scholarly journals Interferon Response in Hepatitis C Virus-Infected Hepatocytes: Issues to Consider in the Era of Direct-Acting Antivirals

2020 ◽  
Vol 21 (7) ◽  
pp. 2583 ◽  
Author(s):  
Pil Soo Sung ◽  
Eui-Cheol Shin
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Virus ◽  
High Rate ◽  
Interferon Response ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Global Population ◽  
Open Issues

When interferons (IFNs) bind to their receptors, they upregulate numerous IFN-stimulated genes (ISGs) with antiviral and immune regulatory activities. Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus that affects over 71 million people in the global population. Hepatocytes infected with HCV produce types I and III IFNs. These endogenous IFNs upregulate a set of ISGs that negatively impact the outcome of pegylated IFN-α and ribavirin treatments, which were previously used to treat HCV. In addition, the IFNL4 genotype was the primary polymorphism responsible for a suboptimal treatment response to pegylated IFN-α and ribavirin. However, recently developed direct-acting antivirals have demonstrated a high rate of sustained virological response without pegylated IFN-α. Herein, we review recent studies on types I and III IFN responses in HCV-infected hepatocytes. In particular, we focused on open issues related to IFN responses in the direct-acting antiviral era.

scholarly journals Hepatitis C virus vaccine development: old challenges and new opportunities

2015 ◽  
Vol 2 (3) ◽  
pp. 285-295 ◽  
Author(s):  
Dapeng Li ◽  
Zhong Huang ◽  
Jin Zhong
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Vaccine Development ◽  
Rna Virus ◽  
Antiviral Agents ◽  
Resistance Mutations ◽  
Direct Acting Antiviral ◽  
Direct Acting

Abstract Hepatitis C virus (HCV), an enveloped positive-sense single-stranded RNA virus, can cause chronic and end-stage liver diseases. Approximately 185 million people worldwide are infected with HCV. Tremendous progress has been achieved in the therapeutics of chronic hepatitis C thanks to the development of direct-acting antiviral agents (DAAs), but the worldwide use of these highly effective DAAs is limited due to their high treatment cost. In addition, drug-resistance mutations remain a potential problem as DAAs are becoming a standard therapy for chronic hepatitis C. Unfortunately, no vaccine is available for preventing new HCV infection. Therefore, HCV still imposes a big threat to human public health, and the worldwide eradication of HCV is critically dependent on an effective HCV vaccine. In this review, we summarize recent progresses on HCV vaccine development and present our views on the rationale and strategy to develop an effective HCV vaccine.

scholarly journals Successful retreatment of HCV relapse patient with 4 weeks long sofsobuvir, ribavirin, and daclatasvir combination: Case Series

2020 ◽  
Vol 2 (3) ◽  
pp. 17-25
Author(s):  
Komal Saleem ◽  
Amjad Ali ◽  
Shazia Rafique ◽  
Noshaba Rani ◽  
Braira Wahid
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Therapy ◽  
Virological Response ◽  
Interferon Therapy ◽  
Rna Virus ◽  
Case Series ◽  
Pakistani Population ◽  
Direct Acting Antiviral ◽  
Direct Acting

Hepatitis-C virus (HCV) is an enveloped RNA virus that currently infects more than 180 million people, worldwide. Interferon therapy was previously used as a standard therapy for HCV. Now it has been replaced with an interferon-free therapy or the direct acting antiviral (DAA) drug therapy. Although the DAA drug therapy is a potent strategy which has an excellent efficacy against the HCV infection with a majority of patients achieving sustained virological response (SVR), we report here three patients who experienced relapse after a 6-month long DAA drug therapy. The patients experienced relapse after receiving sofosbuvir (400mg) and ribavirin for 6 months. All three patients were later successfully treated with sofosbuvir, ribavirin, and daclatasvir combination. The current study highlights that the retreatment combination of sofosbuvir, ribavirin, and daclatasvir is more efficacious in the Pakistani population where practitioners are still using sofosbuvir and ribavirin.

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection

2019 ◽  
Vol 38 (3) ◽  
pp. 232-239 ◽  
Author(s):  
Vijay Gayam ◽  
Oluwole Jegede ◽  
Benjamin Tiongson ◽  
Amrendra Kumar Mandal ◽  
Jasdeep Sidhu ◽  
...  
Keyword(s):  
Substance Use ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Psychiatric Disorders ◽  
Treatment Response ◽  
Psychiatric Diagnosis ◽  
Psychiatric Patients ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Direct Acting

Background: The highest burden of hepatitis C virus (HCV) infection is seen in patients with psychiatric disorders who have been excluded from traditional treatments with Interferon due to treatment-emergent neuropsychiatric adverse effects. The goal of this study is to determine the tolerability, treatment retention, and efficacy of direct-acting antivirals with psychiatric disorders and comorbid substance use disorders in real-life settings. Methods: This is a retrospective cohort observational study of HCV patients treated with direct-acting antivirals between January 2016 and December 2018. Patients were stratified and sub-stratified based on their psychiatric diagnosis and substance use. The primary assessment was the sustained virologic response at 12 weeks post-treatment (SVR12). Results: Among the 291 patients analyzed, patients with psychiatric diagnosis and non-psychiatric patients made up 51.2% (n = 149) and 48.8% (n = 142) respectively. Majority of the patients included in the study were African-Americans (68.7%, n = 200). Overall, 95.3% (142/149) and 94.4% (134/142) of psychiatric and non-psychiatric patients, respectively, achieved SVR12 and treatment response was similar between the groups (p = 0.72). Among psychiatric patients, only the prior treatment status was identified as a predictor of treatment response (OR 0.153, 95% CI 0.03–0.79; p = 0.05). No statistical difference was observed among the patients with SVR12 based on their primary psychiatric diagnoses or by comorbid substance abuse. Conclusion: The results of our study show that direct-acting antiviral treatments are well tolerated in psychiatric patients, and an overwhelming majority of patients achieved SVR12. Our study highlights the need to integrate HCV screening with treatment linkage in psychiatry and primary care practice.

scholarly journals Hepatitis C Virus and Hepatocellular Carcinoma: Pathogenetic Mechanisms and Impact of Direct-Acting Antivirals

2018 ◽  
Vol 12 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Ivan Schietroma ◽  
Giuseppe Corano Scheri ◽  
Claudia Pinacchio ◽  
Maura Statzu ◽  
Arnolfo Petruzziello ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Infection ◽  
The United States ◽  
Epidemiological Studies ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Hcc Recurrence

Introduction:Globally, between 64 and 103 million people are chronically infected with Hepatitis C virus (HCV), with more than 4.6 million people in the United States and is associated with more than 15.000 deaths annually. Chronic infection can result in cirrhosis and hepatocellular carcinoma.Explanation:Epidemiological studies have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC), mainly through chronic inflammation, cell deaths, and proliferation. Despite the new direct-acting antiviral drugs (DAA’s) being able to clear the HCV, HCC recurrence rate in these patients is still observed.Conclusion:In this review we highlighted some aspects that could be involved in the onset of HCV-induced HCC such as immune system, viral factors and host genetics factors.Moreover, we focused on some of the last reports about the effects of DAA’s on the HCV clearance and their potential implications in HCC recurrence.

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

2016 ◽  
Vol 39 (12) ◽  
pp. 590-595 ◽  
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.

scholarly journals Hypovascular tumors developed into hepatocellular carcinoma at a high rate despite the elimination of hepatitis C virus by direct-acting antivirals

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0237475
Author(s):  
Kazuaki Tabu ◽  
Seiichi Mawatari ◽  
Kohei Oda ◽  
Kotaro Kumagai ◽  
Yukiko Inada ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Rate ◽  
Direct Acting Antivirals ◽  
Direct Acting

A hepatitis C-vírus-bázispolimorfizmus jelentősége a kezelésben

2015 ◽  
Vol 156 (21) ◽  
pp. 849-854 ◽  
Author(s):  
István Tornai
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
First Generation ◽  
Pegylated Interferon ◽  
Direct Acting Antivirals ◽  
Direct Acting Antiviral ◽  
Genotype 1A ◽  
Direct Acting ◽  
Ns5b Polymerase

The treatment of chronic hepatitis C has developed significantly during the last 25 years. In patients with genotype 1 infection 40–50% sustained virologic response could be achieved using pegylated interferon and ribavirin dual combination, which could be increased significantly with the introduction of direct acting antivirals. Three major groups of direct acting antivirals are known, which directly inhibit different phases of viral life cycle, by inhibiting the function of several non-structural proteins (NS3/4A protease, NS5A protein and NS5B polymerase). Due to the rapid replication rate of hepatitis C virus and the error-prone NS5B polymerase activity, mutant virions are generated, which might have reduced susceptibility to direct acting antiviral therapy. Since these resistance associated variants might exist before the antiviral therapy, they are still able to replicate during the direct acting antiviral treatment. Due to this selection pressure, the resistant virus will replace the wild type. This was especially detected during monotherapy, therefore, the first generation of direct acting antivirals have been combined with pegylated interferon and ribavirin, while recently interferon-free combinations are being developed including 2 or 3 direct acting antivirals. Using the first generation protease inhibitors boceprevir and telaprevir, it could have been seen, that the rate of resistance associated variants is higher and the therapeutic outcome is worse in patients with hepatitis C virus genotype 1a, than in 1b. Similar phenomenon was seen with the second generation of NS3/4A protease inhibitors as well as with NS5A or NS5B polymerase. This is due to the lower genetic barrier to resistance, ie. usually fewer mutations are enough for the emergence of resistance in genotype 1a. The selection of resistance associated variants is one of the most important challenges during the interferon-free therapy. Orv. Hetil., 2015, 156(21), 849–854.

scholarly journals Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Eric R. Yoo ◽  
Ryan B. Perumpail ◽  
George Cholankeril ◽  
Aijaz Ahmed
Keyword(s):  
Down Syndrome ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Direct Acting Antivirals ◽  
Hepatitis C Infection ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
Favorable Safety

Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

scholarly journals Successful retreatment of HCV relapse patient with 4 weeks long sofsobuvir, ribavirin, and daclatasvir combination: Case Series

2020 ◽  
Vol 2 (3) ◽  
pp. 17-25
Author(s):  
Komal Saleem ◽  
Amjad Ali ◽  
Shazia Rafique ◽  
Noshaba Rani ◽  
Braira Wahid
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Therapy ◽  
Virological Response ◽  
Interferon Therapy ◽  
Rna Virus ◽  
Case Series ◽  
Pakistani Population ◽  
Direct Acting Antiviral ◽  
Direct Acting

Hepatitis-C virus (HCV) is an enveloped RNA virus that currently infects more than 180 million people, worldwide. Interferon therapy was previously used as a standard therapy for HCV. Now it has been replaced with an interferon-free therapy or the direct acting antiviral (DAA) drug therapy. Although the DAA drug therapy is a potent strategy which has an excellent efficacy against the HCV infection with a majority of patients achieving sustained virological response (SVR), we report here three patients who experienced relapse after a 6-month long DAA drug therapy. The patients experienced relapse after receiving sofosbuvir (400mg) and ribavirin for 6 months. All three patients were later successfully treated with sofosbuvir, ribavirin, and daclatasvir combination. The current study highlights that the retreatment combination of sofosbuvir, ribavirin, and daclatasvir is more efficacious in the Pakistani population where practitioners are still using sofosbuvir and ribavirin.

Sign in / Sign up

Export Citation Format

Share Document