Effects of simeprevir: A Synthesis of Findings from 29 Studies

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Original Abstract of the Article

Major Research Findings

Simeprevir, a drug used to treat hepatitis C, has shown various effects in different studies. 3 found that simeprevir exhibited genotoxic effects in HepG2 cells, a human-derived liver cell line, while sofosbuvir did not. Simeprevir, at high concentrations, inhibited nuclear division and increased the frequency of micronuclei, indicating potential damage to chromosomes. Additionally, 13 reported that certain mutations in the NS3 gene of HCV (resistance-associated substitutions or RAS) can impair the effectiveness of simeprevir, including other direct-acting antiviral agents (DAAs). This means that some patients with these mutations may not respond well to simeprevir treatment. On the other hand, 7 showed that simeprevir could be repurposed as a potential treatment for leishmaniasis, a parasitic disease. It was found to bind to a specific enzyme in the parasite, LdSMT, and inhibit its growth. Furthermore, 27 investigated simeprevir’s effect on SARS-CoV-2, the virus responsible for COVID-19. The study showed that simeprevir could inhibit SARS-CoV-2 replication in vitro, but it was not effective in vivo in a transgenic mouse model. This suggests that simeprevir may not be a suitable treatment option for COVID-19.

Benefits and Risks

Benefits Summary

Simeprevir has demonstrated efficacy in treating hepatitis C. Its potential for repurposing as a treatment for leishmaniasis has also been explored. Additionally, simeprevir has shown antiviral activity against SARS-CoV-2 in vitro.

Risks Summary

Simeprevir has shown potential genotoxicity in HepG2 cells, particularly at higher concentrations. The presence of certain mutations in the HCV NS3 gene (RAS) may compromise the effectiveness of simeprevir, leading to suboptimal treatment outcomes. It’s important to note that the effectiveness of simeprevir against SARS-CoV-2 in vivo is still unclear and requires further research.

Comparison Across Studies

Similarities

Multiple studies have consistently shown that simeprevir is effective in treating hepatitis C. The research also suggests that simeprevir may have potential applications beyond hepatitis C treatment, such as repurposing for leishmaniasis or even addressing other viral infections.

Differences

The research on simeprevir has highlighted diverse aspects, including its potential genotoxicity, impact on patients with specific HCV mutations, and potential efficacy against other pathogens, such as SARS-CoV-2. These differences can be attributed to varying research methodologies, study populations, drug concentrations, and administration methods.

Consistency and Contradictions in Findings

While numerous studies have established simeprevir’s effectiveness in treating hepatitis C, concerns remain regarding its potential genotoxicity and the impact of specific HCV mutations (RAS) on treatment outcomes. The findings regarding SARS-CoV-2 are particularly noteworthy, highlighting the need for further investigation to confirm simeprevir’s efficacy and determine appropriate dosage regimens for potential use in treating COVID-19. Further research is crucial to address these inconsistencies and develop a more comprehensive understanding of simeprevir’s effects.

Considerations for Real-World Applications

Simeprevir is widely used in treating hepatitis C, but its potential genotoxic effects and the impact of specific HCV mutations warrant careful consideration. Patients with these mutations may require alternative treatment strategies. Furthermore, while in vitro studies suggest potential for simeprevir in treating COVID-19, more research is needed to confirm its efficacy and safety in humans. Healthcare professionals should carefully evaluate each patient's individual circumstances, including their HCV genotype, before prescribing simeprevir.

Limitations of Current Research

Current research on simeprevir has several limitations. Long-term effects and safety data in humans are still limited. Further research is needed to delve deeper into the mechanisms behind simeprevir’s effects on RAS, SARS-CoV-2, and to explore its potential for repurposing for other diseases.

Future Research Directions

Future research should focus on addressing the limitations mentioned above. In particular, extensive studies on simeprevir’s long-term effects and safety in humans are crucial. Further investigation into the mechanisms behind its action against RAS and SARS-CoV-2, as well as its potential for repurposing for other diseases, is essential. Through rigorous research, a more comprehensive understanding of simeprevir’s effects can be achieved, leading to safer and more effective clinical applications.

Conclusion

Simeprevir remains a valuable treatment option for hepatitis C, but its potential genotoxic effects and the impact of specific HCV mutations require ongoing monitoring and investigation. Its potential for treating COVID-19 and other diseases needs further research to confirm its efficacy and safety. Healthcare professionals should carefully consider all aspects of simeprevir before prescribing it to ensure optimal patient care.

Literature analysis of 29 papers
Positive Content
25
Neutral Content
1
Negative Content
3
Article Type
2
0
1
1
29
1.

Efficacy and safety of sofosbuvir-based therapy in hepatitis C virus recurrence post living donor liver transplant: A real life egyptian experience.

Author: YosryAyman, Gamal EldeenHadeel, MedhatEman, MehrezMai, ZayedNaglaa, ElakelWafaa, AbdelmoniemReham, KaddahMona, AbdelazizAshraf, EsmatGamal, El-SerafyMagdy, DossWahid

HCV recurrence treatment

Sofosbuvir-based regimens are effective and safe for treating recurrent HCV post-liver transplantation.

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

Language : English

2.

Use of a Bile Salt Export Pump Knockdown Rat Susceptibility Model to Interrogate Mechanism of Drug-Induced Liver Toxicity.

Author: LiYutai, EversRaymond, HafeyMichael J, CheonKyeongmi, DuongHong, LynchDonna, LaFranco-ScheuchLisa, PacchioneStephen, TamburinoAlex M, TanisKeith Q, GeddesKristin, HolderDaniel, ZhangNanyan Rena, KangWen, GonzalezRaymond J, Galijatovic-IdrizbegovicAlema, PearsonKara M, LebronJose A, GlaabWarren E, SistareFrank D

Drug-induced liver injury

This study presents a novel rat model for assessing the hepatotoxicity of bile salt export pump (BSEP) inhibitors. The model uses siRNA knockdown of Bsep to enhance the hepatotoxicity of BSEP inhibitors, potentially improving the prediction of drug-induced liver injury in humans.

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

Language : English

4.

Comparative Real Life Egyptian Experience of the Combination of Sofosbuvir Plus Daclatasvir or Simeprevir for 12 Weeks in Naïve Cirrhotic Patients Infected with HCV Genotype 4.

Author: AhmedSayed, HassanEssam, GomaaAhmed, EsamatGamal, RamadanAhmed, AhmedManar, ElsayedAya, A WahshEngy

HCV cure

Chronic hepatitis C virus (HCV) infection is a major global health problem, with HCV-G4 being a significant threat in Egypt. This article discusses the use of new interferon-free regimens, specifically direct-acting antiviral oral tablets, for the cure of HCV.

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.

Language : English

5.

Natural prevalence of NS3 gene resistance-associated substitutions (RASs) in patients with chronic hepatitis C from the state of Pará/Brazil.

Author: da SilvaDesirée Lopes, NunesHeloisa Marceliano, FreitasPedro Eduardo Bonfim

Drug resistance

This study identified and established the natural prevalence of RASs in the NS3 gene in patients with chronic hepatitis C in the state of Pará, northern Brazil. The general natural prevalence of RASs in the NS3 gene was 37.5 % (Y56F and S122T).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy.

Author: KilengHege, KjellinMidori, AkaberiDario, BergforsAssar, DubergAnn-Sofi, WesslénLars, DanielssonAstrid, Gangsøy KristiansenMagnhild, GuttebergTore, GollRasmus, LannergårdAnders, LennerstrandJohan

HCV genotype 1a treatment
Treatment response impairment

This multi-center study investigated the effects of baseline NS3-RASs and clinically relevant NS5A-RASs in patients with HCV genotype 1a infection on treatment outcome.

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

7.

Repurposing of FDA-approved drugs as inhibitors of sterol C-24 methyltransferase of Leishmania donovani to fight against leishmaniasis.

Author: TabrezShams, RahmanFazlur, AliRahat, MuhammadFida, AlshehriBader Mohammed, AlaidarousMohammed A, BanawasSaeed, DukhyilAbdul Aziz Bin, RubAbdur

Antileishmanial

Simeprevir, an FDA-approved antiviral drug, exhibited significant binding affinity to LdSMT, a key enzyme in the sterol biosynthesis pathway of Leishmania donovani. Simeprevir effectively inhibited the growth of L. donovani promastigotes and induced ROS generation, suggesting its potential as an antileishmanial drug.

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

9.

JNJ-4178 (AL-335, Odalasvir, and Simeprevir) for 6 or 8 Weeks in Hepatitis C Virus-Infected Patients Without Cirrhosis: OMEGA-1.

Author: ZeuzemStefan, BourgeoisStefan, GreenbloomSusan, ButiMaria, AghemoAlessio, LamperticoPietro, JanczewskaEwa, LimSeng Gee, MorenoChristophe, BuggischPeter, TamEdward, CorbettChris, WillemsWouter, VijgenLeen, FeveryBart, Ouwerkerk-MahadevanSivi, AckaertOliver, BeumontMaria, KalmeijerRonald, SinhaRekha, BiermerMichael,

HCV infection treatment
Viral relapse

This study evaluated the efficacy and safety of a 6- or 8-week treatment regimen with three direct-acting antiviral agents (AL-335, odalasvir, and simeprevir) in patients with chronic hepatitis C virus (HCV) infection. The study found high sustained virologic response rates (98.9% and 97.8% after 6 and 8 weeks, respectively) with good tolerability, suggesting this regimen may be an effective and safe treatment option for HCV infection.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
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.
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

10.

Drug-Drug Interactions between Direct Oral Anticoagulants and Hepatitis C Direct-Acting Antiviral Agents: Looking for Evidence Through a Systematic Review.

Author: BellesiniMarta, BianchinMatteo, CorradiChiara, DonadiniMarco Paolo, RaschiEmanuel, SquizzatoAlessandro

Bleeding risk

This systematic review examined drug-drug interactions (DDIs) between direct oral anticoagulants (DOACs) and hepatitis C direct-acting antiviral agents (DAAs). The authors highlight the potential for DAAs to increase DOAC exposure and bleeding risk.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

12.

Tolerability of Erythrocyte Ribavirin Triphosphate Concentrations Depends on the ITPA Genotype.

Author: TanakaYoichi, InoueAkiko, MizunumaTomohiko, MatsumuraHaruka, YokomoriHiroaki, KomiyamaTakako, OtoriKatsuya

Hepatitis C treatment
Hemolytic anemia

This study evaluated the time-dependent association of ribavirin triphosphate concentrations in erythrocytes, ribavirin-induced toxicity, and virological response to ribavirin treatment for hepatitis C.

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

Language : English

13.

Baseline resistance associated substitutions in HCV genotype 1 infected cohort treated with Simeprevir, Daclatasvir and Sofosbuvir in Brazil.

Author: AguiarBruna Forte, CamposGuilherme Rodrigues Fernandes, RodriguesJoão Paulo Vilela, MarquesNayara Nathie, MolinaBárbara Floriano, BittarCintia, SouzaFernanda Fernandes, MartinelliAna de Lourdes Candolo, RahalPaula, PereiraLeonardo Régis Leira

HCV treatment
Viral resistance

Direct-acting antivirals (DAAs) are effective for the treatment of chronic hepatitis C, but viral resistance mutations can lead to treatment failure.

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

Language : English

14.

Extrahepatic Malignancies After Treatment with Direct Antiviral Agents for Chronic HCV Infection.

Author: KhouryJohad, NassarGeorge, KramskyRimma, SaadiTarek

HCV clearance
Increased malignancy risk

A possible relationship between the use of direct-acting antiviral agents (DAAs) for chronic hepatitis C virus (HCV) infection and the development of extrahepatic malignancies was observed. Nine patients (2.08%) were diagnosed with malignancies after treatment, including lymphoma, laryngeal carcinoma, pancreatic adenocarcinoma, cervix carcinoma, lung carcinoma, transitional cell carcinoma of the urinary bladder, and metastatic breast cancer. The incidence of these malignancies in the cohort was higher than the general population.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

HCV genotype 1-6 NS3 residue 80 substitutions impact protease inhibitor activity and promote viral escape.

Author: PhamLong V, JensenSanne Brun, FahnøeUlrik, PedersenMartin Schou, TangQi, GhanemLubna, RamirezSantseharay, HumesDaryl, SerreStéphanie B N, SchønningKristian, BukhJens, GottweinJudith M

HCV treatment
PI resistance

This study investigated the effects of position-80-substitutions on fitness and PI-resistance for HCV genotypes 1-6.

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

17.

IFNL4 polymorphism effects on outcome of simeprevir, peginterferon, and ribavirin therapy for older patients with genotype 1 chronic hepatitis C.

Author: MoriNami, ImamuraMichio, KawakamiYoshiiku, NagaokiYuko, KawaokaTomokazu, TsugeMasataka, HiramatsuAkira, HayesC Nelson, AikataHiroshi, MikiDaiki, OchiHidenori, HondaYohji, TakakiShintaro, TsujiKeiji, ChayamaKazuaki,

This study investigated the efficacy of simeprevir plus pegylated-IFN and ribavirin therapy in older patients with chronic hepatitis C and the predictive value of the IFNL4 gene on treatment response.

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

Language : English

18.

Antiviral effects of simeprevir on multiple viruses.

Author: LiZheng, YaoFujia, XueGuang, XuYongfen, NiuJunling, CuiMengmeng, WangHongbin, WuShuxian, LuAiling, ZhongJin, MengGuangxun

Viral infection treatment

Simeprevir, a drug targeting the NS3/4A protease of hepatitis C virus (HCV), has been found to promote the transcription of IFN-β and ISG15, inhibiting the infection of host cells by multiple viruses including Zika virus, Enterovirus A71, and herpes simplex virus type 1. This suggests a broader antiviral potential for Simeprevir beyond HCV.

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

20.

Effectiveness and safety of simeprevir-based regimens for hepatitis C in Italy: The STIly observational study.

Author: GaetaGiovanni Battista, AghemoAlessio, MenzaghiBarbara, D'OffiziGianpiero, GiorginiAlessia, HassonHamid, BrancaccioGiuseppina, PalmaMaria, TerminiRoberta,

Hepatitis C treatment
SVR12
Adverse events

Simeprevir (SMV)-based regimens, including SMV/SOF and SMV/SOF+ribavirin (RBV), achieved a high sustained virologic response (SVR) rate in Italian patients with hepatitis C virus (HCV) genotypes 1 and 4. SVR12 was achieved by 94.2% of patients receiving SMV/SOF±RBV.

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.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : English

21.

Hepatitis C treatment with all-oral direct-acting antivirals: Effectiveness and tolerance in a multicenter, prospective, observational study from French general hospitals (APROVVIE, ANGH).

Author: ParienteAlexandre, ArpurtJean-Pierre, RémyAndré-Jean, Rosa-HézodeIsabelle, CausseXavier, HeluwaertFrédéric, MacaigneGilles, HenrionJean, RenouChristophe, SchneeMatthieu, SalloumHatem, HommelSéverine, PiletteChristophe, ArotcarenaRamuntxo, BarjonetGeorges, LisonHortensia, BourhisFrançois, JouannaudVincent, PauwelsArnaud, Le eaBricquirYann, GeageaEdmond, CondatBertrand, RipaultMarie-Pierre, ZanditenasDavid, de Montigny-LenhardtStéphanie, LabadieHélène, TissotBertrand, MaringeEric, CadranelJean-François, HagègeHervé, LesgourguesBruno,

Chronic hepatitis C treatment
Chronic hepatitis C

Various combinations of second-generation direct-acting antiviral agents (DAAs) were highly effective and well-tolerated in the treatment of chronic hepatitis C (CHC) patients in French hospitals.

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.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : English

22.

Drug repurposing using computational methods to identify therapeutic options for COVID-19.

Author: MahdianSoodeh, Ebrahim-HabibiAzadeh, ZarrabiMahboobeh

COVID-19 treatment

This study aimed to identify therapeutic options for COVID-19 using drug repurposing and virtual screening. Five proteins of COVID-19 were selected as target proteins for drug repositioning.

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

Language : English

23.

Direct-Acting Antivirals for Hepatitis C: Predictors of Early Discontinuation in the Real World.

Author: de Ávila MachadoMarina Amaral, de MouraCristiano Soares, KleinMarina, WinthropKevin, CarletonBruce, AbrahamowiczMichal, FeldJordan, CurtisJeffrey R, BeauchampMarie-Eve, BernatskySasha

Low discontinuation rate
Early discontinuation

Second-generation direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection had low rates of early discontinuation, averaging 4.2% across six drug regimens. While women, patients with baseline anemia, and those on Medicare or Medicaid were more likely to discontinue treatment, the overall low rates suggest the effectiveness of these therapies.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

24.

The pharmacological interactions between direct-acting antivirals for the treatment of chronic hepatitis c and psychotropic drugs.

Author: RonceroCarlos, VillegasJose Luis, Martínez-RebollarMaria, ButiMaria

Hepatitis C treatment

Direct-acting antivirals (DAAs) for hepatitis C and psychotropic medications are frequently co-administered, but interactions between them are not well-understood. This review focuses on potential drug-drug interactions between approved DAA regimens and commonly used psychoactive substances.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

26.

A comparative study of the efficiency of HCV NS3/4A protease drugs against different HCV genotypes using in silico approaches.

Author: EzatAhmed A, ElshemeyWael M

Effective treatment
Drug resistance

This study suggests that Direct Acting Antivirals (DAAs) are not equally effective against all Hepatitis C Virus (HCV) genotypes. The study found that simeprevir was the most effective drug overall, while P2-P4 macrocyclic drugs showed better performance against genotypes 2, 3, and 5.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

28.

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

29.

No difference between direct-acting antivirals for hepatitis C in hepatocellular carcinoma risk.

Author: MunElijah J, GreenPamela, BerryKristin, IoannouGeorge N

There were no significant differences in the risk of hepatocellular carcinoma (HCC) after antiviral treatment with different direct-acting antivirals (DAAs) for hepatitis C virus, suggesting that DAAs do not have direct carcinogenic effects.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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