PATIENTS SUFFERING WITH HEPATITIS C INFECTION

BACKGROUND &amp; OBJECTIVE: There is scantiness of evidence-based knowledge of anti-viral therapy with sofosbuvir (SOF) and velpatasvir (VLP) in patients on maintenance haemodialysis. This report is an attempt to rationalise the safety and effectiveness of SOF and VLP in haemodialysis patients in Pakistan.&#x0D; METHODOLOGY: Twenty treatment-naïve patients were incorporated in this study. Patients on maintenance haemodialysis are being administered SOF and VLP. Before initiation of treatment, all necessary investigations such as viral load, liver fibro scan, genotyping and upper GI endoscopy were made. Patients received 400 mg/day and 100 mg/day dose of SOF and VLP, respectively.&#x0D; RESULTS: Mean age was 25 to 53 years; 30% were male and 70% were female as categorized. No one of these has clinical affirmation of progression of cirrhosis. The most prevalent genotype was genotype 4 that was found in 45% of cases and the second most evident was genotype 1 in 25% of cases and genotype 5 in 30% of cases. Time span of antiviral therapy was 12 weeks.&#x0D; CONCLUSION: SOF and VLP based direct antiviral agents were effectual, puissant and were aptly tolerated in patients on MHD. This drug combination was well tolerated in haemodialysis patients. Not a single patient discontinued this combination therapy due to severe complications.

Effect of Sofosbuvir (Sovaldi) on the fundic mucosa of adult male albino rats and the possible protective role of Fucoidan: Histological, histochemical, and immunohistochemical study

Background: Sofosbuvir (SOF) is a hopeful remedy for chronic hepatitis C virus infection. However, it records some unfavorable influences on gastrointestinal tract. Fucoidan is a sulfated polysaccharide having cytoprotective effect besides anti-inflammatory and antioxidant properties.Aim: This work has been focused on the possible effect of sofosbuvir on the fundic mucosa and to assess the probable role of protection of fucoidan.Materials and methods: we divided 40 adult male albino rats equally into four groups and were received drugs as a single daily dose for five weeks. Control group (I): were received distilled water and normal saline. Fucoidan group (II): were received 80 mg/kg. Sofosbuvir group (III): were received 4 mg/kg. Group IV: were received Fucoidan and Sofosbuvir with the same doses as pervious groups. All rats were sacrificed one day following the last dose. Stomach specimens were obtained and prepared for light and electron microscopic examination.Results: Sofosbuvir-treated rats showed dilated fundic pits and cystic dilatation of fundic glands with flattening of their epithelial lining. Vacuolation of cytoplasm and shrunken pyknotic nuclei were detected in parietal cells. Dilatation of rough endoplasmic reticulum and loss of secretory granules were detected in the chief cells. Infiltration of inflammatory cells with congested blood vessels and extravasated RBCs were detected in lamina propria. Statistically, there was a highly significant rise in the area% of collagen fibers while area% of Periodic Acid Schieff -Alcian Blue stain (PAS–AB) reaction showed a highly significant reduction comparing with the control. The immunohistochemical results revealed marked increase in proliferating cell nuclear antigen (PCNA) expressions. The administration of Fucoidan with Sofosbuvir minimized these changes.Conclusion: Sofosbuvir has been proved to induce histological changes in the fundic mucosa and these changes can be attenuated by Fucoidan when given in concomitant with it.

Effect of sofosbuvir plus daclatasvir on virological response and liver function tests as a line of treatment for HCV related cirrhosis (a prospective cohort study)

BackgroundPatients with chronic HCV infection are the most in need for antiviral treatment. However, patients with cirrhosis exhibit difficulty with direct antiviral agents (DAA) treatment. We intended to evaluate the virological response of DAA in HCV-related cirrhosis treatment as well as its effect on liver function tests and other laboratory tests. Our study was a prospective cohort study of 240 patients with HCV-related liver cirrhosis. Those patients were consecutively selected from Gastroenterology and Hepatology out-patient clinic at Aswan University Hospital. They were subjected to the DAA regimen (sofosbuvir 400 mg plus daclatasvir 60 mg).ResultsThe study showed a rapid decrease in HCV viral load; HCV RNA was undetectable in 65% of patients on 4th week of treatment and in 88.3% of patients on 8th week of treatment. It was undetectable in 100% of patients on 12th week of treatment and remained unchanged until therapy was completed (24 weeks). The SVR (sustained virological response) was 96.3%. Other laboratory tests demonstrated that serum level of alanine aminotransferase (ALT) decreased rapidly to normal limits on 4th week of treatment and remained within normal range until 12th week post-treatment. Significant improvements in serum albumin, total bilirubin, INR, and alpha-fetoprotein (AFP) levels were observed during and after treatment. Child-Pugh score showed a significant improvement post-treatment. We also observed a significant improvement in platelet count during and after treatment.ConclusionThe DAA regimen (sofosbuvir 400 mg plus daclatasvir 60 mg) for treatment of HCV-related liver cirrhosis can achieve satisfactory virological response (SVR more than 96%). It can lead to improvement of serum ALT, serum albumin, total bilirubin, INR, AFP, and Child-Pugh score and also increase in platelet count after treatment.

Sofosbuvir and Daclatasvir Bypassing Genotypic Investigation of Chronic Hepatitis C Infection: A Real-Life Experience at Tertiary care center in North Indian Population Sofosbuvir and Daclatasvir Bypassing Genotypic Investigation

Background and Aims: The goal of Hepatitis C Virus infection treatment is to remove the virus, to avoid advancement of Hepatitis C Virus (HCV) infection and progression of related disease such as liver cirrhosis and hepatocellular carcinoma and to achieve End of Treatment Response (ETR) with 12-week therapy and Sustained Virological Response (SVR) at post-treatment week 12 (SVR-12), which is defined as undetectable HCV RNA at 12 weeks post ETR. In the Compassionate Use Program (CUP) in Europe, Sofosbuvir (SOF) and Daclatasvir (DCV) were used in all genotypes and achieved SVR-12. Aims: Our aim is to compare the efficacy and effectiveness of Sofosbuvir and Daclatasvir in the treatment of HCV infection in the patients who could not afford for the investigating of HCVGenotype and to those in whom genotyping was done. Methods: Group 1 includes ten patients, given Sofosbuvir and Daclatasvir without genotype and group 2 includes nine patients, given Sofosbuvir and Daclatasvir with genotype. The patient group selection was done using a randomized table generated by using excel. All the patients in the groups completed the twelve weeks treatment with twelve weeks and twenty-four weeks of follow up. All the nineteen patients were given Sofosbuvir and Daclatasvir for twelve weeks and the endpoint of therapy was marked by undetectable HCV-RNA in blood by ETR-12 (end of treatment response), Sustained Virological Response at post-treatment week 12 (SVR-12) and Sustained Virological Response at post-treatment week 24 (SVR- 24). Results: Quantitative HCV-RNA (IU/ml) by RT-PCR was undetectable in all the patients in both groups at the end of treatment (ETR-12) and SVR-12- and SVR-24-weeks follow-up after completion of treatment i.e. Sofosbuvir and Daclatasvir has 100% ETR-12, SVR-12 and SVR-24 in both the groups. Conclusion: If patients do not investigate for genotype and use the Sofosbuvir and Daclatasvir in HCV infected patients, there is no effect on outcome ETR. This will reduce the risk of late stage complications such as liver cirrhosis and hepatocellular carcinoma and will also leads to the economic benefits such as no extra burden on patients.

Contrasting Role of Dose Increase in Modulating Sofosbuvir-Induced Hepatocyte Toxicity.

Sofosbuvir, the oral direct-acting antiviral, is a medication, which used as the effective treatment for hepatitis C infection. Although sofosbuvir thought to have few adverse-effects, there have been some experiences of serious drug-induced hepatotoxicity. In this research, the molecular/cellular pathways that lead to sofosbuvir-induced hepatotoxicity were evaluated on isolated rat hepatocytes. Rat hepatocytes were isolated using collagenase reperfusion technique. In evaluating the different pathways of sofosbuvir-induced hepatotoxicity, ROS formation, mitochondrial membrane potential collapse, lysosomal membrane damage, glutathione depletion, and the percentage of apoptosis versus necrosis were determined. Our data demonstrated that the cytotoxic effect of sofosbuvir in lower concentrations (25, 50 and 100 µM) is mediated by above stream pathways. On the other hand, sofosbuvir acts in opposite directions at higher concentrations (400 µM) and acts as an antioxidant and hepatoprotective. We concluded that sofosbuvir while looking toxic and pro-oxidant in lower concentrations, acts as protective and antioxidant in higher concentrations.

Effect of sofosbuvir and ribavirin therapy on hearing

Introduction An estimated 185 million people worldwide are currently infected with chronic hepatitis C virus and ∼3–4 million new infections occur each year. Sofosbuvir (SOF) administered in combination with ribavirin (RBV) resulted in high sustained virological response rates across genotype (GT) 1–6 patients. It is also the first available regimen for patients who are unsuitable for interferon. A combination of SOF and RBV was safe and well tolerated with no death or discontinuation of treatment due to adverse events. The most frequent adverse events were headache, anemia, fatigue, and nausea. Objective This study was designed to detect the effect of dual treatment with SOF/RBV on hearing and on cochlear hair cells in 50 patients with chronic hepatitis C. Subjects and methods Fifty adult male patients with chronic HCV infection and fulfilling the indications to start the medical treatment with Sovaldi, they were subjected to pre and post treatment hearing assessment by Pure Tone Audiometry (PTA) and Oto Acoustic Emission (OAEs). Results According to pure-tone audiometry, no statistically significant difference was detected in hearing threshold among patients at different frequencies, pretreatment and post-treatment. According to distortion-product otoacoustic emission (S/N), there was a highly statistically significant difference in distortion-product otoacoustic emission (S/N), at the most of frequencies in pretreatment and post-treatment. This differences confirmed (outer hair cell) damage as an ototoxic effect for SOF/RBV therapy. Recommendation Long-term follow-up to determine this effect on the outer hair cell either temporary or permanent.

Effect of sofosbuvir plus daclatasvir for treatment of chronic hepatitis C on patients with psoriasis.

Until recently, clinicians caring for patients with psoriasis who were infected with hepatitis C virus (HCV) were concerned that treating one condition could exacerbate the other. We evaluated the outcome of treatment with direct-acting antiviral agents (DAAs) on patients with psoriasis having chronic hepatitis C (CHC) infection. This was an observational prospective cross-sectional study. It included CHC-naive patients with plaque psoriasis. All patients received sofosbuvir plus daclatasvir once daily for 12 weeks for treatment of CHC. Psoriasis area severity index (PASI) scores and the dermatology quality-of-life index were evaluated at the start of treatment with DAAs and then at 12 and 24 weeks after the end of HCV treatment. The primary end point was sustained virological response 12 weeks after treatment (SVR12). A total of 34 CHC-naive patients were enrolled in this study. Most of them were of male sex (76.5%), and most of them had severe psoriasis, as the mean PASI score was 32. The primary and secondary end points (SVR12 and SVR24) for our patients were 100%. Regarding PASI and dermatology quality-of-life index scores, there was a highly significant difference before start of treatment and after treatment at 12 and 24 weeks. The most common adverse events are fatigue and headache. Sofosbuvir plus daclatasvir is effective in the eradication of HCV and improvement of symptoms in patients with psoriasis having CHC infection. Future large series studies are needed to evaluate this promising effect of DAAs.

Effect of sofosbuvir on QT interval and other electrocardiography (ECG) findings in patients with HCV related decompase cirrhosis

Effect of sofosbuvir on QT interval and other electrocardiography (ECG) findings in patients with HCV related decompase cirrhosis

Effect of sofosbuvir and daclatasvir on lipid profile, glycemic control and quality of life index in chronic hepatitis C, genotype 3 patients.

The management of hepatitis C has progressed from interferon-based therapy to oral direct actingantiviral therapy. Deranged lipid levels (total cholesterol, triglyceride) after treatment with interferon-based therapy are well known. There is a paucity of data on changes in lipid profile, glycemic parameters and alteration in quality of life with the newer regimen. This study was designed to assess the changes in lipid profile, glycemic parameters, quality of life in chronic hepatitis C patients with genotype 3 after treatment with sofosbuvir and daclatasvir. The study was a single-centre, prospective study, conducted at tertiary care hospital from January 2017 to December 2017. Fifty patients, who received sofosbuvir (400mg) and daclatasvir (60mg) orally once daily for a period of 12weeks for chronic hepatitis C and genotype 3, were recruited. Total cholesterol levels (166.9 ± 23.8to 192.4 ± 34.5mg/dL, p-value < 0.0001) and low-density cholesterol (LDL) levels (100.9 ± 22.8to 121.6 ± 37.2, p-value < 0.0001) were elevated after the treatment. A significant decrease in median levels of glycated hemoglobin (HbA1c) was observed (5.57% to 5.41%, p-value < 0.002). Quality of life markedly improved in all domains, i.e. physical, physiological, environmental, andsocial relationships according to an abbreviated form of World Health Organization quality of life assessment namedWHOQOL-BREF questionnaire. Treatment was found to be effective with sustained virological response (SVR) achieved in 94% patients. Our study reports a substantial increment in total cholesterol, andlow-density lipoprotein with sofosbuvir and daclatasvir treatment though it achieved SVR in 94% of patients and improved their quality of life.

Efficacy and Adverse Effects of Sofosbuvir plus Daclatasvir Therapy in Chronic HCV Patients in Sharkia Governorate, Egypt

Background and study aim: Hepatitis C is the most pressing public health challenge in Egypt with variable prevalence rates among different age groups. This study aimed to detect the efficacy and adverse effects of sofosbuvir plus daclatasvir therapy in treatment of chronic HCV patients in Sharkia governorate. Patients and Methods: One hundred and ten patients were included in this study, divided into 4 groups; group I: 55 treatment naive patients receiving (sofosbuvir + daclatasvir) for 12 weeks, group II: 36 treatment naive patients receiving (sofosbuvir + daclatasvir +ribavirin) for 12 weeks, Group III: 9 treatment experienced patients receiving (sofosbuvir + daclatasvir + ribavirin) for Session [UserIDID] weeks and Group IV: 10 chronic HCV patients not receiving anti-viral therapy. Patients were followed by clinical and laboratory evaluation monthly during treatment and for 3 months after end of treatment. In addition, the virological response and adverse effects were reported. Results: The rate of SVR response was equal in the three treated groups. There was statistically significant increase in nausea and headache in groups I and II while arthralgia, myalgia and fatigue were more frequent in group I. There was also statistically significant improvement in Child score among treated cirrhotic patients after treatment. Conclusion: Daclatasvir plus sofosbuvir with or without ribavirin for 12 or Session [UserIDID] weeks is highly effective in treatment of naive or experienced Egyptian HCV patients in Sharkia governorate. This combination is well tolerated in both cirrhotic and non-cirrhotic patients with mild adverse effects.

Effectiveness of Sofosbuvir and Ribavirin for Eradicating Hepatitis C Virus in Renal Transplant Recipients in a Resource Constrained Country

Effectiveness of Sofosbuvir and Ribavirin for Eradicating Hepatitis C Virus in Renal Transplant Recipients in a Resource Constrained Country

Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveal Bradycardiac Effects Caused by Co-Administration of Sofosbuvir and Amiodarone.

Co-administration of sofosbuvir, an anti-hepatitis C virus medication, and antiarrhythmic amiodarone causes symptomatic severe bradycardia in patients and animal models. However, in a few in vitro studies, the combination of sofosbuvir and amiodarone resulted in tachycardiac effects in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This discrepancy may be attributable to the use of immature hiPSC-CMs in the in vitro studies. To address this, we evaluated the ability of our in-house hiPSC-CMs to assess the interactions between sofosbuvir and amiodarone in vitro. We performed whole-cell patch recordings on hiPSC-CMs to examine the cardiac effect of sofosbuvir and amiodarone, alone or in combination. We found that sofosbuvir and amiodarone caused bradycardiac effects (the beating rate decreased to 75% of the vehicle control, P < 0.001) on our hiPSC-CMs when applied in combination, but they had no significant effect when applied alone. Furthermore, the bradycardiac effect was membrane potential dependent: it increased with depolarization. This raised the possibility that the bradycardiac effects in vivo may originate in nodal cells, which have a more depolarized resting membrane potential compared with ventricular cells. The bradycardiac effects of sofosbuvir plus amiodarone in vitro are consistent with the clinical phenotype and suggest that our hiPSC-CMs may serve as a useful tool in assessing cardiac safety during drug discovery and development process.