scholarly journals Safety and efficacy of direct-acting antiviral drugs in the treatment of chronic hepatitis C virus infection in patients with thalassemia: a prospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elsayed Ghoneem ◽  
Ahmed Saleh ◽  
Shahira Aly El-Etreby ◽  
Metwaly Ibrahim Mortada ◽  
Mayada A. Ghannam ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Virologic Response ◽  
Direct Acting Antiviral ◽  
Significant Difference ◽  
Before And After ◽  
Chronic Hcv ◽  
Direct Acting ◽  
A Prospective Study

Abstract Background Hepatitis C virus (HCV) infection is a major cause of liver-related morbidity and mortality among thalassemic patients. Direct-acting antiviral agents (DAAs) are highly effective and well-tolerated by chronic HCV patients. Results The mean age of our patients was 29 years. Sustained virologic response (SVR) at 12 and 24 weeks was achieved in all patients (100%). The most common side effects were fatigue (18%), anemia (13.63%), and headache (4.5%). There was no statistically significant difference in the hemoglobin level before and after treatment (p = 0.48). There was a significant improvement in serum bilirubin and mean ALT levels after treatment compared to baseline data (p < 0.0005 each). Conclusions DAAs, namely, sofosbuvir plus daclatasvir or sofosbuvir plus ledipasvir, are effective and well-tolerated regimens in thalassemic patients with chronic HCV.

scholarly journals Direct-acting antiviral therapy improves kidney survival in hepatitis C virus–associated cryoglobulinaemia: the RENALCRYOGLOBULINEMIC study

2020 ◽  
Author(s):  
Ana Pérez de José ◽  
Javier Carbayo ◽  
Anna Pocurull ◽  
Teresa Bada-Bosch ◽  
Clara Maria Cases Corona ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Treatment ◽  
Antiviral Agents ◽  
Direct Acting Antiviral ◽  
Primary Endpoints ◽  
Kidney Involvement ◽  
Before And After ◽  
Mixed Cryoglobulinaemia ◽  
Direct Acting

Abstract Background Direct-acting antiviral agents (DAAs) have shown high rates of sustained virological response in chronic hepatitis C virus (HCV) infection. However, the influence of DAAs on the course of kidney involvement in HCV-associated mixed cryoglobulinaemia (HCV-MC) has been little studied. The aim of this study was to analyse the effects of antiviral treatment on kidney prognosis and evolution in patients diagnosed with HCV-MC. Methods The RENALCRYOGLOBULINEMIC study is an observational multicentre cohort study of 139 patients with HCV-MC from 14 Spanish centres. Clinical and laboratory parameters were measured before and after antiviral treatment. Primary endpoints were kidney survival and mortality after HCV-MC diagnosis. Secondary endpoints were clinical, immunological and virological responses after antiviral treatment. Results Patients were divided into three groups based on the treatment received: treatment with DAAs (n = 100) treatment with interferon (IFN) and ribavirin (RBV) (n = 24) and no treatment (n = 15). Patients were followed up for a median duration of 138 months (interquartile range 70–251. DAA treatment reduced overall mortality {hazard ratio [HR] 0.12 [95% confidence interval (CI) 0.04–0.40]; P &lt; 0.001} and improved kidney survival [HR 0.10 ( 95% CI 0.04–0.33); P &lt; 0.001]. Conclusions Results from the RENALCRYOGLOBULINEMIC study indicated that DAA treatment in patients with HCV-MC improves kidney survival and reduces mortality.

scholarly journals Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Fabián Aldunate ◽  
Natalia Echeverría ◽  
Daniela Chiodi ◽  
Pablo López ◽  
Adriana Sánchez-Cicerón ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
South American ◽  
Genotype 1 ◽  
Direct Acting Antiviral ◽  
Naturally Occurring ◽  
Before And After ◽  
Treatment Naïve ◽  
Direct Acting

Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.

Detection of Occult Hepatitis C Virus Infection in Patients Who Achieved a Sustained Virologic Response to Direct-Acting Antiviral Agents

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Mohamed Yousef ◽  
Maha Mohsen Mohamed Kamal El Din ◽  
Tari Magdy Aziz George ◽  
Amr Adel Elzohary Mohamed
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Virologic Response ◽  
Hcv Rna ◽  
Occult Hepatitis ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Occult Hepatitis C ◽  
Direct Acting Antiviral Agents

Abstract Background Occult infection with hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes, despite constant negative results from tests for HCV RNA in serum. Objectives The aim of the study to detect the prevalence of occult hepatitis C Virus infection in patients who achieved a sustained virologic response (SVR) to direct-acting antiviral agents and to outline predictors of OCI. Patients and Methods This study included 100 patients with chronic HCV infection without liver cirrhosis attending to hepatitis C clinics at Ain Shams University Hospital, Ahmed Maher Teaching hospital and Elgomhorya Teaching Hospital.who received sofosbuvir (400mg) plus daclatasvir (60mg) daily for 12 weeks with or without ribavirin according to National committee to combat viral hepatitis (NCCVH) protocol. Results We tested peripheral blood for HCV RNA in PBMCs to detect OCI. Occult HCV was found positive in 12% of the studied cases. Occult HCV was positive more in male cases. Positive cases had significantly lower age, and higher total bilirubin, direct bilirubin, AST and ALT levels. Age had significant moderate diagnostic performance in predicting occult HCV, while direct bilirubin has significant low diagnostic performance in predicting occult HCV. Conclusion OCI following direct antiviral therapy may be present in some cases, and this may require further testing of patients with SVR particularly in younger male patients with persistantly high liver enzymes.

scholarly journals In VitroActivity and Resistance Profile of Samatasvir, a Novel NS5A Replication Inhibitor of Hepatitis C Virus

2014 ◽  
Vol 58 (8) ◽  
pp. 4431-4442 ◽  
Author(s):  
J. P. Bilello ◽  
L. B. Lallos ◽  
J. F. McCarville ◽  
M. La Colla ◽  
I. Serra ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Resistance Profile ◽  
Direct Acting Antiviral ◽  
Genotype 1A ◽  
Hcv Protease ◽  
Chronic Hcv ◽  
Direct Acting

ABSTRACTThe hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a clinically validated target for drugs designed to treat chronic HCV infection. This study evaluated thein vitroactivity, selectivity, and resistance profile of a novel anti-HCV compound, samatasvir (IDX719), alone and in combination with other antiviral agents. Samatasvir was effective and selective against infectious HCV and replicons, with 50% effective concentrations (EC50s) falling within a tight range of 2 to 24 pM in genotype 1 through 5 replicons and with a 10-fold EC50shift in the presence of 40% human serum in the genotype 1b replicon. The EC90/EC50ratio was low (2.6). A 50% cytotoxic concentration (CC50) of >100 μM provided a selectivity index of >5 × 107. Resistance selection experiments (with genotype 1a replicons) and testing against replicons bearing site-directed mutations (with genotype 1a and 1b replicons) identified NS5A amino acids 28, 30, 31, 32, and 93 as potential resistance loci, suggesting that samatasvir affects NS5A function. Samatasvir demonstrated an overall additive effect when combined with interferon alfa (IFN-α), ribavirin, representative HCV protease, and nonnucleoside polymerase inhibitors or the nucleotide prodrug IDX184. Samatasvir retained full activity in the presence of HIV and hepatitis B virus (HBV) antivirals and was not cross-resistant with HCV protease, nucleotide, and nonnucleoside polymerase inhibitor classes. Thus, samatasvir is a selective low-picomolar inhibitor of HCV replicationin vitroand is a promising candidate for future combination therapies with other direct-acting antiviral drugs in HCV-infected patients.

scholarly journals Impact of Preexisting Hepatitis C Virus Genotype 6 NS3, NS5A, and NS5B Polymorphisms on theIn VitroPotency of Direct-Acting Antiviral Agents

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Fiona McPhee ◽  
Joseph Ueland ◽  
Vincent Vellucci ◽  
Scott Bowden ◽  
William Sievert ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Virologic Response ◽  
Virus Genotype ◽  
Direct Acting Antiviral ◽  
East And Southeast Asia ◽  
Direct Acting ◽  
Ns3 Protease

ABSTRACTHCV genotype 6 (GT-6) is found predominantly in East and Southeast Asia. Clinical studies have focused on patients infected with hepatitis C virus (HCV) GT-6a, where high sustained virologic response (SVR) rates to direct-acting antivirals (DAAs) have been achieved. However, GT-6 is highly diverse, with 29 reported subtypes. We explored the diversity of GT-6 polymorphisms at residues associated with DAA resistance, their impact on DAAin vitropotency when evaluated in a GT-6a consensus replicon, and their association with specific GT-6 subtypes. GT-6 sequences from 25 patient-derived samples and 105 sequences from the U.S. HCV database were compared, and substitutions at resistance-associated residue positions were phenotyped against different DAAs. Preexisting resistance-associated substitutions (RASs) to NS3 protease (A156V and D168E) and NS5B nucleotide (L159F and S282C) inhibitors were rare (<4%). Preexisting RASs to NS5A inhibitors were common, especially at L28 (A/F/G/M/T/V) and R30 (E/N/S).In vitrosusceptibilities of NS5A-L28A and -L28T were dramatically reduced against all tested NS5A drugs (90% effective concentration [EC90] range, 119 to 2,032 nM) compared with susceptibilities against a GT-6a consensus replicon (EC90range, 0.1 to 19 nM). These L28 RASs preexisted in combination with R30S (EC90[L28A-R30S] of ≥720 nM or EC90[L28T-R30S] of ≥128 nM against tested DAAs) or as L28T-L31I (EC90[tested DAAs] of >5,000 nM) and were detected in evaluated GT-6b and -6f sequences. NS5A-L28A-R30A, observed in GT-6r, did not replicate. In conclusion, HCV GT-6b, GT-6f, and GT-6r sequences harbored highly resistant RASs to all evaluated NS5A drugs. Therefore, monitoring SVR in patients infected with these GT-6 subtypes treated with NS5A drug-containing regimens is suggested to confirm any association between noted NS5A polymorphisms and treatment failure.

scholarly journals Effect of Direct-Acting Antiviral Therapy on Thrombocytopenic Patients with Hepatitis C Virus-Related Chronic Liver Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Mahmoud Saif-Al-Islam ◽  
Usama M. Abdelaal ◽  
Mustafa Adel Younis ◽  
Hisham A. Alghany Algahlan ◽  
Safaa Khalaf
Keyword(s):  
Platelet Count ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatic Fibrosis ◽  
White Blood Cells ◽  
Advanced Fibrosis ◽  
Direct Acting Antiviral ◽  
Chronic Hcv ◽  
Direct Acting ◽  
A Prospective Study

Background and Aims. Thrombocytopenia is a common complication in patients with chronic hepatitis C virus (HCV) that increases the risk of bleeding. We aimed to analyze the hematologic effects of the new direct-acting antiviral (DAA) therapy, particularly on the platelet count in chronic HCV-infected patients with thrombocytopenia. Patients and Methods. One hundred thrombocytopenic patients chronically infected with HCV were included in a prospective study. All patients were eligible for receiving anti-HCV treatment with sofosbuvir-based regimens for 12 weeks, according to the protocol of the National Program for treatment of HCV in Egypt sponsored by the Ministry of Health. Results. At the end of treatment (EOT), there was a highly significant increase in platelet count ( p < 0.001 ), a significant increase in white blood cells (WBCs) count ( p ≤ 0.032 ), and a highly significant decrease in hemoglobin level ( p < 0.001 ) as compared to pretreatment levels. Patients with mild to moderate hepatic fibrosis had significantly higher median and interquartile range (IQR) platelet count at baseline and EOT than those with advanced fibrosis and cirrhosis ( p ≤ 0.023 and p < 0.001 , respectively). There was more elevation in platelet count at EOT in patients with mild to moderate fibrosis than those with advanced fibrosis and cirrhosis. Out of the hundred patients, 73% showed improvement of platelet count, while 27% showed no improvement or even decrease in the platelet count. Conclusion. Sofosbuvir-based DAA therapy is a highly effective and safe treatment regimen that results in the improvement of platelet count in thrombocytopenic patients, particularly in mild to moderate stages of hepatic fibrosis.

scholarly journals Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction

2017 ◽  
Vol 5 (1) ◽  
pp. 8-17 ◽  
Author(s):  
Ayman Geddawy ◽  
Yasmine F. Ibrahim ◽  
Nabil M. Elbahie ◽  
Mohammad A. Ibrahim
Keyword(s):  
Clinical Pharmacology ◽  
Drug Interaction ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Virologic Response ◽  
Hcv Infection ◽  
Major Advance ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction.

New Epidemiologic Data Regarding Hepatitis C Virus Infection in Romania

2017 ◽  
Vol 26 (4) ◽  
pp. 381-386
Author(s):  
Mircea Manuc ◽  
Carmen M. Preda ◽  
Corneliu P. Popescu ◽  
Cristian Baicuș ◽  
Theodor Voiosu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Users ◽  
Antiviral Agent ◽  
Virologic Response ◽  
Advanced Fibrosis ◽  
Direct Acting Antiviral ◽  
Genotype 1B ◽  
Direct Acting ◽  
End Stage

Background & Aims: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania.Methods: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address.Results: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanța (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramureș (8.8/105) (p<0.001).Conclusions: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta.Abbreviations: BMI: body mass index; DAA: direct-acting antiviral agent; GT: genotype; HBV: hepatitis B virus; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; IDU: intravenous drug users; MELD: model for end stage liver disease; NASH: non-alcoholic steatohepatitis; SVR; sustained virologic response.

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