Treatment Of Chronic Hepatitis C Virus Research Articles

High efficacy and safety of direct-acting antivirals for the treatment of chronic hepatitis C: A cohort study conducted in Vietnam.

Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha-fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well-tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies.

Generic sofosbuvir and daclatasvir for treatment of hepatitis C virus infection in patients with sickle cell disease

Background and purpose of the studySickle cell disease (SCD) patients are at a high risk of chronic liver disease (CLD) due to chronic viral hepatitis infection such as hepatitis C virus (HCV) infection, iron overload, and sickle cell hepatopathy. Nowadays, several oral direct-acting antiviral drugs (DAAs) have been developed and approved by the FDA for hepatitis C treatment. However, the safety and efficacy of DAAs in SCD patients remain insufficiently explored.Purpose of the studyTo evaluate the efficacy and safety of administration of generic sofosbuvir (SOF) and daclatasvir (DCV) for 12 weeks in SCD patients infected with HCV.MethodsA retrospective study included 38 SCD patients infected with HCV treated with generic SOF (400 mg) and DCV (60 mg) for 12 weeks without ribavirin. The effectiveness of the HCV treatment was assessed by the sustained virologic response (SVR) at 24 weeks after the end of the treatment (SVR24).ResultsThe SVR24 rate was 100% (38/38).There were insignificant alterations in hemoglobin and total bilirubin levels during HCV treatment or at end of treatment (EOT). The number of anemic patients who needed blood transfusion two weeks before HCV treatment, at week 4 of treatment, and at EOT was 11 (28.9%), 3 (8%), and 1 (3%) respectively. Moreover, the reductions in serum transaminase levels from baseline were statistically significant compared to the EOT.ConclusionGeneric SOF and DCV regimens appear to be safe and effective in the treatment of chronic HCV in patients with SCD.

Identification and characterization of Sofosbuvir-resistant mutations of hepatitis C virus genotype 3a replicon.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. Among its 8 genotypes (GT), GT3 has a relatively lower sustained virological response to highly effective direct-acting antiviral agents (DAA). Sofosbuvir (SOF), an anti-NS5B polymerase inhibitor, is a core component of many anti-HCV DAA cocktail regimens, and its resistant mutations are rare in clinics because these mutations usually severely impair the NS5B polymerase activity, including a mutation S282T in NS5B, the most frequently reported SOF-resistant mutation. In this study, we selected SOF-resistant variants of a previously developed GT3 subgenomic replicon (PR87A7). Two mutations were identified in the viral genome of SOF-resistant PR87A7 variants, Q606R in nontargeted NS3 and S282T in targeted N5SB. We demonstrated that Q606R could rescue the replication defect of S282T in PR87A7, and the resulting double mutant confers the SOF resistance. Finally, we showed that NS3-606R could not compensate for the replication defect of S282T in other GTs. In conclusion, we identified a novel GT3-specific combination of two mutations that confers SOF resistance. Our result calls for attention to potential mutations that may arise in nontargeted viral proteins during the SOF-based DAA treatment of chronic HCV.

Identification of the Genotypes Circulating in the Ecuadorian Population Infected with the Hepatitis C Virus (HCV).

The hepatitis C virus (HCV) is responsible for 1.5 million new infections, and around 290 thousand deaths worldwide. 15 to 30% of the patients that go into a chronic phase of the disease will develop cirrhosis or hepatocellular carcinoma within 20 years and is the leading etiology for liver transplantation. HCV genetic characteristics display a remarkable genetic diversity, which divides HCV into 8 genotypes and 67 subgenotypes; the treatment and probability of chronic HCV depend on these genotypes and subgenotypes. In Ecuador, there is no available information regarding HCV genotypes and subgenotypes; therefore, this study aims to provide an overview of the main genotypes circulating in Ecuador. In a cross-sectional and descriptive study using the Ecuadorian Ministry of Health (MSP) registry of patients already diagnosed with Hepatitis C (HCV) between 2017 and 2019. From 51 patients identified by health ministry, blood samples from a total of 15 subjects (named HCV1 to HCV15) were collected using an appropriate venipuncture technique. Pandemic-related circumstances avoid reaching all patients identified by health ministry. After the amplification of 11 samples from patients living in the Ecuadorian territory, the genotypes of HCV obtained were distributed as follows: 6 samples corresponding to subgenotype 2b (54.5%), 2 samples corresponding to subgenotype 1a (18.2%), 2 samples corresponding to subgenotype 4d (18.2%) and 1 corresponding to sample 1b (9.1%). These results represent the first epidemiological approach to genotype distribution in Ecuador, and it contributes to better management of patients. We emphasize the importance of the development of better strategies from the Healthcare Ministry of Ecuador (MSP) for the identification, treatment and tracking of HCV patients.

Trends in hepatitis C virus coinfection and its cascade of care among adults living with HIV in Asia between 2010 and 2020.

Chronic hepatitis C virus (HCV) infection contributes to substantial morbidity and mortality among adults living with HIV. Cascades of HCV care support monitoring of program performance, but data from Asia are limited. We assessed regional HCV coinfection and cascade outcomes among adults living with HIV in care from 2010-2020. Patients ≥18 years old with confirmed HIV infection on antiretroviral therapy (ART) at 11 clinical sites in Cambodia, China, India, Indonesia, South Korea, Thailand and Vietnam were included. HCV- and HIV-related treatment and laboratory data were collected from those with a positive HCV antibody (anti-HCV) test after January 2010. An HCV cascade was evaluated, including proportions positive for anti-HCV, tested for HCV RNA or HCV core antigen (HCVcAg), initiated on HCV treatment, and achieved sustained virologic response (SVR). Factors associated with screening uptake, treatment initiation, and treatment response were analyzed using Fine and Gray's competing risk regression model. Of 24,421 patients, 9169 (38%) had an anti-HCV test, and 971 (11%) had a positive result. The proportion with positive anti-HCV was 12.1% in 2010-2014, 3.9% in 2015-2017, and 3.8% in 2018-2020. From 2010 to 2014, 34% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 66% initiated HCV treatment, and 83% achieved SVR. From 2015 to 2017, 69% with positive anti-HCV had subsequent HCV RNA or HCVcAg testing, 59% initiated HCV treatment, and 88% achieved SVR. From 2018 to 2020, 80% had subsequent HCV RNA or HCVcAg testing, 61% initiated HCV treatment, and 96% achieved SVR. Having chronic HCV in later calendar years and in high-income countries were associated with increased screening, treatment initiation or achieving SVR. Older age, injecting drug use HIV exposure, lower CD4 and higher HIV RNA were associated with reduced HCV screening or treatment initiation. Our analysis identified persistent gaps in the HCV cascade of care, highlighting the need for focused efforts to strengthen chronic HCV screening, treatment initiation, and monitoring among adult PLHIV in the Asia region.

Current Therapy of Chronic Viral Hepatitis B, C and D.

The majority of chronic viral hepatitis cases are induced via infection with the hepatitis B virus (HBV), hepatitis C virus (HCV), or hepatitis D virus (HDV). These patients are at increased risk for progressive liver disease leading to cirrhosis as well as hepatocellular carcinoma (HCC). HBV infection is well controlled by the currently available nucleosides as well as nucleotides, and the development of cirrhosis can be prevented. Additionally, it has been shown that HBV-induced liver fibrosis can regress during successful antiviral treatment; however, a "functional cure", i.e., loss of HBsAg, is a rare event when these drugs are used. Therefore, novel therapeutic strategies are aiming at the selective suppression of HBsAg levels in combination with immunostimulation. The development of directly acting antivirals (DAAs) has revolutionized HCV therapy, as almost all patients can be cured via this treatment. Additionally, DAA therapy has few, if any, side effects, and is generally well tolerated by patients. HDV remains the most challenging type of chronic viral hepatitis. Although novel therapeutic options have recently been approved, response rates are still less favorable compared to HBV and HCV. This review discusses current and future options for the treatment of chronic HBV, HCV, and HDV infection.

Effectiveness of Differentiated Hepatotrophic Therapy in Complex Management of Patients with Comorbidity of Chronic Pancreatitis and Chronic Viral Hepatitis С

An important problem of the combined course of chronic pancreatitis (CP) and chronic hepatitis C virus (HCV) is the study of the effects of chronic HCV, even after the treatment, in particular for the condition of the pancreas and liver in patients with CP. Often hepatotrophic therapy is used for this purpose, which should be differentiated depending on the needs of patients with comorbidity of CP and chronic HCV. The objective: to analyze the functional and structural condition of the pancreas and liver in patients with CP after the chronic HCV treatment by the proposed complex treatment with additional inclusion of hepatotrophic drugs. Materials and methods. 80 patients with a combined course of CP and chronic HCV were examined. According to the methods of treatment the patients were divided into three groups. The 1st group included 20 patients with CP and chronic HCV, who received a common complex for treatment (CCT) by protocol for 3 months. In the 2d group 25 patients with CP and chronic HCV received CCT with additional inclusion of hepatotrophic agent for 3 months. The 3d group included 35 patients with CP and chronic HCV with CAGE≥2.0, who took CTC with additional inclusion of hepatotrophic agent for 3 months and metadoxine for 3 months. Results. The more significant level of efficiency of therapeutic complex with the additional inclusion of hepatotrophic agent was determined when metadoxine was prescribed. It was found that the content of fecal α-elastase increased by 19.6 %, 37.5 % and 66.9 %, glucose level decreased by 13.4 %, 11.0 % and 28.4 %, glyconized hemoglobin – by 12.3 %, 22.1 % and 25.8 %, HOMA index – by 16.3 %, 21.9 % and 56.0 %, coprogram score – by 12.8 %, 18.3 % and 88.7 %, the total index of the pancreas structure – by 7.2 %, 15.1 % and 85.7 %, and the total indicator of liver structure – by 11.7 %, 17.5 % and 44.7 %, respectively in groups (p<0.05). It was established that the inclusion of the hepatotrophic medicine in the standard therapy of CP with chronic HCV improved the results of treatment for the restoration of the functional and structural condition of the pancreas. Conclusions. The additional prescription of the hepatotrophic agents combination significantly increased the effectiveness of treatment according to the dynamics of the functional capacity of pancreas and restoration of its structure (p<0.05). It was confirmed that a complex medical program with additional use of polysubstrate hepatoprotector exceeded the efficiency of the protocol treatment for the structural condition of the liver by 36.0 %, and with a combination of hepatotrophic agents – by 51.9 %; regarding the pancreas condition – by 22.3 % and 38.3 %, respectively (p<0.05). The combined use of hepatotrophic agents was also more effective than monotherapy with one drug.

Mathematical modeling of HIV-HCV co-infection model: Impact of parameters on reproduction number.

Background:Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) are both classified as blood-borne viruses since they are transmitted through contact with contaminated blood. Approximately 1.3 million of the 2.75 million global HIV/HCV carriers are people who inject drugs (PWID). HIV co-infection has a harmful effect on the progression of HCV, resulting in greater rates of HCV persistence after acute infection, higher viral levels, and accelerated progression of liver fibrosis and end-stage liver disease. In this study, we developed and investigated a mathematical model for the dynamical behavior of HIV/AIDS and HCV co-infection, which includes therapy for both diseases, vertical transmission in HIV cases, unawareness and awareness of HIV infection, inefficient HIV treatment follow-up, and efficient condom use. Methods:Positivity and boundedness of the model under investigation were established using well-known theorems. The equilibria were demonstrated by bringing all differential equations to zero. The associative reproduction numbers for mono-infected and dual-infected models were calculated using the next-generation matrix approach. The local and global stabilities of the models were validated using the linearization and comparison theorem and the negative criterion techniques of bendixson and dulac, respectively. Results: The growing prevalence of HIV treatment dropout in each compartment of the HIV model led to a reduction in HIV on treatment compartments while other compartments exhibited an increase in populations . In dually infected patients, treating HCV first reduces co-infection reproduction number R ech , which reduces liver cancer risk. Conclusions:From the model's results, we infer various steps (such as: campaigns to warn individuals about the consequences of having multiple sexual partners; distributing more condoms to individuals; continuing treatment for chronic HCV and AIDS) that policymakers could take to reduce the number of mono-infected and co-infected individuals.

National Hepatitis C estimates: Incidence, prevalence, undiagnosed proportion and treatment, Canada, 2019.

Estimates of the number of hepatitis C virus (HCV) infections are important for monitoring efforts aimed at preventing disease transmission, especially following the introduction of a highly effective treatment. This report provides updated estimates of HCV incidence, prevalence, undiagnosed proportion and treatment in Canada. A combination of back calculation modelling and a modified version of the workbook method were used to estimate the incidence and prevalence of anti-HCV positive persons, the prevalence of chronic HCV infection and the undiagnosed proportion. The number of people treated for chronic HCV was estimated using administrative pharmaceutical data. An estimated 9,470 new infections occurred in 2019, corresponding to an incidence rate of 25 per 100,000 population, a 7.7% decrease since 2015. The estimated prevalence of anti-HCV antibodies in the Canadian population was 1.03% (plausible range: 0.83%-1.38%), and the estimated prevalence of chronic HCV was 0.54% (plausible range: 0.40%-0.79%). The overall proportion of anti-HCV positive persons who were undiagnosed was estimated at 24% of all infections, with individuals born between 1945 and 1975 being the priority population the most likely to be undiagnosed. An estimated 74,500 people with chronic HCV have been treated since the introduction of direct-acting antivirals in 2014. Estimates of HCV incidence and prevalence are key metrics to guide interventions and resource allocation. While our estimates show that HCV incidence has decreased in Canada in recent years and treatment of chronic HCV has continued to increase, ongoing efforts are required to reduce the burden of HCV in Canada.

Impact of proton pump inhibitors on sustained virologic response in veterans treated with sofosbuvir/velpatasvir for chronic hepatitis C virus: A retrospective cohort study.

The objective of this study was to determine the clinical relationship between proton pump inhibitor (PPI) use and sustained virologic response (SVR) in patients treated with sofosbuvir/velpatasvir (SOF/VEL) for chronic hepatitis C virus (HCV) infection. This was a multicenter retrospective cohort study. Data was collected on patients from 128 Veterans Affairs Medical Centers throughout the United States. This study included veterans aged 18-89 years with viremic HCV who received a full course of SOF/VEL treatment from June 2016 - July 2017. Sustained viral response was compared in patients taking SOF/VEL with or without concurrent PPI prescriptions. Analysis of the primary outcome was completed utilizing logistic regression. The relationship between SVR and PPI use was adjusted for African-American race, presence of cirrhosis, prior treatment, BMI greater than 30 kg/m2, and HCV genotype. The final analysis included 4,008 veterans, 830 with concomitant PPI use and 3,178 without PPI use. After adjustment for other variables in the logistic model, there was no statistically significant association between PPI use and lower SVR (odds ratio 0.67; 95%CI: 0.42, 1.06; p=0.087). Concomitant PPI treatment adjusted for other variables did not significantly impact success or failure of SOF/VEL treatment of chronic HCV. Despite the lack of significant association identified in this study, in efforts to provide the best care possible, it remains prudent to proceed with caution in patients desiring to use PPI therapy while receiving SOF/VEL, and ensure prescribing instructions are closely followed in regard to concomitant PPI use, especially in patients with other risk factors for decreased SVR.

Quality improvement to evaluate and provide treatment for chronic hepatitis C postpartum

BackgroundChronic hepatitis C virus (HCV) infections are increasing among reproductive age individuals. Direct acting antivirals (DAAs) can cure HCV, but the use of DAAs is not currently recommended during pregnancy and breastfeeding. Individuals with HCV commonly have inadequate prenatal and postnatal care. ObjectivesThe purpose of our study was to demonstrate the success of a quality improvement program to increase evaluation during pregnancy and ensuring access to DAA treatment medication during the postpartum period for individuals with chronic HCV to achieve cure 12 weeks after completing therapy. The primary outcome was documented HCV cure rate compared among individuals who received immediate treatment with DAA after delivery or after weaning or a traditional approach of referral to an infectious diseases specialist or hepatologist. The secondary outcome was the proportion of infants exposed to HCV evaluated. MethodsAn interdisciplinary team developed a program to increase evaluation and HCV treatment for postpartum individuals. Individuals who received prenatal care from March 2017 to May 2021 were eligible. Individuals with chronic HCV had a laboratory evaluation before delivery, and appropriate DAAs were selected for postpartum treatment. The health system specialty pharmacy dispensed DAA prescriptions immediately after delivery to those who were not breastfeeding. Individuals who did breastfeed had the option to begin treatment after weaning. Cure was defined as a sustained viral response or undetectable HCV RNA collected 12 weeks after completing DAA treatment. ResultsWe demonstrate the success of an interdisciplinary team to ensure access to therapy for the treatment of postpartum chronic HCV. Only 3 infants (25%) with mothers referred were evaluated at our institution compared with 44% of infants (n = 10) whose mothers were treated after delivery. ConclusionAn interdisciplinary team for HCV treatment improves access to treatment therapy with DAAs leading to the cure of chronic HCV after delivery.

Efficacy and safety of sofosbuvir plus daclatasvir with or without ribavirin in treatment of Egyptian patients infected with chronic HCV (Single Centre Study)

Abstract Background and aim As indicated by the World Health Organization (WHO), Egypt is positioned as the country with the world’s highest prevalence of Hepatitis C virus (HCV). The current study was designed to describe the efficacy and safety of Sofosbuvir plus Daclatasvir with or without Ribavirin in treatment of chronic HCV in a cohort of Egyptian patients who were referred to the viral hepatitis unit in El -Fayoum general hospital. Methods This is a prospective descriptive cross sectional study that describes the effect of 12 weeks of daily Sofosbuvir (SOF) 400 mg plus Daclatasvir (DCV) 60 mg with or without ribavirin (RBV) with dose adjustment if indicated. It included 200 patients that fulfilled the inclusion and exclusion criteria and treated in El -Fayoum general hospital, El-Fayoum, Egypt. Results In the current study, concerning viral response, SVR12 rate was achieved by 92.5% in the overall patients (185/200); by 98% (98/100) in group I, and by 87% (87/100) in group II. Concerning safety and tolerability, The main adverse effects recorded during and after 12 weeks of treatments were fatigue (46%), (66%); headache (24%), (40%); gastrointestinal upset (15%), (43%); and nausea (10%), (15%) in group 1 and group 2, respectively. Only one female patient in group II developed HCC. All patients completed treatment till the end of course. Conclusion The current study suggested that treatment of SOF plus DCV with/without RBV for chronic HCV patients in Egypt was generally safe, well tolerated, and of high efficacy, reflecting the antiviral potency and high resistance barrier of the combination regimen.

Direct-Acting Antivirals in the Treatment of Hepatitis C Virus (HCV)/Human Immunodeficiency Virus (HIV) Co-infected Patients: Real-Life Experience From Nepal.

BackgroundDirect-acting antivirals (DAA) have revolutionized the treatment of chronic hepatitis C patients. However, the real-life data regarding its use in a human immunodeficiency virus (HIV) co-infection from a developing country is lacking. We aimed to see the efficacy of DAA in hepatitis C virus (HCV)/HIV co-infected populations.MethodsIn this prospective, observational, intention-to-treat study from Nepal, treatment-naïve patients undergoing treatment for chronic HCV in HIV co-infected individuals with DAA were studied. Patients on nevirapine were switched to efavirenz or atazanavir. Patients received sofosbuvir/ledipasvir or sofosbuvir/daclatasvir with or without ribavirine. Sustained virological response (SVR) at week 12, adverse events, and treatment compliance were evaluated. Treatment efficacy was compared between cirrhotic and non-cirrhotic patients.ResultsOf 218 patients presenting with an anti-HCV report, 181 (83%) had detectable HCV RNA. Eighty-five (85; 47%) patients were having ART at presentation. Three patients could not complete treatment due to gall stone pancreatitis and 82 completed treatment. Twenty-nine (29; 35%) were cirrhotic at presentation. Fifty-one (51; 62%) patients were genotype 3, 27 (33%) were genotype 1, three (4%) were mixed 1a/3, and one (1%) was 6. Seventy-four (74; 90%) had SVR12. Non-cirrhotics had 96% SVR compared to 79% in cirrhotics. SVR in genotype 3 was 88% while it was 93% in genotype 1.ConclusionsReal-life experience showed that the DAAs are equally effective in HCV HIV co-infected patients. In non-cirrhotic patients, the result is comparable to mono-infected patients. Genotype 3 co-infected are also difficult-to-treat patients. DAA treatment is well-tolerated in HCV/HIV co-infected patients, and there was no dropout during treatment.

Hepatitis C core antigen: a simple predictive marker for treatment response to the new direct-acting antiviral drugs in chronic HCV Egyptian patients

BackgroundSuccessful eradication of hepatitis C virus (HCV) has great impact on the prognosis of HCV-related complications and the associated mortality. The development of the new direct-acting antiviral drugs (DAAs) has revolutionized the treatment of HCV infection. HCV core antigen (HCVcAg) is a recently developed marker that displayed a good correlation with HCV RNA assays. Our main objectives were to correlate between serum levels of HCVcAg and HCV RNA loads in chronic HCV patients as well as to explore the potential value of HCVcAg assay in predicting treatment response to the new DAAs. The study enrolled a total of 280 chronic HCV-infected patients scheduled to start the new regimen for treatment of chronic HCV by all-oral, interferon-free DAAs. According to the viral load, the studied individuals were arranged into three groups corresponding to mild, moderate, and sever viremia. Serum level of HCVcAg was determined by ELISA technique and HCV RNA viral loads were quantified using the real-time PCR system. The assays were performed three times for all participants: prior to initiation of treatment, at the end of treatment (week 12), and 3 months post-treatment cessation (week 24).ResultsA statistically significant difference between HCV RNA and HCVcAg baseline levels among different viremia groups was detected (P < 0.001). There was a significant positive correlation between HCV RNA and HCVcAg baseline values among all the studied cases (P < 0.05) with a correlation coefficient of 0.752, 0.976, and 1.00 respectively for mild, moderate, and severe viremia groups. 92.9% (260/280) of the studied patients achieved sustained virologic response, 3.6% (10/280) were non-responders, and 3.6% (10/280) had recurrent viremia/relapse as regards RT-PCR results.ConclusionHCVcAg is a promising alternative to HCV RNA assay. The ELISAs for HCVcAg proved excellent correlations with HCV RNA levels. Moreover, HCVcAg can be introduced as a simple and highly specific tool for monitoring the new DAA regimens particularly in low-resource settings.

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 Sofosbuvir Combined with Direct Acting Antivirals in Hepatitis C Patients in a Tertiary Teaching Hospital in Qatar: A Retrospective Observational Study

Background: Hepatitis C virus (HCV) infection is associated with significant morbidity and mortality. The effectiveness of sofosbuvir, as a new direct-acting antiviral (DAA) for chronic HCV infection, needs to be assessed and evaluated among patients with or without cirrhosis with all HCV genotypes.&#x0D; Aims: This study was conducted to determine the effectiveness of chronic HCV treatment as part of a combination therapy for all HCV genotypes in patients with or without cirrhosis.&#x0D; Study Design: A retrospective observational study.&#x0D; Methodology: All patients who received sofosbuvir treatment from the Pharmacy Department of Hamad General Hospital during a 12-month period (between 2014 and 2015) were included. Patients were observed up to 12 weeks after treatment course completion. Data were analyzed descriptively and compared using a paired t-test (alpha=0.05).&#x0D; Results: A total of 95 patients received sofosbuvir. All of these patients received sofosbuvir in combination with other antiviral medications. All HCV genotypes were included; 1a and 4 were the most dominant genotypes (37% and 30.5%, respectively). Half of the patients were treatment naïve. All patients achieved undetectable virus ribonucleic acid (RNA) starting from week 4 of the treatment. A sustained virological response at 12 weeks (SVR12) after completion of the treatment period was maintained in 95% of patients. Relapse was mostly observed in patients with genotype 1a (40%); no patients with HCV genotype 3 exhibited relapse.&#x0D; Conclusion: The SVR12 after sofosbuvir treatment was maintained in most patients, regardless of genotype, HCV complications HCV or co-administered drugs.

S1007 Epidemiology of Extrahepatic Manifestations of Chronic Hepatitis C Infection: A National, Population-Based Study

INTRODUCTION: Although primarily an infection of the liver, chronic hepatitis C virus (HCV) infection has been associated with numerous extrahepatic manifestations (EHM). These include autoimmune, lymphoproliferative, dermatologic and renal disorders. Although a direct causal link has not been well established, experimental studies have shown that HCV can disrupt the body’s immune system and induce autoimmunity. Despite being a major cause of morbidity and mortality, large scale studies describing the epidemiologic characteristics of these EHM are limited. METHODS: We evaluated the prevalence of EHM among patients with chronic HCV infection using a large commercial database called Explorys, which is an aggregate of electronic health data from 26 US healthcare systems. We identified patients with chronic HCV infection between June 2015 and June 2020, based on Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). Within this cohort, we investigated the prevalence of several well documented EHM associated with chronic HCV (Table 1) and compared it with the control group (active patients without chronic HCV infection). RESULTS: Of the 39,212,680 individuals active in the database, we identified a total of 181,450 individuals with chronic HCV infection. Prevalence of chronic HCV infection was 0.46%, and was higher among African Americans in comparison to Caucasians (prevalence ratio (PR): 1.78, 95 CI 1.76–1.81), and higher among men than women (PR: 1.70; 95 CI 1.68–1.72). Compared to our control, patients with chronic HCV had significantly higher prevalence of various EHM including dermatologic, rheumatoid, hematologic, and autoimmune diseases that were described in our study (Table 1). Notably, relative to the patients without HCV, the prevalence ratio of cryoglobulinemia was the highest compared to other EHM (PR: 102.5; 95 CI 93.1–112.9). Interestingly, we also found no significant difference in prevalence of Hashimoto thyroiditis between the chronic HCV cohort and control group (OR: 0.953; 95 CI 0.88–1.03 P < 0.3). CONCLUSION: This is one of the largest studies to date describing the epidemiological characteristics of EHM among patients with chronic HCV infection. EHM are often the initial presenting complaint among patients with undiagnosed chronic HCV infection. Hence, understanding its prevalence is an integral factor in appropriate screening and treatment of chronic HCV infections.Table 1.: Prevalence ratio of EHM among patients with chronic HCV infection (compared to patients without chronic HCV infection)

Pre-existing resistance associated polymorphisms to NS3 protease inhibitors in treatment naïve HCV positive Pakistani patients.

Chronic Hepatitis C Virus (HCV) infection is still a major health issue especially in endemic areas where fewer direct-acting virals (DAAs) are treatment options. Some HCV variants are associated with resistance and it reduces DAAs success where pre-existing variants prevail. In this study, we investigated resistance-associated polymorphisms (RAPs) in the HCV NS3 region from DAAs naïve Pakistani patients. 277 chronic HCV treatment naïve patients infected with genotype 1a, 3a and 3b were selected from various clinical centers in the capital city of Khyber Pakhtunkhwa province Pakistan. All the patients were included in this study after taking informed consent. HCV NS3 region was amplified and Sanger sequencing was performed to analyze RAPs to NS3 protease inhibitors. Of the total 29.24% (81/277) patients had detected with known RAPs viz V36A/G/L, T54S, V55A/D/I, Q80K/R, S122G/T/R, R155K/T/I, V158I, D168T/Q, and I170V. Among HCV-1a subjects overall RAPs found were 26.09% (12/46) and most prevalent substitutions were V36A/G (10.87%, 5/46) and R155K/T/I (8.70%, 4/46). Of the total HCV-3a infected patients, 30.95% were observed with RAPS. Ammon these, the most frequent substitutions were Q80R (13.69%, 23/168) followed by V36L (18.33%, 14/168) and V55I (5.95%, 10/168). Among HCV-3b patients, 26.98% were found with RAPs and S122R and Q80R were the dominant variants detected in 17.46 (11/63) and 12.70% (8/63) patients respectively. All these substitutions were associated with Boceprevir, Simeprevir, Telaprevir, and Paritaprevir. Single substitution in one sequence was found in 18.77% (52/277) and multiple in 10.46% (29/277). More than one RAP was frequent in HCV-3a sequences. Natural RAPs are common in chronic HCV patients infected with genotype 1a, 3a and 3b, the most prevalent subtypes in Pakistan. High prevalence of HCV NS3 RAPs suggested a large scale study of the NS3 gene before the introduction of NS3 protease inhibitors in Pakistan.

An unwanted side effect: Giant hepatocellular carcinoma development after ledipasvir/sofosbuvir therapy in a chronic hepatitis C virus-induced cirrhotic patient

Hepatocellular carcinoma (HCC) is the fifth common cancer and the second cause of cancer-related death worldwide. Hepatitis C virus (HCV) is a common cause of chronic hepatitis, liver cirrhosis, and HCC. Recently, some new drugs have been developed named direct-acting antivirals (DAAs) for chronic HCV treatment. Direct-acting antivirals provide sustained viral response and total cure in over 80% of chronic hepatitis C patients. In this article, we present a patient with HCV genotype 1b-induced cirrhosis with giant HCC development after ledipasvir/sofosbuvir combination therapy. Although chronic hepatitis C infection can be cured with the combination of new generation DAAs, HCC pathogenesis and development risk in cirrhotic cases are still unclear. Thus, cirrhotic patients treated with DAAs should be followed-up at close intervals after treatment.

Study of the Effectiveness of Ledipasvir/Sofosbuvir Treatment Regimen in Patients with Chronic Hepatitis C Virus (HCV) Infection

Abstract Background: Treatment of Hepatitis C Virus (HCV) infection had significantly changed during the last few years. The combination of Sofosbuvir and Ledipasvir (SOF/LDV) has been shown to treat high proportions of patients with HCV. Aim of Study: The aim of the work was to assess the efficacy and risk factors for failure of SOF/LDV in Egyptian patients with HCV infection. Patients and Methods: In this prospective study, 138 patients who were HCV antibody positive and HCV RNA positive by Polymerase Chain Reaction (PCR), aged between 18 and 75 years, were enrolled. The patients assessed demo-graphically, and by laboratory and ultrasound. The patients received daily Sofosbuvir 400mg plus Ledipasvir 90mg for 12 weeks, the primary end point was a sustained virological response at 12 weeks (SVR12) after the end of treatment, determined by quantitative PCR for HCV RNA. The patients were classified into two groups according to SVR12: Respond-ers included 133 patients who had undetectable level of HCV RNA and non-responders included 5 patients who had detect-able level of HCV RNA. Results: The overall SVR12 was 96.4%. The response of cirrhotic vs. non-cirrhotic patients was (80% vs. 98.4) with statistically significant p-value (p<0.05) with specificity 90% and sensitivity 60% (odds ratio=15.125, 95% confidence interval 2.29-99.6, p<0.05), and the response of naive vs. experienced patients was (97.6% vs. 83.3%) with statistically significant p-value (p<0.05) with specificity 92.5% and sensitivity 40% (odds ratio=8.2, 95% confidence interval 1.22-54.9, p<0.05). Conclusion: Sofosbuvir/Ledipasvir combination for 12 weeks was very effective for chronic HCV treatment, cirrhosis and treatment-experienced patients were associated with decreased likelihood of SVR.