scholarly journals Hepatitis C Virus NS3 Inhibitors: Current and Future Perspectives

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Kazi Abdus Salam ◽  
Nobuyoshi Akimitsu
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protease Inhibitors ◽  
Standard Of Care ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Hcv Infection ◽  
Main Concern ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting

Currently, hepatitis C virus (HCV) infection is considered a serious health-care problem all over the world. A good number of direct-acting antivirals (DAAs) against HCV infection are in clinical progress including NS3-4A protease inhibitors, RNA-dependent RNA polymerase inhibitors, and NS5A inhibitors as well as host targeted inhibitors. Two NS3-4A protease inhibitors (telaprevir and boceprevir) have been recently approved for the treatment of hepatitis C in combination with standard of care (pegylated interferon plus ribavirin). The new therapy has significantly improved sustained virologic response (SVR); however, the adverse effects associated with this therapy are still the main concern. In addition to the emergence of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase portion of the HCV NS3 protein. This review article summarizes our current understanding of HCV treatment, particularly with those of NS3 inhibitors.

scholarly journals Benefits From Sustained Virologic Response to Pegylated Interferon Plus Ribavirin in HIV/Hepatitis C Virus–Coinfected Patients With Compensated Cirrhosis

2013 ◽  
Vol 56 (11) ◽  
pp. 1646-1653 ◽  
Author(s):  
José A. Mira ◽  
Antonio Rivero-Juárez ◽  
Luis F. López-Cortés ◽  
José A. Girón-González ◽  
Francisco Téllez ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Compensated Cirrhosis ◽  
Pegylated Interferon Plus Ribavirin

Viral Hepatitis C: Treatment

2018 ◽  
Author(s):  
Jay Luther ◽  
Raymond T. Chung ◽  
Anna Lidofsky ◽  
Jacinta A Holmes ◽  
Stephanie M Rutledge
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Viral Hepatitis C ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Infection with the hepatitis C virus (HCV) leads to chronic infection in the majority, and is associated with the development of complications including cirrhosis, end-stage liver failure, hepatocellular carcinoma and death. HCV is curable, and successful viral eradication is associated with a reduction in cirrhosis and liver-related mortality. However, previous HCV therapy, consisting of pegylated interferon plus ribavirin, was associated with poor cure rates and significant adverse events. The development of direct-acting antiviral agents (DAAs) that specifically target HCV replication has revolutionized the treatment of HCV. Current regimens are now highly potent, all-oral, interferon-free combinations of these DAAs. The Food and Drug Administration has now approved many of these regimens. The changing management of HCV infection, including recent advances in HCV therapy, are discussed. This review contains 1 figure, 5 tables and 59 references Key words: direct-acting antiviral agents, hepatitis C virus, interferon-free therapy, management, treatment

scholarly journals Recurrence of Hepatitis C Virus after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab, Pakistan.

2020 ◽  
Author(s):  
Muhammad Naeem Raza ◽  
Kalsoom Sughra ◽  
Nadia Zeeshan
Keyword(s):  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Optimal Strategies ◽  
Pegylated Interferon ◽  
Virologic Response ◽  
Direct Acting Antivirals ◽  
Correct Treatment ◽  
Medical College ◽  
Direct Acting

Abstract Background Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Pakistan.Methods This study conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan from July 2017 to January 2019. Total 973 patients administered the recommended dose that divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied.Results The 374 patients given interferon therapy and 32 of 374 were positive after 24 weeks of treatment. Among these 29 patients have same genotype and recurrence was present .While 3 patients were re-infected with different HCV strains. In case of DAAs, only 27 patients were positive among 558 patients after 2 weeks and only one patient re-infected with different genotype. Early and sustained virologic response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon.Conclusion SVR appears in DAAs and recurrence rate was high in interferon-based therapy as compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select optimal strategies for retreatment cases.

Viral Hepatitis C: Treatment

2018 ◽  
Author(s):  
Jay Luther ◽  
Raymond T. Chung ◽  
Anna Lidofsky ◽  
Jacinta A Holmes ◽  
Stephanie M Rutledge
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Viral Hepatitis C ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Infection with the hepatitis C virus (HCV) leads to chronic infection in the majority, and is associated with the development of complications including cirrhosis, end-stage liver failure, hepatocellular carcinoma and death. HCV is curable, and successful viral eradication is associated with a reduction in cirrhosis and liver-related mortality. However, previous HCV therapy, consisting of pegylated interferon plus ribavirin, was associated with poor cure rates and significant adverse events. The development of direct-acting antiviral agents (DAAs) that specifically target HCV replication has revolutionized the treatment of HCV. Current regimens are now highly potent, all-oral, interferon-free combinations of these DAAs. The Food and Drug Administration has now approved many of these regimens. The changing management of HCV infection, including recent advances in HCV therapy, are discussed. This review contains 1 figure, 5 tables and 59 references Key words: direct-acting antiviral agents, hepatitis C virus, interferon-free therapy, management, treatment

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 Host-targeting therapies for hepatitis C virus infection: current developments and future applications

2018 ◽  
Vol 11 ◽  
pp. 175628481875948 ◽  
Author(s):  
Emilie Crouchet ◽  
Florian Wrensch ◽  
Catherine Schuster ◽  
Mirjam B. Zeisel ◽  
Thomas F. Baumert
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Potential Role ◽  
Standard Of Care ◽  
Virologic Response ◽  
Host Proteins ◽  
The Past ◽  
Direct Acting ◽  
Complementary Mechanism ◽  
Therapy Treatment

Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases and hepatocellular carcinoma (HCC) worldwide. In the past few years, anti-HCV therapies have undergone a revolution with the approval of multiple direct-acting antivirals (DAAs), which enable interferon-free treatments with considerable improvement of sustained virologic response in patients. Today, DAAs have become the standard of care for HCV therapy. However, several limitations remain, which include access to therapy, treatment failure in a subset of patients and persistent risk of HCC development following cure in patients with advanced fibrosis. By targeting conserved host proteins involved in the HCV life cycle, host-targeting agents (HTAs) offer opportunities for pan-genotypic antiviral approaches with a high barrier to drug resistance. Moreover, when applied in combination with DAAs, HTAs could improve the management of difficult-to-treat patients by acting through a complementary mechanism of action. In this review, we summarize the different HTAs evaluated in preclinical and clinical development and discuss their potential role for anti-HCV therapies.

Viral Hepatitis C: Treatment

2018 ◽  
Author(s):  
Jay Luther ◽  
Raymond T. Chung ◽  
Anna Lidofsky ◽  
Jacinta A Holmes ◽  
Stephanie M Rutledge
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Pegylated Interferon ◽  
Direct Acting Antiviral ◽  
Hcv Therapy ◽  
Viral Hepatitis C ◽  
Pegylated Interferon Plus Ribavirin ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Infection with the hepatitis C virus (HCV) leads to chronic infection in the majority, and is associated with the development of complications including cirrhosis, end-stage liver failure, hepatocellular carcinoma and death. HCV is curable, and successful viral eradication is associated with a reduction in cirrhosis and liver-related mortality. However, previous HCV therapy, consisting of pegylated interferon plus ribavirin, was associated with poor cure rates and significant adverse events. The development of direct-acting antiviral agents (DAAs) that specifically target HCV replication has revolutionized the treatment of HCV. Current regimens are now highly potent, all-oral, interferon-free combinations of these DAAs. The Food and Drug Administration has now approved many of these regimens. The changing management of HCV infection, including recent advances in HCV therapy, are discussed. This review contains 1 figure, 5 tables and 59 references Key words: direct-acting antiviral agents, hepatitis C virus, interferon-free therapy, management, treatment

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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