Treatment Of Chronic HCV Infection Research Articles

Real-World Effectiveness and Safety of Direct-Acting Antivirals in Patients with Chronic Hepatitis C and Epilepsy: An Epi-Ter-2 Study in Poland.

In Poland, active HCV infection affects between 0.4 and 0.5% of the population, i.e., about 150,000 people, while the number of patients with epilepsy is estimated to be 350,000-400,000. Currently available antiviral therapies show little interaction with neurological drugs. The aim of our study was to evaluate the effectiveness and safety of the treatment of chronic HCV infection in patients with coexisting epilepsy. A total of 184 epilepsy patients were selected from the group of 10,152 HCV-infected patients treated for HCV infection within the Epiter-2 database from 2015 to 2018. Comparing the effectiveness and safety of anti-HCV regimens between the patients with comorbid epilepsy and 3573 patients without comorbidities was our study's objective. The effectiveness of anti-HCV treatment was high in both the sample and the control group. No statistically significant SVR difference was observed between the sample group, with ITT = 93.5% and mITT = 95.5%, and the control group, with ITT = 95.2% and mITT = 97.5%, regardless of the genotype and the stage of liver disease at the start of therapy. The treatment was safe in patients with epilepsy. The effectiveness and safety of HCV treatment in patients with epilepsy are comparable to those of patients with no significant comorbidities.

Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom.

Background: Donor hepatitis-C (HCV) infection has historically represented a barrier to kidney transplantation (KT). However, direct-acting antiviral (DAA) medications have revolutionised treatment of chronic HCV infection. Recent American studies have demonstrated that DAA regimes can be used safely peri-operatively in KT to mitigate HCV transmission risk. Methods: To formulate this narrative review, a comprehensive literature search was performed to analyse results of existing clinical trials examining KT from HCV-positive donors to HCV-negative recipients with peri-operative DAA regimes. Results: 13 studies were reviewed (11 single centre, four retrospective). Outcomes for 315 recipients were available across these studies. A sustained virological response at 12 weeks (SVR12) of 100% was achieved in 11 studies. One study employed an ultra-short DAA regime and achieved an SVR12 of 98%, while another achieved SVR12 of 96% due to treatment of a missed mixed genotype. Conclusion: HCV+ KT is safe and may allow increased utilisation of organs for transplantation from HCV+ donors, who often have other favourable characteristics for successful donation. Findings from US clinical trials can be applied to the United Kingdom transplant framework to improve organ utilisation as suggested by the NHSBT vision strategy “Organ Donation and Transplantation 2030: meeting the need”.

ՔՐՈՆԻԿ ՎԻՐՈՒՍԱՅԻՆ C ՀԵՊԱՏԻՏ. ՀԱԿԱՎԻՐՈՒՍԱՅԻՆ ԲՈՒԺՄԱՆ ՓՈՒԼԵՐԸ (ՎԵՐԼՈՒԾՈՒԹՅՈՒՆ)

All over the world, liver diseases occupy a significant place among the causes of disability and mortality, particularly, in patients with chronic liver lesions, which are common in people of working age. Chronic hepatitis C has a special place among liver diseases. A distinctive feature of chronic HCV infection is its long-term latent course due to which it remains unrecognized for a long time. At the same time, it gradually progresses with further development of liver cirrhosis and/or hepatocellular carcinoma. WHO estimates that about 290,000 people died from hepatitis C in 2019, mostly as a result of cirrhosis of the liver or hepatocellular carcinoma. In the 90s of the twentieth century, recombinant interferons were used in mono mode, dosages were selected, treatment periods were increased, and the significance of HCV genotypes and viral load was established in predicting the results and duration of treatment. In the late XX – early XXI centuries, pegylated interferons (PIFN-α-2a and PIFN-α-2b) began to be introduced into clinical practice. The use of these drugs in combination with ribavirin made it possible to make a qualitative breakthrough in the treatment of chronic HCV infection. The WHO updated guidelines released in 2018 recommend therapy based on pangenotypic direct-acting antiviral drugs, which guarantees treatment for almost all patients with chronic hepatitis C. It is important that treatment be initiated before the patient develops liver cirrhosis and/or hepatocellular carcinoma.

The Efficacy and Safety of Treatment of Chronic HCV Infection by Ombitasvir/Paritaprevir/Ritonavir with Ribavirin and its Effect on Complement C3 and C4 Levels

The Efficacy and Safety of Treatment of Chronic HCV Infection by Ombitasvir/Paritaprevir/Ritonavir with Ribavirin and its Effect on Complement C3 and C4 Levels

Application of different spectrophotometric methods for quantitative analysis of direct acting antiviral drugs simeprevir and sofosbuvir

Simeprevir and sofosbuvir are direct-acting antiviral drugs approved for the treatment of chronic HCV infection. Reports demonstrate the similarities between HCV and SARS-CoV-2 in terms of structure and replication mechanism. Therefore, it is suggested that a combination of simeprevir and sofosbuvir may be considered for COVID-19 patients. To date, no spectrophotometric methods have been published for quantitative analysis of simeprevir and sofosbuvir in combination. In this work, two simple spectrophotometric methods allowed quantitative analysis of the studied drugs in the mixed form. The zero-order direct method allowed quantitative analysis of simeprevir at 333 nm, with sofosbuvir showing zero absorbance values. The dual wavelength method allowed quantitative analysis of sofosbuvir by measuring the difference in absorbance values at 259.40 and 276 nm, where the difference in absorbance values of simeprevir was zero. With the applied methods, the investigated drugs in the mixtures and tablets prepared in the laboratory were successfully analyzed quantitatively with acceptable results.

Echocardiographic assessment of ventricular function in chronic HCV patients receiving direct antiviral therapy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hepatitis C virus (HCV) infection is still a major public health burden in many parts of the world (1). Globally, an estimated 58 million people have chronic hepatitis C virus infection, with about 1.5 million new infections occurring per year (2). Treatment for chronic HCV infection has evolved from interferon (IFN)-based therapy to direct-acting antivirals (DAAs) (3,4). With the development of DAA, treatment of HCV became better-tolerated and highly effective (5,6). Several studies have attempted to explore their cardiac side effects, especially their impact of left ventricular (LV) function; however, these studies were limited by their design and the methods of assessment (7-10). Aim In this prospective study we aimed at evaluating the short effects of DAAs on left ventricular functions using 3D Echocardiography. Methods Patients with HCV infection planned to receive combination therapy of Sofosbuvir 400 mg daily plus Daclatasvir 60 mg daily for 12 weeks were assessed by echocardiography before starting and after 3 months after completion of treatment. Patients with other systemic or cardiac conditions or structural heart disease were excluded. Assessment of LV volume and EF was performed by 3D quantification and global longitudinal strain (GLS). Right ventricle size was assessed by 2D and systolic function was evaluated by TAPSE, S` and FAC. Results In 102 patients who were followed up at 3 months after DAA therapy, We found an increase in increase in both LV end diastolic dimensions and volumes (p∼0.02 & p∼0.045 respectively) as well as end systolic volumes (p∼0.005). There was no significant difference in neither LV systolic function as assessed by EF and GLS (62.25 ± 5.15 vs. 62.35 ± 5.77, p∼0.850, -22.97 ± 2.93 vs. -22.83 ± 2.59, p∼0.546 respectively), nor in diastolic function (p∼0.546). However, subgroup analyses revealed a significant negative correlation between age and GLS (P∼0.022) as well as the number of cardiovascular risk factors (P∼0.039). Hypertension was found to be the only predictor of the decrease in GLS in the regression analysis of risk factors (p∼0.001). There was no significant change in RV size and systolic function at follow up. Conclusions There was no significant change in LV systolic or diastolic function before and after DAA therapy as measured by EF and GLS. Nonetheless, subgroup analysis suggests a drop in GLS in older patients and those with more cardiovascular risk factors. An increase in LV size was also noted while no significant effect was noted with regards to RV size and function.

Efficacy, safety and feasibility of treatment of chronic HCV infection with directly acting agents in hematopoietic stem cell transplant recipients – Study of infectious diseases working party of EBMT

ObjectivesLimited data is available on HCV directly acting agents (DAAs) in haematopoietic stem cell transplant (HSCT) recipients. This study aimed at reporting the characteristics, treatment practices and treatment efficacy in HSCT recipients with chronic HCV. MethodsProspective observational study from EBMT Infectious Diseases Working Party (IDWP). Patients with chronic HCV infection were included. ResultsBetween 12/2015 and 07/2018, 45 patients were included: male in 53%; median age 49 years (range, 8–75); acute leukaemia in 48.9%, lymphoma in 17.7%, non-malignant disorders in 22.3%; allogeneic HSCT in 84%; 77.8% no immunosuppressive treatment. Genotypes 1, 2, 3 and 4 were detected in 54.5%, 20.5%, 13.6% and 11.4%, respectively; advanced fibrosis in 40%, including cirrhosis in 11.4%. Overall, 37 (82.2%) patients received DAAs, at a median of 8.4 years after HSCT (16.2% within 6 months from HSCT). Sofosbuvir-based treatment was given to 62.2%. Thirty-five patients completed planned treatment course, with sustained virological response (SVR) of 89.1%, and 94.3% (33/35) in those who completed the treatment. Side effects possibly related to DAAs were reported in 5 (14%) and did not require treatment discontinuation. ConclusionsDAAs treatment was effective, safe and feasible in this cohort of mainly allogeneic HSCT recipients with mild/moderate liver damage.

Treatment of Chronic HCV Infection with Direct Acting Antivirals

Objectives: This study was conducted to discover the treatment outcome and side effects of chronic hepatitis C virus patients treated with Direct-Acting Antivirals (DAAs). Methods: Based on the Liver Center database, we studied the treatment effect of Sofosbuvir 400 mg/Ledipasvir 90 mg in 1109 patients with chronic hepatitis C virus infection during the time period from December 2015 to December, 2018. Results: In patients treated with Sofosbuvir/Ledipasvir, the sustained viral load (SVR12) was 97.9% (1086/1109) 12 weeks after the treatment. The SVR12 was 99.2% (845/851) in HCV-infected non-cirrhotic patients, 93.4% (241/258) in patients with cirrhosis, and 80% (8/10) among patients treated for liver cancer. The SVR12 (19/25) was lowered to 76% at 12 weeks of treatment with Sofosbuvir 400 mg/ Daclatasvir 60 mg in DAA-failure patients 23/1109 (2.07%). Conclusions: SVR12 rates in non-cirrhotic and cirrhotic patients were 99.2% and 93.4%, respectively, while it was 80% in liver cancer patients after DAA treatment. As for patients with viral relapse, 76% of them were successfully retreated with second-line DAA treatment. During the DAA treatment, only 17.6% of all patients had some adverse effects related to DAA treatment, thus, DAA treatment is suitable for Mongolian patients and has less adverse effects.

Increased Risk of Age-Related Macular Degeneration with Chronic Hepatitis C Virus Infection: A Nationwide Population-Based Propensity Score-Matched Cohort Study in Taiwan.

Studies evaluating the association between age-related macular degeneration (AMD) risk and HCV infection are scant. In this population-based cohort study, 13,300 patients newly diagnosed as having HCV (HCV cohort) and 26,600 propensity score-matched patients without HCV (non-HCV cohort) were identified from the Taiwan National Health Insurance Research Database between 2000 and 2013. Furthermore, 1,983 patients with HCV who received pegylated interferon and ribavirin treatment (HCV-treated cohort) and propensity score-matched patients with HCV (matched at a ratio of 1:2) who did not receive this treatment (HCV-untreated cohort) were selected from the HCV cohort. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) associated with the risk of AMD in the HCV and non-HCV cohorts. The adjusted HR (aHR) for AMD in the HCV cohort was 1.22 (95% CI = 1.09–1.35). This significant association was observed only for nonexudative AMD (aHR = 1.22, 95% CI = 1.09–1.37). Compared with the HCV-untreated cohort, the HCV-treated cohort showed no significant association with any type of AMD (aHR = 1.07, 95% CI = 0.81–1.43). Age and sex did not modify AMD development after the exposure and treatment of chronic HCV infection. Our findings revealed that patients with chronic HCV infection had an increased risk of AMD.

Impact of direct antiviral agents (DAAs) on B-cell non-Hodgkin's lymphoma in patients with chronic hepatitis C.

The relationship between HCV infection and extrahepatic manifestations has been demonstrated by epidemiological, clinical, immunological, and pathological studies. Patients with HCV infection have an increased risk of morbidity and mortality related to these non-liver diseases. For these reasons, HCV chronic infection should be considered a systemic disease in which extrahepatic manifestations increase the severity of the disease. We performed on PubMed a literature search for the articles published up to October 2020 by using the search terms "HCV infection," "HCV syndrome," "HCV-related hematological disorders," "extrahepatic manifestation," and "HCV-related B cell non-Hodgkin's lymphoma." HCV-extrahepatic manifestations may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Over the past 5 years, treatment of chronic HCV infection in patients with hematologic malignancies has evolved rapidly and effective and safe direct-acting antivirals (DAAs) have become the standard-of-care treatment. The choice of regimens with DAAs should be individualized after thorough assessment for potential hematologic toxic effects and drug-drug interactions. Elimination of HCV from infected cancer patients confers virologic, hepatic, and oncologic benefits.

Sofosbuvir/Ledipasvir for Treatment of Chronic Hepatitis C Infection in Adult Patients with β- Thalassemia Major: A Real-Life Study.

Patients with thalassemia have a lifelong need for blood transfusion, which makes them more risky to hepatitis C virus (HCV). Iron overload and chronic HCV are considered risk factors for patients with thalassemia to develop liver insults. The aim of the present study is to investigate the safety and efficacy of sofosbuvir/ledipasvir in the treatment of chronic HCV infection in Egyptian adult patients with β- thalassemia major. A retrospective study included 53 patients with β-thalassemia major with chronic HCV treated with sofosbuvir (400 mg) and ledipasvir (90 mg) as a single pill fixed-dose combination once daily for 12 weeks. The effectiveness of the treatment was assessed by the sustained virologic response (SVR) at 12 weeks after the end of the treatment. SVR was achieved in 96.23% of patients. 47.17% of patients had minor side effects. There was a significant reduction in ALT, AST, and serum ferritin 12 weeks post-therapy. There was an insignificant change in hemoglobin level or blood transfusion requirement 12 weeks posttherapy. There was no change in iron chelators doses throughout the study period. Sofosbuvir/ledipasvir regimen seems to be safe and highly effective in the treatment of chronic HCV in patients with β-thalassemia major.

Effectiveness of directly acting oral antivirals in treatment of chronic HCV infection in children - experience from a tertiary care institute in southern India

Background: Worldwide, an estimated 71 million people are chronically infected with HCV, of which an estimated 2.1- 5.0 million are children aged ≤15 years. Children with chronic HCV infection have fewer treatment options than adults. Very few reports are available on HCV infection, treatment strategies and its outcome particularly in pediatric population. In this background, we evaluated the effectiveness and safety of Sofosbuvir/Ledipasvir in treating HCV infection in children.Methods: In this retrospective study, a total of 33 children with HCV positive status, 12 cases (children above 12 years of age) were selected for treatment. HCV-RNA quantitative assay, genotyping was carried out. Children above 12 years with HCV genotype 1 were treated with tablet ledipasvir-sofosbuvir (90/400 mg) orally once a day as morning dose for 12 weeks. Children with genotype 3 were treated with sofosbuvir 400 mg and weight based ribavirin for 24 weeks. Viral load was repeated after 12 weeks of completion of treatment with antivirals for sustained virological response (SVR 12).Results: Out of the 12 patients 11 patients had genotype 1 (5/11 had subtype-1a and 6/11 had subtype-1b) infection and only 1 patient has genotype 3 (subtype-3a). All of them attained SVR at the end of 12 weeks. The regimen was well tolerated and there were no side effects noted by the children and their caretakers. Drug compliance and the palatability of the drugs were good.Conclusions: Ledipasvir-sofosbuvir combination was highly effective at treating children with chronic HCV genotype 1 infection. The availability of an all oral, direct-acting antiviral regimen for paediatric population with chronic HCV would improve care for patients who currently have limited treatment options.

Safety and efficacy of sofosbuvir and daclatasvir in the treatment of chronic HCV infection in elderly Egyptian patients Mohamad B. Bastawy, Mostafa A. Elhawary, Mohamed G. Mohamed and Mohamad R. Rashed, Department of Hepatogastroentrology and infectious diseases, Faculty of Medicine, Al-Azhar University-Cairo

Background: Chronic Hepatitis-C virus [HCV] infection is endemic in Egypt, with the highest prevalence worldwide. There are few studies on the effectiveness and safety of direct acting antivirals in treating geriatric patients with chronic HCV. Aim of the work: This study aimed to determine the efficacy and safety of sofosbuvir and daclatasvir with or without ribavirin in treating chronic HCV infection in geriatric Egyptian patients. Patients and Methods: In this study, we analyzed the medical files of 100 patients with chronic HCV, ≥ 65 years old, naive, and eligible for HCV treatment. Patients were classified into: Group I; 50 patients without cirrhosis and Group II; 50 patients with Cirrhosis. All patients were subjected to history taking, clinical and laboratory evaluation. Electrocardiogram [ECG] and echocardiography were also conducted. Polymerase chain reaction [PCR] for HCV- ribonucleic acid [RNA] was performed and compared between groups at baseline, at the end of treatment, and at 12 weeks later. All patients underwent an abdominal ultrasound and fibrosis-4 [FIB-4] score. Group I was treated with sofosbuvir 400 mg and daclatasvir 60 mg once daily for 12 weeks, while weight-based ribavirin was added in group II. Results: Overall, 95 patients achieved sustained virological response[SVR]-12, three had failed treatment, and two had relapse. There were no significant differences in treatment success between the groups after treatment completion [HCV RNA was below the detection limit in 49 patients in group I and 48 patients in group II] and 12 weeks later [HCV RNA was below the detection limit in 48 patients in group I and 47 patients in group II], with one patient in group I and two patients in group II had failed treatment. There was also a significant decrease in alanine transaminase [ALT] and aspartate transaminase [AST] in both groups after treatment completion. Some patient symptoms like easy fatigability and dyspepsia have been improved with no significant cardiac changes after therapy.Conclusions: Sofosbuvir and daclatasvir with or without ribavirin are safe and effective in treating elderly Egyptian patients with chronic HCV infection.

The Z-Profile Study: a multicenter, retrospective cohort study toassess the real-world use and effectiveness of elbasvir/grazoprevir in Canadian adult patients with chronic hepatitis C.

Canada was the first country to approve elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic HCV infection for genotypes 1 and 4 with or without ribavirin and genotype 3 with sofosbuvir, with no recommendation for baseline resistance testing. The aim of this study was to describe the effectiveness of EBR/GZR and the profile of patients selected for treatment in a Canadian real-world setting. This multicenter retrospective study of HCV-infected patients treated with EBR/GZR took place among selected Canadian health care providers, with no exclusion criteria. Primary outcome measures included parameters associated with patient profile and sustained virologic response at 12 weeks (SVR12) and 24 weeks after treatment. A total of 408 patients were included; 244 had available SVR12 information (per-protocol population [PP]). Genotype distribution included 1a (54.7%), 1b (17.2%), 3(11.8%), 4 (10.0%), and other (6.4%). The majority (88.7%) of participants were treated for 12 weeks without ribavirin. Fifty-nine (14.5%) participants, predominantly with genotype 1a (49/59) infection, were tested for baseline resistance-associated substitutions (bRAS). SVR12 was achieved by 95.9% of the PP. In an exploratory analysis assessing potential predictors of SVR12, participants who had undergone bRAS testing (OR 0.14, 95% CI 0.03-0.64) and participants who had undergone liver transplant (OR 0.05, 95% CI 0.00-0.68) had significantly lower odds of achieving SVR12. This study supports the real-world effectiveness of EBR/GZR-including a broad range of genotypes and diverse fibrosis stages-in the absence of bRAS testing and in special populations.

Real-life experience of ledipasvir and sofosbuvir single-tablet regimen among chronic hepatitis C patients in Turkey.

Ledipasvir (LDV) and sofosbuvir (SOF) as single-tablet regimen (STR) has been approved for treatment of chronic HCV infection (CHC) for treatment-naïve or experienced cirrhotic or non-cirrhotic patients. Our aim was to analyse the effectiveness and safety of 12-24 weeks treatment of LDV/SOF (90mg/400 mg)±ribavirin in a real-life setting in Turkey. Between May-Dec 2016, 104 treatment-naïve or experienced adult patients with CHC and with or without cirrhosis (including decompensated cirrhosis) were included in this observational study. Patients were administered LDV/SOF STR± ribavirin once daily for 12 -24 weeks. SVR12 rates and effects of the baseline characteristics on SVR12 rates were assessed. Out of 104 enrolled patients (61.5% female, mean age 62.0 years); 60.6% were cirrhotic, 76.0% previously used peg-IFN, 94.2% had GT1. At the end of the treatment, 77.8% (77/99, no data for 21 patients) had undetectable HCV-RNA and 98.9% (94/95) had SVR12. In the baseline characteristics subgroups, the SVR12 rates varied between 94.4% and 100%, and none of the baseline characteristics had a significant effect on the SVR12 rates. During the study, 6 (5.8%) patients died and none of the deaths was suspected to be related to the LDV/SOF. No treatment-emergent adverse event was reported. In conclusion, LDV/SOF±ribavirin yielded very high SVR12 rates, without any safety or tolerability concern in Turkey. The effectiveness of the LDV/SOF treatment was not affected by the patient demographics or medical characteristics such as fibrosis level, cirrhosis status, previous treatment status, HCV-RNA level or HCV genotype.

Guidelines and Benefits for the Treatment of Chronic HCV Infection

Guidelines and Benefits for the Treatment of Chronic HCV Infection

Treatment of Chronic HCV Infection in Patients With Thalassemia.

Watch a video presentation of this article Watch the interview with the author Answer questions and earn CME

Serum Alpha-fetoprotein Levels and Response to Direct Antiviral Therapy in Patients with Chronic Hepatitis C: Real-world Results from 1716 Patients in Egypt.

Direct Antiretroviral Agents (DAAs), sofosbuvir-based therapies, have opened a new era in the treatment of chronic HCV infection. The aim of the study was to investigate the potential use of baseline and in serial serum, AFP levels as a predictor for response to DAAs in patients with Chronic Hepatitis C. This multicenter observational study was carried out on 1716 chronic hepatitis C virusinfected patients who received direct anti-viral drugs for 12 weeks. The primary end point was sustained virological response at 12 weeks after the end of treatment determined by quantitative PCR for HCV RNA. Serum AFP was quantitatively assessed at baseline then after 12week after stoppage of treatment (SVR12). SVR12 rate was 97.8%. Elevated serum AFP was significantly higher in non -SVR group p value (<0.001). There was a significantly marked decrease in AFP after treatment in comparison to pretreatment values. The multivariate logistic regression analysis on the resulting significant variable from the univariate analysis revealed that only AFP was significantly related to the response to direct antiviral therapy in patients with chronic hepatitis C with p <0.001, OR 1.10 (95% CI 1.07:1.12). Other sociodemographic (e.g. Age, gender, BMI, ..) or laboratory factors (Hb, ANC, WBCs, …) did not show any significant association with the patients' response to treatment. Serum AFP levels were a predictor for response in patients with chronic HCV with the administration of direct antiviral drugs.

Efficacy of Sofosbuvir plus Daclatasvir in Treatment of Chronic HCV Infection in Egyptian Patients: A Prospective Cohort Study

Background and study aim: Chronic hepatitis C virus infection is a massive health challenge in Egypt. New DAAs in the past few years have proven to be extremely effective in treatment of HCV infection. The aim of this study was to evaluate the efficacy of a sofosbuvir-based treatment protocol composed of sofosbuvir and daclatasvir with or without the addition of ribavirin in Egyptian patients infected with HCV genotype 4 in Sharkia governorate. Patients and Methods: One hundred patients were included in the study. Patients were divided into three groups, group I: 48 treatment-naive non-cirrhotic patients who were assigned to receive dual therapy (Daclatasvir+Sofosbuvir) for a duration of 12 weeks, group II: 32 treatment-naive cirrhotic patients who were assigned to receive triple therapy (Daclatasvir + Sofosbuvir + Ribavirin) for a duration of 12 weeks, and group III: A control group composed of 20 chronic HCV patients, not receiving antiviral therapy. Patients were followed up thoroughly by clinical and laboratory evaluation monthly throughout treatment and for 3 months after the end of treatment (EOT). In addition, the virological response for each patient was recorded. Results: No statistically significant difference was found between both groups that received treatment regarding virological response, since 100% of patients achieved SVR12 rates in both groups. Conclusion: The combination of Daclatasvir plus Sofosbuvir with or without the addition of ribavirin for a duration of 12 weeks has proven to possess high efficacy in the treatment of cirrhotic and non-cirrhotic naive Egyptian patients with chronic infection with HCV genotype4 in Sharkia governorate.

SOFOSBUVIR: TREATMENT OF CHRONIC HEPATITIS C AND THE MAIN TRENDS IN PATENT PROTECTION

The purpose of the study was to analyze and systematize the literature data on the benefit/risk ratio of sofosbuvir administration in the treatment of patients with chronic hepatitis C and the main trends in its patent protection. Studies were conducted using databases on the Internet: Ukrainian patent office, the European patent office, the US patent office, the Food and drug administration, European Medicines Agency (EMEA), State enterprise “The State Expert Center” of the Ministry of Health of Ukraine. It has used retrospective, logical, systematic and analytical methods. Data from clinical studies abroad and meta-analyses indicate that sofosbuvir is one of the most promising drugs for the treatment of chronic HCV infection. Its indisputable advantages are that this drug can be used with different genotypes of the virus, decompensated liver function, it is well tolerated. Sofosbuvir has an improved safety profile and a low probability of viral resistance. The high cost of sofosbuvir is due to the powerful patent protection. As mechanisms for working with patent barriers, it is recommended to use the flexible mechanisms of the TRIPS Agreement: the grant of compulsory licenses, the implementation of parallel imports, the tightening of the criteria for patentability (prohibition of patenting new forms that do not improve therapeutic efficacy).