Effects of daclatasvir: A Synthesis of Findings from 27 Studies

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Original Abstract of the Article

Major Research Findings

Daclatasvir is a direct-acting antiviral (DAA) medication used to treat chronic hepatitis C. Studies have shown that daclatasvir, particularly in combination therapies, demonstrates high efficacy in achieving sustained virological response (SVR), with rates exceeding 90%. 18 , 6 , 3 , 25 , 12 Notably, daclatasvir has shown remarkable efficacy against genotype 1b of the hepatitis C virus (HCV), with several studies indicating its superior effectiveness compared to single-agent daclatasvir treatments. 2 Furthermore, daclatasvir has been found to be highly effective when used in combination with sofosbuvir. 4 , 8 , 11 Additionally, research suggests that daclatasvir can reverse cellular alterations associated with HCV infection. 20 Daclatasvir has also been shown to improve changes in immune markers caused by HCV infection, although more research is needed to fully understand its impact on immune system restoration. 15

On the other hand, it is crucial to note that daclatasvir can inhibit CYP3A4, a liver enzyme involved in drug metabolism. This means that it can potentially interact with other medications, requiring careful consideration during treatment. 23

Benefits and Risks

Benefit Summary

Daclatasvir has demonstrated high efficacy in treating chronic hepatitis C, achieving sustained virological response (SVR) rates exceeding 90%. 18 , 6 , 3 , 25 , 12 Daclatasvir, particularly in combination therapies, has shown remarkable efficacy against genotype 1b of the hepatitis C virus (HCV). 2 Daclatasvir has also been found to be highly effective when used in combination with sofosbuvir. 4 , 8 , 11 Daclatasvir has been shown to reverse cellular alterations associated with HCV infection. 20 Additionally, daclatasvir has been shown to improve changes in immune markers caused by HCV infection. 15

Risk Summary

Daclatasvir can inhibit CYP3A4, a liver enzyme involved in drug metabolism, which can potentially interact with other medications. 23

Comparison of Studies

Similarities

Many studies have reported that daclatasvir, especially in combination therapies, is highly effective in treating chronic hepatitis C, achieving sustained virological response (SVR) rates exceeding 90%. 18 , 6 , 3 , 25 , 12

Differences

While some studies have shown that daclatasvir can reverse cellular alterations associated with HCV infection, this effect is not consistently observed in all studies. 20 Furthermore, although daclatasvir has been shown to improve changes in immune markers caused by HCV infection, the extent of its impact on immune system restoration requires further investigation. 15

Consistency and Contradictions in Findings

The majority of research consistently demonstrates the high efficacy of daclatasvir-based DAA treatment in managing chronic hepatitis C. 18 , 6 , 3 , 25 , 12 However, information regarding potential side effects and drug interactions with daclatasvir remains limited. 23

Practical Implications

Daclatasvir-based DAA treatment offers an effective option for managing chronic hepatitis C. However, due to the possibility of side effects and drug interactions, it is essential to use this medication under the guidance of a medical professional. 23

Limitations of Current Research

Further research on daclatasvir is warranted, particularly concerning its long-term safety and efficacy. 18 , 6 , 3 , 25 , 12 Moreover, a deeper understanding of its mechanism of action and potential drug interactions is needed. 23

Future Research Directions

Future research should focus on the long-term safety and efficacy of daclatasvir, as well as its mechanism of action and potential drug interactions. 18 , 6 , 3 , 25 , 12 Research on the appropriate indications for daclatasvir-based DAA treatment and optimizing treatment methods is also crucial. 23

Conclusion

Daclatasvir has emerged as a promising treatment option for chronic hepatitis C. 18 , 6 , 3 , 25 , 12 However, due to the potential for side effects and drug interactions, it is crucial to use it under the guidance of a healthcare professional. 23 Future research on the long-term safety and efficacy of daclatasvir is essential for further understanding its role in managing chronic hepatitis C. 18 , 6 , 3 , 25 , 12

Literature analysis of 27 papers
Positive Content
24
Neutral Content
2
Negative Content
1
Article Type
1
1
1
0
27
2.

Symmetric benzidine derivatives as anti-HCV agents: Insight into the nature, stereochemistry of the capping amino acid and the size of the terminal capping carbamates.

Author: Abdel KarimShereen E, YoussefYoussef H, Abdel-HalimMohammad, FrakolakiEfseveia, VassilakiNiki, ZoidisGrigoris, AhmedNermin S, AbadiAshraf H

HCV inhibition
High SI50
Safe profile

A novel symmetric molecule, compound 4, bearing a benzidine prolinamide core, is a potent inhibitor of HCV 1b with high safety profile.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Drug repurposing through virtual screening and in vitro validation identifies tigecycline as a novel putative HCV polymerase inhibitor.

Author: ElHefnawiMahmoud, JoEunji, TolbaMahmoud M, FaresMohamed, YangJaewon, ShahbaazMohd, WindischMarc P

HCV inhibition

Tigecycline, a commonly used antibiotic, has shown potential as a repurposed drug for treating hepatitis C virus (HCV) infection. In vitro studies showed that tigecycline inhibited HCV RdRp and displayed synergistic effects with sofosbuvir and daclatasvir.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir.

Author: JockuschSteffen, TaoChuanjuan, LiXiaoxu, ChienMinchen, KumarShiv, MorozovaIrina, KalachikovSergey, RussoJames J, JuJingyue

COVID-19 treatment

Sofosbuvir is a drug that was originally developed to treat hepatitis C. This study found that Sofosbuvir can also inhibit the replication of SARS-CoV-2, the virus that causes COVID-19. The study suggests that Sofosbuvir could be used as a treatment for COVID-19, either alone or in combination with other drugs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Safety and effectiveness of direct-acting antivirals in patients with chronic hepatitis C and chronic kidney disease.

Author: RyuJi Eun, SongMyeong Jun, KimSeok-Hwan, KwonJung Hyun, YooSun Hong, NamSoon Woo, NamHee Chul, KimHee Yeon, KimChang Wook, YangHyun, BaeSi Hyun, SongDo Seon, ChangU Im, YangJin Mo, LeeSung Won, LeeHae Lim, LeeSoon Kyu, SungPil Soo, JangJeong Won, ChoiJong Young, YoonSeung Kew

DAAs benefits
HCV treatment
Renal function preservation

Direct acting antivirals (DAAs) showed comparable sustained virologic response at week 12 after treatment (SVR12) and safety in chronic kidney disease (CKD) patients with hepatitis C virus (HCV) infection compared to patients with stage 1 and 2. The effectiveness and safety of DAAs may be related to the treatment duration.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.

Language : English

8.

Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection.

Author: SokhelaSimiso, BoschBronwyn, HillAndrew, SimmonsBryony, WoodsJoana, JohnstoneHilary, AkpomiemieGodspower, EllisLeah, OwenAndrew, CasasCarmen Perez, VenterWillem Daniel Francois

SARS-CoV-2 prevention

The COVER trial aimed to assess the effectiveness of nitazoxanide or sofosbuvir/daclatasvir in reducing the risk of SARS-CoV-2 infection.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Clinical outcomes of sofosbuvir-based antivirals in patients with COVID-19: a systematic review and meta-analysis of randomized trials.

Author: KowChia Siang, JavedAmaan, RamachandramDinesh, HasanSyed Shahzad

Reduced mortality

Sofosbuvir-based direct-acting antiviral agents reduced the risk of mortality but not the development of severe illness in patients with COVID-19.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

14.

A novel substitution in NS5A enhances the resistance of hepatitis C virus genotype 3 to daclatasvir.

Author: Fernandes CamposGuilherme Rodrigues, WardJoseph, ChenShucheng, BittarCintia, Vilela RodriguesJoão Paulo, MartinelliAna de Lourdes Candolo, SouzaFernanda Fernandes, PereiraLeonardo Régis Leira, RahalPaula, HarrisMark

HCV resistance understanding
DAA resistance development

This study investigated the effect of a novel NS5A substitution (S98G) on replication fitness and resistance to DAAs in hepatitis C virus genotype 3. The S98G substitution, in combination with the previously characterized resistance-associated substitution (RAS), Y93H, resulted in a significant increase in daclatasvir resistance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

Remodeling of immunological biomarkers in patients with chronic hepatitis C treated with direct-acting antiviral therapy.

Author: RibeiroIsabela Gomes, Coelho-Dos-ReisJordana Grazziela Alves, FradicoJordana Rodrigues Barbosa, Costa-RochaIsmael Artur da, SilvaLuciana Diniz, FonsecaLucy Ana Dos Santos, StancioliRhaissa Carvalho Said, Teixeira-CarvalhoAndréa, Martins-FilhoOlindo Assis, TeixeiraRosângela

HCV treatment
Immune restoration

DAAs, a new treatment for hepatitis C, allow us to observe immune system changes caused by rapid viral replication suppression. A study of 50 patients showed that DAA treatment significantly reduced levels of several biomarkers associated with inflammation. The study also found that high ALT levels, low platelet count, and cirrhosis at the start of treatment were associated with delayed immune response recovery. These findings provide valuable insights into the immune restoration process triggered by DAA therapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Serum GP88 as a predictive biomarker for hepatocellular carcinoma in patients with viral hepatitis C after direct-acting antiviral agents.

Author: IshidaHidekazu, TakemuraMasao, SuetsuguAtsushi, NaikiTakafumi, TanakaTakuji, EiichiTomita, SerreroGinette, MatsunamiHidetoshi, YamamotoYasuko, SaitoKuniaki

Progranulin (GP88) is a growth factor involved in tumorigenesis and survival. This study investigated the potential of serum GP88 concentrations as a predictive biomarker for hepatocellular carcinoma in patients with viral hepatitis C after direct-acting antiviral treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Genetic Subtypes and Natural Resistance Mutations in HCV Genotype 4 Infected Saudi Arabian Patients.

Author: Di StefanoMariantonietta, IsmailMona H, LeitnerThomas, FaleoGiuseppina, Elmnan AdemSaada A, ElaminMohamed O M E, EltreifiObeidi, AlwazzehMarwan J, FioreJose R, SantantonioTeresa A

HCV treatment
Treatment failure

This study analyzed the genetic subtypes of hepatitis C virus (HCV) and the presence of resistance-associated substitutions (RASs) in a cohort of Saudi Arabian patients. The findings revealed that GT 4a was the most prevalent subtype, with RASs identified in 35% of patients. While treatment with sofosbuvir plus daclatasvir resulted in sustained virological response (SVR) in most patients, one patient carrying NS3-RAS V170I relapsed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

21.

Evaluation of the Binding Affinity of Anti-Viral Drugs against Main Protease of SARS-CoV-2 Through a Molecular Docking Study.

Author: MondalMilon, SarkarChandan, JamaddarSarmin, KhaliphaAbul B R, IslamMuhammad Torequl, MahafzahAzmi, MubarakMohammad S

COVID-19 treatment

This article discusses the global COVID-19 pandemic and the need for antiviral treatments. It highlights the main viral protease as a potential target for antiviral agents due to its crucial role in viral replication.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

The economic and public health impact of intellectual property licensing of medicines for low-income and middle-income countries: a modelling study.

Author: MorinSébastien, MoakHannah Barron, Bubb-HumfryesOliver, von DrehleChristian, LazarusJeffrey V, BurroneEsteban

HIV/HCV treatment access

This study aimed to investigate the economic and health effects of voluntary licensing for medicines for HIV and hepatitis C virus (HCV) in low-income and middle-income countries (LMICs).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Effects of a Fixed-Dose Co-Formulation of Daclatasvir, Asunaprevir, and Beclabuvir on the Pharmacokinetics of a Cocktail of Cytochrome P450 and Drug Transporter Substrates in Healthy Subjects.

Author: GarimellaTushar, TaoXiaolu, SimsKaren, ChangYi-Ting, RanaJignasa, MyersElsa, Wind-RotoloMegan, BhatnagarRahul, EleyTimothy, LaCretaFrank, AbuTarifMalaz

Drug interactions

Daclatasvir/asunaprevir/beclabuvir does not affect CYP1A2, CYP2C8, or CYP2C9, but may interact with CYP3A4, CYP2D6, and OATP substrates. Co-administration with agents solely metabolized by CYP2C19 is not recommended.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

25.

Seroprevalence, Genotyping, and Monitoring of Hepatitis C Viral Loads in Patients on Antivirals in Burkina Faso.

Author: YelemkoureEdwige T, YonliAlbert T, SombieHermann K, TaoIssoufou, ZouréAbdou Azaque, OuattaraAbdoul Karim, SorghoAbel P, ZongoArsène W, ZebaMoctar T A, KiendrebeogoIsabelle T, BadoProsper, KabréMadeleine K, ZohonconThéodora M, DjigmaFlorencia W, Obiri-YeboahDorcas, SimporeJacques

HCV treatment

This study investigated the seroprevalence of hepatitis C virus (HCV) infection, characterized circulating genotypes, and monitored HCV viral loads in patients receiving antiviral treatment in Burkina Faso. The findings contribute to understanding the burden of HCV infection and guiding treatment strategies in this specific region.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

26.

Is Daclatasvir a suitable substitute for Amphotericin B in the treatment of Mucormycosis when Amphotericin B is scarce?

Author: ThangarajuPugazhenthan, Tanguturi YellaSree Sudha, Arumugam RamamurthyVijayakumar, MuthusamySivakumar, Mohamed Thameemul AnsariLappathai Habib, NavabshanIrfan, VenkatesanSajitha

Drug development

This abstract discusses the use of molecular docking as a tool for investigating potential drug treatments for mucormycosis, a serious fungal infection. The abstract highlights the potential of molecular docking to simulate the interaction of potential drugs with membrane proteins, providing insights into the mechanism of action and potential efficacy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

27.

[Comparative evaluation of the effectiveness of narlaprevir in the composition of interferon and interferon-free treatment regimens for patients with chronic hepatitis C].

Author: GrushkoI P, RomanovaE B, TverdokhlebovaT I, GaponM N, VodyanitskayaS Y

Favorable safety profile
High virological response
None

Narlaprevir in the non-interferon mode showed similar efficacy to interferon-containing treatment regimen in patients with chronic hepatitis C (CHC) genotype 1b, with a sustained virological response achieved in 90% of patients. The non-interferon mode also demonstrated a more favorable safety profile.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Russian

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