Safety and efficacy of sofosbuvir based regimen in the treatment of hepatitis C virus infection among hemodialysis patients in Morocco

The introduction of a new class of drugs known as direct acting antiviral (DAA) agents represents a revolution in the treatment of hepatitis C virus (HCV) in the general population, as these regimens are associated with higher sustained virological response (SVR) rates and fewer side effects. However, for patients with advanced chronic kidney disease suffering from HVC infection, treatment options including DAA remain limited. The aim of this study is to report our experience on Sofosbuvir (SOF) based regimen in the treatment of HCV in hemodialysis patients. In this observational study, we included all patients with chronic HCV infection on hemodialysis who were treated with SOF in our Hospital between April 2016 and March 2018. All patients were treated with a combination of 400 mg of SOF three times a week after hemodialysis and of 60 mg of Daclatasvir daily for a total of 12 to 24 weeks. A total of 20 hemodialysis patients were included in this study. 12 were females and the mean age was 52.1 ± 15.5 years. 11 patients were infected with HCV genotypes 1b. All patients achieved SVR. Clinical and biological tolerance was very good for all patients and none of them had to discontinue treatment because of side effects or developed hepatobiliary and cardiac toxicity. Two patients reported fatigue and another patient reported headaches. However, these symptoms were spontaneously resolved after the end of the treatment. In Morocco, despite the absence of new DAA combination treatment regimens which are not renally eliminated, our study concludes that SOF based treatment without Ribavirin or Peginterferon was effective and safe with minimal side effects. However, larger studies are still needed in order to validate these results.

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Sa1525 – Visne Analysis of Hepatitis C Virus-Specific Cd8 T Cells from Direct Acting Antiviral-Treated Chronic Hcv Patients and Hcv Resolvers

Gastroenterology ◽

10.1016/s0016-5085(19)40073-5 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1232

Author(s):

Jihad Aljabban ◽

Pierre Tonnerre ◽

Dan Kvistad ◽

Max Robidoux ◽

Joelle Brown ◽

...

Keyword(s):

T Cells ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Cd8 T Cells ◽

Direct Acting Antiviral ◽

Chronic Hcv ◽

Direct Acting

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Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection

Journal of Clinical Medicine ◽

10.3390/jcm10020221 ◽

2021 ◽

Vol 10 (2) ◽

pp. 221

Author(s):

Pil Soo Sung ◽

Eui-Cheol Shin

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Hepatitis C Virus ◽

Hepatitis C ◽

De Novo ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting

Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, natural killer (NK) cells exhibited a deviant functional phenotype with decreased production of antiviral cytokines and increased cytotoxicity; however, DAA treatment rapidly decreased their cytotoxic function. Effective DAA therapy also suppressed the intrahepatic activation of macrophages/monocytes. This was followed by a decrease in mucosal-associated invariant T (MAIT) cell cytotoxicity without normalization of cytokine production. Rapid changes in the phenotypes of NK and MAIT cells after DAA treatment may attenuate the cytotoxicity of these cells against cancer cells. Moreover, DAA treatment did not normalize the increased frequencies of regulatory T cells even after clearance of HCV infection. Thus, the persistently increased frequency of regulatory T cells may contribute to a local immunosuppressive milieu and hamper the clearance of cancer cells. This review will focus on recent studies describing the changes in innate and adaptive immune responses after DAA treatment in patients with chronic HCV infection in the context of de novo occurrence or recurrence of HCC.

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New and Emerging Evidence on the Use of Second-Generation Direct Acting Antivirals for the Treatment of Hepatitis C Virus in Renal Impairment

Journal of Pharmacy Practice ◽

10.1177/0897190016632128 ◽

2016 ◽

Vol 30 (3) ◽

pp. 359-365 ◽

Cited By ~ 7

Author(s):

Maria A. Sorbera ◽

Michelle L. Friedman ◽

Rebecca Cope

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Kidney Disease ◽

Renal Impairment ◽

Second Generation ◽

Severe Renal Impairment ◽

Treatment Options ◽

Uncertain Data ◽

Treatment Regimens ◽

Direct Acting

Due to the intimate relationship between liver and kidney disease in hepatitis C virus (HCV) infection, treatment options for HCV-positive patients at any stage of chronic kidney disease (CKD) are essential. The availability of second-generation, direct-acting antiviral (DAA) combinations has allowed for the advent of interferon-sparing treatment regimens with shorter durations and minimal side effects. While many of the second-generation DAAs are principally metabolized by the hepatic system, dosing in severe renal impairment (creatinine clearance [CrCl] <30 mL/min) or dialysis has remained questionable due to limited experience. New evidence regarding the use of these agents in renal impairment continues to become available, as real-world experience with these treatment regimens is reported. Simeprevir, ledipasvir, paritaprevir, ombitasvir, dasabuvir, and daclatasvir have data to suggest safety in end-stage renal disease. While safety and efficacy with sofosbuvir remains uncertain, data are now available to support utilizing a dose adjustment when glomerular filtration rates are <30 mL/min. Upcoming regimens grazoprevir/elbasvir and daclatasvir/asunaprevir/beclavubir may provide further options for patients with advanced kidney disease, and ongoing studies will continue to provide guidance for this unique patient population. This article will review the currently available literature, including the newest emerging evidence, on the use of second-generation DAAs in CKD stages 3 to 5 and dialysis.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02777-13 ◽

2014 ◽

Vol 58 (8) ◽

pp. 4431-4442 ◽

Cited By ~ 22

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.

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Liver cT1 decreases following direct-acting antiviral therapy in patients with chronic hepatitis C virus

Abdominal Radiology ◽

10.1007/s00261-020-02860-5 ◽

2020 ◽

Author(s):

Arjun N. A. Jayaswal ◽

Christina Levick ◽

Jane Collier ◽

Elizabeth M. Tunnicliffe ◽

Matthew D. Kelly ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Liver Fibrosis ◽

Liver Fat ◽

Liver Ct ◽

Direct Acting Antiviral ◽

Chronic Hepatitis C Virus ◽

Chronic Hcv ◽

Direct Acting

Abstract Purpose Direct-acting antiviral therapies (DAAs) for treatment of chronic hepatitis C virus (HCV) have excellent rates of viral eradication, but their effect on regression of liver fibrosis is unclear. The primary aim was to use magnetic resonance imaging (MRI) and spectroscopy (MRS) to evaluate changes in liver fibrosis, liver fat and liver iron content (LIC) in patients with chronic HCV following treatment with DAAs. Methods In this prospective study, 15 patients with chronic HCV due to start treatment with DAAs and with transient elastography (TE) > 8 kPa were recruited consecutively. Patients underwent MRI and MRS at baseline (before treatment), and at 24 weeks and 48 weeks after the end of treatment (EoT) for the measurement of liver cT1 (fibroinflammation), liver fat and T2* (LIC). Results All patients achieved a sustained virological response. Liver cT1 showed significant decreases from baseline to 24 weeks post EoT (876 vs 806 ms, p = 0.002, n = 15), baseline to 48 weeks post EoT (876 vs 788 ms, p = 0.0002, n = 13) and 24 weeks post EoT to 48 weeks post EoT (806 vs 788 ms, p = 0.016, n = 13). Between baseline and 48 weeks EoT significant reduction in liver fat (5.17% vs 2.65%, p = 0.027) and an increase in reported LIC (0.913 vs 0.950 mg/g, p = 0.021) was observed. Conclusion Liver cT1 decreases in patients with chronic HCV undergoing successful DAA treatment. The relatively fast reduction in cT1 suggests a reduction in inflammation rather than regression of fibrosis.

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Hepatitis C Virus: A Critical Appraisal of New Approaches to Therapy

Hepatitis Research and Treatment ◽

10.1155/2012/138302 ◽

2012 ◽

Vol 2012 ◽

pp. 1-21

Author(s):

David R. Nelson ◽

Donald M. Jensen ◽

Mark S. Sulkowski ◽

Greg Everson ◽

Michael W. Fried ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Comprehensive Evaluation ◽

Antiviral Agents ◽

The United States ◽

Current Data ◽

New Era ◽

Direct Acting Antiviral ◽

Treatment Regimens ◽

Direct Acting

The HCV council 2011 convened 11 leading clinicians and researchers in hepatitis C virus from academic medical centers in the United States to provide a forum for the practical and comprehensive evaluation of current data regarding best practices for integrating new direct-acting antiviral agents into existing treatment paradigms. The council investigated 10 clinical practice statements related to HCV treatment that reflect key topical areas. Faculty members reviewed and discussed the data related to each statement, and voted on the nature of the evidence and their level of support for each statement. In this new era of DAAs, a comprehensive and critical analysis of the literature is needed to equip clinicians with the knowledge necessary to design, monitor, and modify treatment regimens in order to optimize patient outcomes.

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Simplification of Care for Chronic Hepatitis C Virus Infection

Seminars in Liver Disease ◽

10.1055/s-0040-1713657 ◽

2020 ◽

Vol 40 (04) ◽

pp. 392-402 ◽

Cited By ~ 1

Author(s):

Jean-Michel Pawlotsky ◽

Christian B. Ramers ◽

John F. Dillon ◽

Jordan J. Feld ◽

Jeffrey V. Lazarus

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Scale Up ◽

Linkage To Care ◽

World Health ◽

Direct Acting Antiviral ◽

Hcv Screening ◽

Health Organization ◽

Chronic Hcv ◽

Direct Acting

AbstractIn 2016, the World Health Organization (WHO) set a target for eliminating viral hepatitis as a major public health threat by 2030. However, while today's highly effective and well-tolerated pangenotypic direct-acting antiviral regimens have maximized simplification of hepatitis C virus (HCV) treatment, there remain a plethora of barriers to HCV screening, diagnosis, and linkage to care. As of 2017, only 19% of the estimated 71 million individuals living with chronic HCV worldwide were diagnosed and in 2015 to 2016, only 21% of diagnosed individuals had accessed treatment. Simplification and decentralization of the HCV care cascade would bolster patient engagement and support the considerable scale-up needed to achieve WHO targets. Recent developments in HCV screening and diagnosis, together with reduced pretreatment assessment and on-treatment monitoring requirements, can further streamline the care continuum, ensuring patients are linked to care quickly and earlier in the disease course, and minimize clinic visits.

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

Egyptian Liver Journal ◽

10.1186/s43066-021-00124-5 ◽

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.

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Hepatitis C Virus Infection in Maintenance Hemodialysis Patients: Recommendations for Diagnostics and Treatment

The International Journal of Artificial Organs ◽

10.5301/ijao.5000548 ◽

2016 ◽

Vol 39 (12) ◽

pp. 590-595 ◽

Cited By ~ 1

Author(s):

Pavlina Dzekova-Vidimliski ◽

Aleksandar Sikole

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Treatment ◽

Antiviral Agents ◽

Hemodialysis Patients ◽

Maintenance Hemodialysis ◽

Direct Acting Antivirals ◽

Hcv Treatment ◽

Direct Acting Antiviral ◽

Direct Acting

Hepatitis C virus (HCV) infection is highly prevalent among patients treated with maintenance hemodialysis and is an important cause of morbidity and mortality. It is necessary to determine the HCV genotype and the viral load to monitor the clinical and laboratory features and to establish an optimal antiviral treatment strategy. Antiviral treatments are presented with a standard interferon-based regimen and new direct-acting antiviral agents. The advent of direct-acting antivirals has improved the efficacy and safety of HCV treatment for most patients, even in difficult-to-treat populations such as patients on hemodialysis. HCV treatment with direct-acting antivirals in hemodialysis patients is highly effective, with viral eradication rates similar to those seen in patients without chronic kidney disease and with acceptable adverse event profiles.

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The efficacy and safety of direct-acting antiviral drugs in the management of hepatitis C virus-related arthritis

Egyptian Rheumatology and Rehabilitation ◽

10.1186/s43166-020-00021-6 ◽

2020 ◽

Vol 47 (1) ◽

Author(s):

Samah M. Alian ◽

Mohamed Othman Wahba ◽

Ahmed Fathy Gomaa ◽

Sahar S. Khalil

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Viral Response ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Group I ◽

Group Ii ◽

Chronic Hcv ◽

Direct Acting ◽

Post Therapy

Abstract Background Hepatitis C virus (HCV) infection is a worldwide disease. HCV-related arthritis is one of the extrahepatic manifestations of the disease. The treatment of chronic HCV has been revolutionized with the introduction of oral direct-acting antiviral (DAA) drugs. We aim to determine the outcomes of treatment by the combination of sofosbuvir-daclatasvir with or without ribavirin in patients with HCV-related arthritis. Results Post-therapy, all group I patients had sustained viral response. Significant improvement of the outcome parameters was found 12 weeks post-treatment in group I compared to baseline and group II. Complete and partial remission of articular symptoms in group I patients was observed in 80% and 5%, respectively, while 85% of patients in group II showed no remission. Few mild side effects were encountered with therapy. Conclusion The combination of sofosbuvir-daclatasvir with or without ribavirin is an effective and safe therapy for eradication of HCV infection and amelioration of HCV-related arthritis.

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