Combination Of Daclatasvir Research Articles

Safety and Efficacy of Directly Acting Antivirals (Sofosbuvir & Daclatasvir) in Treatment of Chronic HCV

Abstract Background The introduction of direct-acting antiviral agents, has revolutionized the treatment for chronic HCV with higher cure rates, shorter duration of treatment and more tolerability have been achieved. Aim of the Work The aim of our study is to estimate the efficacy and safety of DAAs in treatment of chronic HCV in patients co-infected with HIV. Patients and Methods This study of previously untreated HCV infection in patients with HCV and HIV co-infection conducted at Abbasia Fever Hospital, from July 2019 to February 2020. Patients included are chronic HCV infection and were receiving antiretroviral therapy for the HIV with a CD4 T-lymphocyte count of 200 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed during treatment by combination of daclatasvir 90mg and sofosbuvir 400mg+/- ribavirin 800mg daily for 12 weeks. Results In this study, the rate of a sustained virologic response (SVR) at post-treatment week 12 (SVR 12) were high (29/30, 96.67%). The most common adverse events were fatigue (73.33%), headache (46.67%), and there was a high safety profile on using DAAs. No patient discontinued treatment because of adverse events. No serious adverse events or mortality were reported. In this study, AST & ALT were significantly decreased at end of treatment and 12 weeks after treatment, CD4 count was significantly increased. Otherwise there are no significant changes in both hematological and biochemical laboratory results. Conclusion Combination of daclatasvir and sofosbuvir have showed 96.67% sustained virologic response at 12 weeks after treatment (SVR 12) among HIV/HCV co-infected patients, with a very good safety profile. Moreover, the treated patients showed a significant increase in CD4 count. Accordingly, HIV/HCV co-infected patients should be treated with sofosbuvir and daclatesvir containing regimens.

Comparison of thrombomodulin, vWF, and ADAMTS13 levels between preeclampsia and normal pregnancy

To determine and compare plasma thrombomodulin, von Willebrand factor and von Willebrand factorcleaving protease levels between pre-eclamptic and healthy pregnant females. The cross-sectional, comparative study was conducted at the Department of Haematology, University of Health Sciences, Lahore, Pakistan, from November 2019 to December 2020, and comprised pregnant females who were divided into healthy pregnant group A and pre-eclamptic group B. Plasma thrombomodulin and von Willebrand factor-cleaving protease levels were determined by using commercially available enzyme-linked immunosorbent assay kit, and von Willebrand factor level was determined by using immuno-turbidimetric assay kit. Data was analysed using SPSS 25. Of the 88 participants, there were 44(50%) females with mean age 25.5±6 years in group A and 44(50%) in group B with mean age 26±5 years. Median thrombomodulin level in group B was significantly higher than group A (p=0.003). Median von Willebrand factor-cleaving protease levels were lower in group B compared to group A (p=0.838). A significant difference in von Willebrand factor level was observed between the groups (p=0.038). Females with pre-eclampsia had significantly higher plasma levels of von Willebrand factor and thrombomodulin than healthy pregnant subjects.

Predictive Potential Of Il28b Gene In Hcv Patients, Resistant To Daclatasvir And Sofosbuvir In KPK Population.

Recently various combinations of direct acting antivirals (DAAs) have been tried successfully. The Sofosbuvir + Daclatasvir combination has been used with promising results. Recently, resistance has been noticed against DAAs. Therefore, polymorphism at particular sites in the interleukin 28B gene are under study to find possible association with resistance. This study was aimed at finding out any association of SNPs rs8099917 and rs12979860 (IL28B gene) with response and resistance to treatment in HCV genotype 3 patients in Khyber Pakhtunkhwa. This cross sectional, Analytical study was conducted at Gastroenterology/hepatology OPD of Prime Teaching Hospital, Peshawar Medical College. Collected Samples were stored at -20o C in PCR Lab of the College. DNA extraction and genotyping was carried out at BJ Molecular Biology Lab in Rawalpindi. Data was analyzed by using SPSS version 21. Chi-Square Test was used to see the statistically significant differences between rs8099917 T/G and rs12979860 T/C model. In the IL28-B gene, single nucleotide polymorphism at rs12979860 T/C model, we observed that there are 37.5% CC homozygous, 12.5% TT homozygous and 50% CT heterozygous genotypes in resistant patients and 42.85% CC homozygous, 28.57% TT and 28.57% CT genotype in responder group. In rs12979860 T/C model, genotype of IL28-B in the responder and resistant group significantly varies at p-value =0.00572. We conclude that in SNP at rs12979860, CC genotype is associated with clearance of HCV, while CT genotype was more prevalent in the resistant group and associated with chronicity.

Usefulness Of Sofosbuvir And Daclatasvir Combination In The Treatment Of HCV Infection In Childhood Cancer Patients: Experience From A Tertiary Care Hospital.

To determine the usefulness of Sofosbuvir-Daclatasvir combination in the treatment of hepatitis c virus infection in paediatric cancer.. The retrospective study was conducted at the Oncology Department of the National Institute of Child Health, Karachi, and comprised medical charts of patients who received sofosbuvir and daclatasvir from January 2018 to January 2022. Efficacy was documented by clearance of hepatitis C virus ribonucleic acid as rapid viral response, early viral response and sustained viral response at weeks 4, 12 and 24, respectively. Drug efficacy was determined by monitoring and recording adverse effects. Chemotherapy protocol for the treatment of patients concomitantly receiving direct acting antivirals was modified while looking at drug-drug interactions. The total duration of direct acting antiviral therapy was 12 weeks. Data was analysed using SPSS 24. Of the 804 patients with different malignancies, 132(16.4%) were found positive for hepatitis C virus. Of them, 28(21.21%) patients were started on direct acting antivirals; 17(60.71%) boys and 11(39.28%) girls. The overall mean age was 9.93±6.12 years. The diagnosis was pre-B acute lymphoblastic leukaemia in 18(64.28%) cases, 16 (57.14%) were on maintenance chemotherapy, and 18(64.28%) had genotype 1. Pre- and post-treatment mean alanine transaminase levels were 328.00±324.00IU and 36.00±29.00IU, respectively (p=0.003). Pre- and post- treatment mean serum bilirubin levels were 3.13±3.95mg/dl and 0.61±0.21mg/dl (p=0.022). Rapid viral response was achieved in 26(92.85%) children, while early viral response and sustained viral response were achieved in all 28(100%) patients. Minor side effects were noted in 4(14.28%) patients and chemotherapy was continued in all 28(100%) cases as per the designed protocol. The sofosbuvir-daclatasvir combination was found to be effective in hepatitis C virus treatment in paediatric cancer patients.

Cardiovascular Risk Assessment After Sofosbuvir And Daclatasvir Regimen For Chronic Hepatitis C Virus Infection.

To assess cardiovascular risk after sofosbuvir and daclatasvir antiviral combination therapy in chronic hepatitis C virus patients. The prospective cohortstudy was conducted at the Kafrelsheikh University Hospital, Egypt, from December 2019 to December 2021, and comprised adult patients of either gender with chronic hepatitis C virus and with minimum ejection fraction 40%. They were classified into groups according to their cardiovascular risk. Group 1 had individuals with no risk factors, Group 2 had patients with many risk factors, Group 3 had patients with only hypertension, Group 4 had those with diabetes alone, and Group 5 comprised smokers. All the patients were evaluated for the risk of major cardiovascular events at baseline and at the end of 12-week of antiviral combination therapy of sofosbuvir 400 mg once daily dose and daclatasvir 60 mg once daily dose. Data was analysed with SPSS version 23. Of the 200 patients, there were 96(48%) males and 104(52%) females. The age ranged 34-81 years. There were 78(39%) patients in Group 1; 20(25.6%) males and 58(74.4%) females with mean age 54.4±10.45 years. Group 2 had 60(30%) patients; 40(66.6%) males and 20(33.3%) females with mean age 59.57±9.1 years. Group 3 had 25(12.5%) patients; 3(12%) males and 22(88%) females with mean age 61.4±7.8 years. Group 4 had 13(6.5%) patients; 10(77%) males and 3(23%) females with mean age 55.4±10.4 years. Group 5 had 24(12%) patients who were all (100%) males with mean age 60.7±5.7 years. There were non-significant changes in the incidence of angina, arrhythmias or progression of dyspnoea (p>0.05). Echocardiography follow-up results showed non-significant changes in mean ejection fraction, global longitudinal strain and pulmonary artery pressure (p>0.05). Sofosbuvir and daclatasvir combination therapy wasfound to be safe in chronic hepatitis C virus patients regarding cardiac risks.

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.

Safety and Efficacy of Ledipasvir/Sofosbuvir in HCV genotype 1 infection and the combination of Sofosbuvir and Daclatasvir in HCV genotype 3 infection in India

Safety and Efficacy of Ledipasvir/Sofosbuvir in HCV genotype 1 infection and the combination of Sofosbuvir and Daclatasvir in HCV genotype 3 infection in India

STABILITY INDICATING HPLC METHOD FOR SOFOSBUVIR AND DACLATASVIR IN COMBINATION

Direct acting fixed dose combination of sofosbuvir and daclatasvir to treat the viral hepatitis C disease is available in the market. So, a precise and robust stability indicating HPLC method for sofosbuvir and daclatasvir was developed. The SunQ C18 column (250 x 4.6 mm) was used for chromatographic separation with mobile phase consisting of 0.03 mM potassium dihydrogen phosphate buffer (pH 7): ACN (50: 50V/V). Optimised method satisfies the system suitability parameters with good resolution with 4.9 min Rt of sofosbuvir and 7.6 min Rt of daclatasvir. The method was validated as per ICH guidelines. Linearity was observed over range of 10-50 (µg mL-1) and 2.25-11.25 (µg mL-1) for sofosbuvir and daclatasvir, respectively. Both drugs were subjected to various stress conditions and high recovery values were found for daclatasvir on photolytic stress. The degradation was more on oxidative and hydrolytic stress for sofosbuvir. This optimised method offers new insight towards stability studies of both drugs.

Assessment of auditory function in hepatitis “C” patients managed by combination of sofosbuvir and daclatsavir

BackgroundTo evaluate the effect of daclatasvir and sofosbuvir on auditory function in hepatitis C patients. Thirty hepatitis C virus (HCV) patients were included in this study with age ranged from 22 to 55 years. All patients underwent full audiological evaluation before beginning and after completion of their treatment with combination of daclatasvir and sofosbuvir.ResultWhen the results of audiological data were compared before and after treatment, we found that; there were statistically significant differences in the pure tone audiometry (PTA) threshold and ART bilaterally mainly in the high frequency region. Transient evoked otoacoustic emission (TEOAE) reproducibility showed a statistically significant difference bilateral. However, there was no statistically significant difference in the Auditory Brainstem Response (ABR) findings.Conclusion and recommendationsThe combination therapy of daclatasvir and sofosbuvir used in patients with HCV led to deterioration in the hearing threshold in the basic audiological tests (PTA and immitancemetry). In addition, it had an adverse effect on the cochlear OHCs, with no affection on auditory nerve, brain stem functions or in sub-thalamic function, it seems that it had no effect, we cannot confirm. The study evaluate hearing at the end of treatment immediately. We recommend performing a routine monitoring of auditory functions in HCV patients treated with daclatasvir and sofosbuvir combination by specialist for early detection of auditory changes to avoid further damage to auditory system.

Determination of the Efficacy of Daclatasvir Plus Sofosbuvir in Patients with Acute ‎Respiratory Coronavirus Syndrome (SARS-COV-2): A Randomized Clinical Trial

Background: To tackle the 2019 coronavirus infection (COVID-19) disease pandemic, effective antiviral therapy is critical. We assessed the efficacy of sofosbuvir and daclatasvir for treating patients with COVID-19.
 Methods: This was a randomized controlled trial in adults with moderate-to-severe COVID-19 disease admitted to Razi Teaching Hospital in Ahvaz, Khuzestan Province, Iran. Patients were randomly assigned to the sofosbuvir and daclatasvir group (n=35, intervention group) and control group (n=35, standard care). The primary endpoint of this study was the length of hospital stay, clinical improvement, mechanical ventilation, mortality, and side effect.
 Results: We found that the combination of Daclatasvir and Sofosbuvir (DCV+SOF) did not make a statistically significant difference in terms of mortality. There was no significant difference in the duration of hospitalization between the two groups. The two groups did not differ significantly in terms of the frequency of side effects. There were 2 cases of intubation and death in both groups.
 Conclusion: The medications used in this study, i.e, the combination of daclatasvir and sofosbuvir, failed to show a significant effect in patients, and despite promising laboratory studies, there were no improvements observed in vital signs and the indicators studied, including clinical signs. Hospitalization days, ventilator requirements and mortality did not make a significant difference. To confirm the results of this study, conducting researches with a larger sample size are needed.

Efficacy of Sofosbuvir, Daclatasvir and Ribavirin Combination Therapy in Treatment Naïve Hepatitis C Patients at Tertiary Care Hospital of South Punjab

Introduction: Hepatitis C has gradually become endemic in Pakistan, with infectivity rates one of the highest in the world. The emergence of direct acting antivirals (DAAs) has become a ray of sunshine in eradicating this menace from this region. The combination of sofosbuvir, daclatasvir and ribavirin (SOF/DACLA/RIBA) has had phenomenal success all over the world in eradicating this virus. Our study aims to see the effectiveness of this regime in this part of the world. Methods: After approval from the institutional review board (IRB), retrospective analysis of data of treatment naïve patients who have been treated with the above mentioned regimen was collected to assess the efficacy by calculating the sustained virological response (SVR) at 12 weeks after completion of therapy. Results: Data of 300 patients (172 females, 128 males) was collected. Mean age was 39.66 years. Majority (almost 90%) of patients were from District Multan Age range was from 18 years to 60 years. Eighty-three percent of the patients were non-cirrhotics, 15.7% had compensated cirrhosis, while only 1 % had decompensated cirrhosis. Out of the 300 patients, 291 patients had undetectable HCV RNA on polymerase chain reaction (PCR) at 12 weeks after completion of treatment, achieving SVR rates of 97%. There was no significant association of SVR rates with gender and age of patients. Conclusion: The combination of SOF/DACA/RIBA is highly efficacious for treatment of hepatitis C patients. Keywords: sofosbuvir, daclatasvir, efficacy, sustained virological response, hepatitis C

Efficacy of sofosbuvir and daclatasvir in compensated chronic hepatitis C infection

Aims and objectives: The advent of directly acting agents for the treatment of Hepatitis C infection has forever transformed our understanding and management of viral infections. With over 95 % patients achieving a sustained viral response at 12 weeks with some of these newly inducted agents, the prospect of eradicating the Hepatitis C virus seems like an achievable target, which makes this one of the most important discoveries in modern medicine. We studied the combination of Sofosbuvir and Daclatasvir in patients with chronic hepatitis C infection (Genotype 3) to assess the rates of sustained virological response at 12 weeks. Methods: We studied 67 treatment naive patients with compensated chronic hepatitis C infection (genotype 3). They were all started on Tab Sofosbuvir 400 mg daily and Tab Daclatasvir 60 mg once daily for 12 weeks and followed up for a total of 24 weeks, which includes a treatment duration and observation period of 12 weeks each. The patients were monitored with HCV RNA levels at one, three and six months, with as many evaluations of liver function and routine hemogram.

Efficacy of Daclatasvir with Sofosbuvir for Treating Chronic Hepatitis C Genotype 3

Objective: To determine efficacy of Daclatasvir with sofosbuvir in treating patients of chronic hepatitis C genotype 3. Study Design: Interventional case-series study Place and Duration of Study: Hepatitis Clinic, Medical Unit–II, Jinnah Hospital, Lahore from January 2019 to June 2019. Methodology: One hundred and thirty five patients of chronic hepatitis C Genotype 3 were enrolled. All patients were givendaclatasvir60mg and sofosbuvir 400mg once-daily for 12 weeks. HCV-RNA-PCR was done at end of 12 weeks of treatment (ETR) and 12 weeks after end of treatment (SVR). Results: The mean age of the patients was 49.8 ±2.3 years. There were 57.7% males while 42.2% females with 22.2% frequency of cirrhosis in them.The mean value of AST and ALT was calculated as 57.07 ± 48.69 and 51.02 ± 44.17 IU/ml respectively in hepatitis C patients having genotype 3.The treatment follow up showed that on reassessing the hepatitis C status through quantitative analysis of genotype 3 through PCR it was seen that 91.1% patients reached SVR with no viral detection in them. Conclusion: Daclatasvir in combination to sofosbuvir is an efficient way of treating hepatitis C patients suffering from genotype 3. Keywords: Viral load, Sofosbuvir, HCV, Genotype 3

Three Smart and Original Spectrophotometric Data Processing Ratio Techniques for Resolving the Partial Overlapped Spectra of the Binary Antiviral Mixture Daclatasvir/Sofosbuvir: Application to Combined Dosage Form Darvoni® Tablets.

The combination of daclatasvir (DCV) and sofosbuvir (SFV) is now widely used as an ideal treatment for hepatitis C virus (HCV) infection. For this purpose, simple, sensitive, rapid, and smart spectrophotometric methods were developed and validated for the determination of these drugs in their combined dosage form. Development of smart, sensitive, low-cost spectrophotometric methods for the determination of DCV and SFV in their combined dosage form. Ratio subtraction (RS), amplitude modulation (AM), and mean-centering spectrophotometric methods were established and validated for the estimation of SFV in the presence of DCV without previous separation, using a unified regression equation. A linearity range of 2.5-25.0 µg/mL was confirmed for the direct measurement of DCV at 316 nm (because there is no interference from SFV. Linearity was confirmed over a concentration range of 10.0-80.0 µg/mL for SFV. The current methods were established according to the ICH recommendations, and specificity was examined by testing synthetic mixtures of both drugs. They were tested on their tablet dosage form, and a good recovery was obtained. The current methods proved to be simple, specific, and economical. A statistical study of the current ratio approaches and published methods showed there was no apparent statistical variation. Both antiviral agents can be quantified in the presence of each other by the current methods, which is a significant time- and cost-saving benefit of the developed methods. This benefit is even more important in the case of the combined dosage form (Darvoni® tablets) for the pharmaceutical market.

Assessment of Renal Function in Egyptian HCV Patients Treated with Combination Therapy of Sofosbuvir and Daclatasvir

BACKGROUND: According to the most recent Egyptian demographic health census, the estimated Hepatitis C virus (HCV) prevalence in the 15–59 age range was 14.7%. Globally, the incidence of renal impairment in HCV-positive individuals is 40% higher than in HCV-negative patients. HCV-induced renal impairment can range from mild-to-severe, and it frequently complicates the treatment outcome of HCV infection. AIM: This study aimed to explore the changes in renal function in Egyptian HCV patients treated with a combination of Sofosbuvir (SOF) and Daclatasvir (DCV). METHODOLOGY: Six hundred and eleven chronic HCV patients treated with SOF-DCV were enrolled. Patients were classified into three groups according to their baseline renal function: unimpaired group (estimated glomerular filtration rate [eGFR] ≥ 90 ml/min/1.73 m2), mildly impaired group (eGFR of ≥60–89 ml/min/1.73 m2), and moderately impaired group (eGFR of ≥30–59 ml/min/1.73 m2). Every month during treatment and at 24 weeks after treatment (sustained virological response 24), the eGFR level was evaluated. RESULTS: Our findings indicated that the eGFR level was significantly increased (p < 0.001) in all groups during the treatment but subsequent decline (p < 0.001) in all groups was documented after 6 months of treatment. Multivariate analysis identified baseline renal impairment (<90 ml/min/1.73 m2, p < 0.001) and baseline anemia (p < 0.001) as independent risk factors for renal function deterioration at the end of treatment. CONCLUSION: Clinical physicians should closely monitor renal function in patients treated with SOF-DCV. Furthermore, anemia therapy prior to SOF-DCV treatment should be recommended.

Successful treatment of hepatitis C genotype 4 using sofosbuvir, daclatasvir, simeprevir and ribavirin in Egyptian patients with direct-acting antiviral agent treatment failure.

IntroductionIn chronic hepatitis C virus (HCV) patients in whom prior direct-acting antiviral agent (DAA) treatment had failed, outcomes after retreatment are optimal. Combination of sofosbuvir (SOF), daclatasvir (DCV), simeprevir (SIM), and ribavirin (RBV) in treatment experienced patients is recommended in current guidelines despite insufficient data. Our aim is to determine the efficacy and safety of SOF, DCV, SIM plus RBV in HCV infected patients who failed prior DAA treatment.Material and methodsOne hundred and seventeen patients who failed to respond to SOF containing regimens were randomized according to previous response to therapy to non-responders and relapsers. Duration of therapy depends on fibrosis stages. SOF, DCV, SIM and weight based RBV 12 weeks for F1 and F2 (group I) and 24 weeks for F3 and F4 (group II).ResultsIn the non-responder group, a sustained virologic response (SVR) occurred in 100% in group I (F1 and F2) and 97% in group II (F3 and F4). Relapse was 3% in group II (F3 and F4). No patients from either group had breakthrough or non-response. In relapsers SVR was 100% in group I (F1 and F2) and 96% in group II (F3 and F4). Breakthrough, relapse and non-response were 2%, 4%, 2% respectively only in group II (F3 and F4).ConclusionsCombining multiple DAAs with different viral targets may be effective treatment protocol in previous non-responders and relapsers with short durations of treatment.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BackgroundThe combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19.MethodsThis was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1.ResultsBetween July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95–1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77–1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality.ConclusionsWe observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Hepatocellular Carcinoma in Hepatitis C-Associated Cirrhotic Patients Treated with Different Combinations of Direct-Acting Antiviral Agents Available in Pakistan: A Prospective Observational Study

Background: The hepatitis C virus (HCV) is a leading cause of chronic liver disease, including hepatic cirrhosis and hepatocellular cancer (HCC). Drugs that act directly on the virus, like as direct-acting antivirals (DAAs), are associated with improved long-term virologic responses and reduced treatment time. Pakistani patients with HCV-related cirrhosis receiving DAA medication were studied to see if they had an increased risk of hepatocellular carcinoma (HCC). Material and Methods: We conducted a prospective observational study at Isra University Hospital Hyderabad from July 2019 to August 2020. Three hundred fourteen patients met the inclusion criteria and were included. We recorded baseline demographic characteristics, Child-Pugh class, model for end-stage liver disease (MELD) score, alpha-fetoprotein level, and abdominal ultrasound/computed tomography (CT) scan before and after treatment. Results: Three hundred-fourteen individuals took part in the research. The average age of participant with hepatocellular carcinoma was 46.7 years. Twenty (sixty-nine) of the participants developing hepatocellular carcinoma were men, while nine (thirty-one percent) were women (p=0.221). Five (17.2%) of the HCC participants were diabetics, and seventeen (58.6%) were tobacco users (p=0.001). Twenty individuals (69%) developed HCC after receiving a combination of sofosbuvir and daclatasvir. A sofosbuvir/velpatasvir combination led to the development of HCC in nine (31%) of individuals (p=0.1). HCC was diagnosed in eight individuals under the age of forty (27.6%), but in 21 patients beyond the age of forty (72.6%) (p=0.55). HCC was found in 65.6 percent of Child-Turcotte-Pugh class A participants. Conclusion: DAAs have been linked to a higher risk of HCC. Participants receiving a combo of sofosbuvir/daclatasvir were more likely to develop HCC than those who received sofosbuvir/velpatasvir alone. Keywords: Velpatasvir, Hepatocellular carcinoma, Sofosbuvir, Cirrhosis,

Safety &amp; Efficacy of Directly Acting Antivirals (Sofosbuvir &amp; Daclatasvir) in Treatment of Chronic HCV in HIV-HCV Co-Infected Egyptian Patients

Abstract Background The introduction of direct-acting antiviral agents, has revolutionized the treatment for chronic HCV with higher cure rates, shorter duration of treatment and more tolerability have been achieved. Objectives The aim of our study is to estimate the efficacy and safety of DAAs in treatment of chronic HCV in patients co-infected with HIV. Patients and Methods This study of previously untreated patients with HCV and HIV co- infection conducted at Abbasia Fever Hospital, from July 2019 to February 2020. Patients included those who are chronic HCV infection and receiving antiretroviral therapy with a CD4 T-lymphocyte count of 200 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed during treatment by combination of daclatasvir 90mg and sofosbuvir 400mg+/- ribavirin 800mg daily for 12 weeks. Results In this study, AST &amp; ALT were significantly decreased at end of treatment and 12 weeks after treatment, CD4 count was significantly increased. Otherwise there are no significant changes in both hematological and biochemical laboratory results. The demographic features of the patients and HIV disease characteristics were not predictors of HCV treatment failure. Conclusion More studies on larger numbers of patients are required for proper evaluation of the safety and efficacy of direct acting antiviral agents generally and sofosbuvir plus daclatasvir combination particularly in HIV/HCV coinfected patients. Longer follow-up studies are still recommended to fully understand the impact of sustained virological response on dynamics of liver fibrosis, biochemical profile and rate of relapse.

Impact of Hepatitis C Virus Eradication Following Direct Acting Antivirals on Liver Stiffness Measurement

Abstract Background Hepatitis C infection is a disease with significant global impact, about 130150 million people chronically infected with the hepatitis C virus (HCV), representing about 2-2.5% of the world’s population. In Egypt, the prevalence is 10% and according to the last DHS in 2015 it was 7%. Aim of the Work to evaluate the effect of SVR using DAAs on the stage of the liver fibrosis in HCV patients by measuring of liver stiffness, using transient elastography before and after receiving treatment. Patients and Methods This study was conducted in co-operation between Gastroenterology and Hepatology Department, AinShams University and the Gastroenterology and Hepatology Department, Theodor Bilharz Research Institute between January 2019 to September 2019. It included 103 adult Egyptian patients who received SOF/DAC for three months and were assessed before and after achieving SVR-24. The patients were recruited from the outpatient clinic of Theodor Bilharz Research Institute Hospital (after consents were obtained). Results study showed that achieving SVR-24 was associated with improvement of LSM assessed by Transient Elastography and application of FIB-4 score and overall improvement of liver biochemistry as shown by reduction of AST, ALT and serum bilirubin and increase of serum albumin, INR and platelets. This was accompanied by increase of hemoglobin, Creatinine and BMI. The study also showed despite the fact that results were accompanied by significant improvement in LSM, Fib-4 and liver biochemistry, achieving SVR did not guarantee improvement of cirrhosis; only 29% of cirrhotics regressed to sub-cirrhotic range (LSM &amp;lt;12.5 kPa). Conclusion Sofosbuvir / Daclatasvir combination is effective and well tolerated for treatment of genotype 4 chronic hepatitis C patients. Achieving SVR-24 was associated with significant improvement of LSM using transient elastography to assess liver fibrosis. Achieving SVR-24 was associated with overall improvement of liver biochemistry. Improvement of LSM was more in cirrhotic patients than non-cirrhotic patients.