Including cirrhosisRibavirinInfectionPolymorphismsInterleukinNear the IL28B geneRs12979860SVR12Chronic hepatitis C virHepatitis C genotypeHeterozygous genotypeGeneAntiviralVirologicalMulticenter studySNPsViral loadSpontaneous clearanceSubtypesResponseLiverGrazoprevirSubgroupAntibodyRelapseRegimensVariantsSofosbuvirAntiviralsMutationsGeneticVirusCombinationTherapyHealthySuccessfullyStudyResponses
Including cirrhosis1
- LONDON (April 12, 2014) -- Janssen R&D Ireland (Janssen) today announced positive new data from the clinical development program of the protease inhibitor simeprevir, including final data from cohort 2 of the Phase 2 COSMOS study of simeprevir administered once daily with Gilead Sciences, Inc.'s nucleotide inhibitor sofosbuvir, with and without ribavirin, in adult patients chronically infected with genotype 1 hepatitis C virus (HCV) and advanced fibrosis, including cirrhosis. (jnj.com)
Ribavirin24
- Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. (uni-koeln.de)
- Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-alpha and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. (uni-koeln.de)
- The addition of ribavirin did not improve SVR rates and consistent responses for both treatment arms were seen across HCV genotype subgroups after 12 weeks. (jnj.com)
- In genotype 1a patients with the Q80K polymorphism at baseline, 89 percent and 83 percent achieved SVR12 after 12 weeks of treatment with and without ribavirin, respectively. (jnj.com)
- DAKLINZA is indicated for use with sofosbuvir, with or without ribavirin, for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 or genotype 3 infection [see DOSAGE AND ADMINISTRATION and Clinical Studies ]. (rxlist.com)
- Consider screening for the presence of NS5A polymorphisms at amino acid positions M28, Q30, L31, and Y93 in patients with cirrhosis who are infected with HCV genotype 1a prior to the initiation of treatment with DAKLINZA and sofosbuvir with or without ribavirin [see Microbiology , Table 11]. (rxlist.com)
- The optimal duration of DAKLINZA and sofosbuvir with or without ribavirin has not been established for HCV genotype 3 patients with cirrhosis or for HCV genotype 1 patients with Child-Pugh C cirrhosis [see Clinical Studies ]. (rxlist.com)
- The current standard of care for HCV, pegylated interferon combined with ribavirin, causes serious side effects and only cures 40 to 50 percent of genotype 1 patients. (natap.org)
- For previously treated patients with HCV genotype 1 infection, no data exists with the combination of Sovaldi, ribavirin and peginterferon alfa (see section 4.4). (medicines.org.uk)
- especially for those subgroups who have one or more factors historically associated with lower response rates to interferon-based therapies (e.g. advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non CC genotype, prior null response to peginterferon alfa and ribavirin therapy). (medicines.org.uk)
- Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients with chronic HCV genotype 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. (who.int)
- How will the magnitudes of the health impacts measured in Question #2 change if IL-28B patient genotyping is used to offer triple therapy to those less likely to benefit from two-drug pegylated interferon + ribavirin? (va.gov)
- ABSTRACT Single nucleotide polymorphisms (SNPs) in the Interleukin (IL)-28B gene, namely rs12979860, could predict response to pegylated interferon--ribavirin (PR) therapy in hepatitis C virus genotype 1 (HCV-1)-infected patients. (who.int)
- In conclusion, sustained virological response in genotype 4 Egyptian patients treated with PEG-IFN alfa-2a and ribavirin was estimated around 60%, intermediate between sustained virological response observed in genotype 1 and genotype 2-3 patients in Western countries. (citationimpact.com)
- NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. (pasteur.fr)
- Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90-96) in prior non-responders infected with HCV genotype 1. (pasteur.fr)
- Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. (pasteur.fr)
- Another 129 people with genotype 1a or 1b where assigned to take grazoprevir plus either 20 mg or 50 mg elbasvir plus ribavirin, or else 50 mg elbasvir without ribavirin, for 12 weeks. (hivandhepatitis.com)
- for genotype 1b patients, the SVR12 rates were reversed: 95% with grazoprevir plus elbasvir alone and 92% with ribavirin added. (hivandhepatitis.com)
- Prior treatment response to PEG-IFNα/ribavirin and IL28B genotype was independently associated with SVR12 in both groups. (elsevierpure.com)
- The backbone of treatment for chronic hepatitis C virus (HCV) infection regardless of genotype was combination therapy with injectable pegylated interferon-alfa (PEG-IFNa) plus oral ribavirin. (medscape.com)
- The direct-acting antiviral agents (DAAs), first introduced in 2011, offered enhanced efficacy when combined with both PEG-IFN and ribavirin, particularly for genotype 1 infections. (medscape.com)
- It is indicated for the treatment of chronic hepatitis C genotypes 1 and 4 infection in combination with peginterferon alfa and ribavirin. (medscape.com)
- Depending on the genotype and other variables (eg, presence of cirrhosis, post liver transplantation), the regimen may also include ribavirin. (medscape.com)
Infection13
- Shin, JI & Eisenhut, M 2013, ' MiR-122, IL28B genotype and the response to interferon in chronic hepatitis C virus infection ', Nature Reviews Immunology , vol. 13, no. 12, pp. 902. (elsevierpure.com)
- Prior infection with HCV does not protect against later infection with the same or different genotypes of the virus. (cdc.gov)
- 2014) The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection Hepatology 59:(1). (wikipedia.org)
- Of fifty-three patients with genotype 1 infection included in this examination, IL28B SNPs at rs8099917, evolving numbers of ISDR on NS5A (aa2209-aa2248) and core protein transformation at aa70 or aa91 were discdone withd. (ika.ie)
- In the last years, single nucleotide polymorphisms (SNPs) upstream IL28-B gene have been related to treatment-induced clearance of HCV infection caused by genotype 1 HCV. (unifi.it)
- People with CC genotype are more likely to spontaneously clear acute infection or (during chronic infection) respond well to interferon-based treatment. (infohep.org)
- They therefore analysed the outcomes of 255 patients with hepatitis C genotype-1 infection. (infohep.org)
- On October 10, 2014, the US Food and Drug Administration (FDA) approved Harvoni™, a combination of ledipasvir, an NS5A inhibitor, and sofosbuvir, a polymerase inhibitor, to treat patients with chronic hepatitis C virus (HCV) infection, genotype 1. (hemaware.org)
- The IL28B non-CC variant has been associated with non-response to the IFN therapy and with lower rates of spontaneous clearance of HCV infection. (biomedcentral.com)
- This result indicates that the TT genotype may be more effective in the progression of HCV infection than other genotypes. (balkanmedicaljournal.org)
- It is indicated for the treatment of CHC infection genotypes 1, 2, 3, and 4 as part of a combination antiviral regimen, including those with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation) to prevent HCV recurrence and those with HCV/HIV-1 coinfection. (medscape.com)
- It is indicated for use with sofosbuvir for chronic HCV genotypes 1 and 3 infection. (medscape.com)
- The oral combination is indicated for treatment of adults with chronic hepatitis C infection with genotype 1, 4, 5, or 6. (medscape.com)
Polymorphisms5
- The Interleukin 28B (IL28B) rs12979860 polymorphisms was recently reported to be associated with the human T-cell leukemia virus type 1 ( HTLV-1 ) proviral load (PvL) and the development of the HTLV-1-associated myelopathy / tropical spastic paraparesis (HAM/TSP). (bvsalud.org)
- Our study failed to support the previously reported positive association between the IL28B rs12979860 polymorphisms and an increased risk of developing HAM/TSP in the Brazilian population . (bvsalud.org)
- and having certain host genetic polymorphisms, most notably those near the IL28B gene ( 6 , 7 ). (cdc.gov)
- Interleukin-28B (IL28B) single nucleotide polymorphisms may play an important role in the clearance of HCV spontaneously or with treatment. (balkanmedicaljournal.org)
- IL28B polymorphisms were genotyped by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) in all subjects. (balkanmedicaljournal.org)
Interleukin2
- The discovery of a genetic polymorphism in the interleukin 28B (IL28B) region on chromosome 19 of HCV patients depicted a more complex virus-host interaction. (biomedcentral.com)
- Notably, sex had a major impact on antiviral responses in concert with IL28B (interleukin 28B)/IFNL4 genotype, with stronger interferon and humoral responses in females. (ox.ac.uk)
Near the IL28B gene1
- Although all of the identified variants in the three studies lie in or near the IL28B gene, none of them has an obvious effect on the function of this gene, which encodes interferon-3, a growth factor with similarities to the interferon- preparations used as treatment. (blogspot.com)
Rs129798603
- Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load. (bvsalud.org)
- RÉSUMÉ Les polymorphismes mononucléotidiques du gène de l' Interleukine (IL)-28B , en l'occurence le rs12979860, permettent de prédire la réponse au traitement par interféron- pégylé associé à la ribavirine chez des patients infectés par le virus de l'hépatite C de génotype 1. (who.int)
- A significant increase was observed in the frequencies of IL28B rs12979860 TT genotypes in the CHC patients (20.6%) compared to the healthy control group (8.7%) (p=0.033). (balkanmedicaljournal.org)
SVR123
- Final results from cohort 2 of the Phase 2 COSMOS study demonstrated that 93 percent of patients with genotype 1 HCV and advanced liver fibrosis (METAVIR scores F3 and F4) who were treated with simeprevir and sofosbuvir for 12 weeks achieved sustained virologic response 12 weeks after the end of treatment (SVR12). (jnj.com)
- Sustained virologic response (SVR12) rates are reduced in HCV genotype 3-infected patients with cirrhosis receiving DAKLINZA in combination with sofosbuvir for 12 weeks [see Clinical Studies ]. (rxlist.com)
- The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients. (pasteur.fr)
Chronic hepatitis C vir1
- The US Food and Drug Administration (FDA) approved the combination of Janssen's Olysio™(simeprevir) and Gilead's Sovaldi® (sofosbuvir) to treat patients with chronic hepatitis C virus, genotype 1. (hemaware.org)
Hepatitis C genotype1
- These can also be affected by hepatitis C genotype and patient characteristics. (infohep.org)
Heterozygous genotype2
- The homozygous C allele genotype (CC) was associated with sustained viral response (SVR) to therapy compared with the homozygous T allele genotype (TT) and the heterozygous genotype (CT). (who.int)
- A total of 24.7% has a heterozygous genotype, showing one IL28-B SNP (18.6% rs12979860CT/rs8099917TT genotype, 6.1% rs12979860TT/rs8099917TG genotype). (unifi.it)
Gene4
- Presence of the IL28B gene has been associated with improved treatment responses , so patients were tested for its presence and analysis was conducted to see if it affected response rates. (infohep.org)
- The presence of the IL28B gene did not affect treatment response rates in patients whose viral load was below the TMA assay limit of detection. (infohep.org)
- Three-quarters had harder-to-treat HCV genotype 1a and most had unfavorable IL28B gene variants. (hivandhepatitis.com)
- T) gene polymorphism frequency of the TT genotype and T allele was higher than in healthy control subjects. (balkanmedicaljournal.org)
Antiviral3
- Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients. (uni-koeln.de)
- There is great potential to improve health outcomes for Veterans and other patients with chronic genotype 1 (GT1) Hepatitis C (HCV) infections through the use of newly-available directly acting antiviral (DAA) medications and patient genotyping (IL-28B). (va.gov)
- IL28B can regulate the immune response of cells and promote the occurrence of insulin-dependent cytotoxicity mediated by NK cells, thus playing an antiviral role. (creativebiomart.net)
Virological3
- We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. (hindawi.com)
- Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor ( P = 7.38 × 10 −4 ). (hindawi.com)
- This treatment provides rates of sustained virological response (SVR, undetectable serum levels of HCV RNA at least 6 months after completion of therapy) of 40-50% among patients with HCV genotype 1 (G1) who have not received previous treatment (treatment-naïve patients) [ 1 - 3 ]. (hindawi.com)
Multicenter study1
- Methods: This multicenter study consisted of 835 consecutive Japanese HCV genotype 1b patients treated in a clinical setting, 716 of whom were enrolled (simeprevir=256 and telaprevir=460). (elsevierpure.com)
SNPs2
- Only 19.8% of patients shows the IL28-B wildtype genotype (rs12979860CC/rs8099917TT), while the 1.2% carries both SNPs in homozygous status (rs12979860TT/rs8099917GG genotype). (unifi.it)
- The four GWAS studies found the same cluster of SNPs around IL28B, nicely cross-validating the studies. (blogspot.com)
Viral load2
- There was no correlation between SVR patients' genotypes and early response to therapy or HCV baseline viral load. (who.int)
- These should include a consideration of "all available parameters such as baseline viral load, early viral kinetics, IL28B genotype, and histological staging. (infohep.org)
Spontaneous clearance1
- Not only do patients with the "high expression" genotype respond better to therapy, but this genotype also predicts spontaneous clearance of the virus. (blogspot.com)
Subtypes2
- Seven HCV genotypes and 67 subtypes have been identified ( 9 ). (cdc.gov)
- We found that the mPTP species delimitation tool identified even without adapting its default parameters taxonomic clusters that either correspond to the currently acknowledged genotypes or to known subdivision of genotypes (subtypes or subgenotypes). (peerj.com)
Response3
- The study also evaluated in a retrospective way patient's treatment response in correlation with IL28-B genotype and clinical disease stage. (unifi.it)
- Of course, I could respond with the boilerplate response (found in at least one of the papers) that patients with the "poor response" genotype. (blogspot.com)
- After Part A saw good outcomes for previously untreated genotype 1 hepatitis C patients without liver cirrhosis, the study was expanded to include more people with traditional predictors of poor treatment response. (hivandhepatitis.com)
Liver4
- The final data, along with an additional analysis from COSMOS cohort 1 and new subgroup analyses of Phase 3 data in genotype 1 and genotype 4 HCV patients, were presented at The International Liver Congress™ 2014 of the European Association for the Study of the Liver (EASL) in London. (jnj.com)
- the liver, but not with the HCV genotype. (cxcr-signal.com)
- IL28B will have a certain impact on the function of other organs of the body, such as the liver, kidneys, etc., but the use of normal doses in clinical practice is generally safe. (creativebiomart.net)
- There was no significant difference in liver fibrosis and liver necroinflammation distribution among the CC, CT and TT genotypes with mild, moderate and severe groups (p=0.058 and p=0.791, respectively). (balkanmedicaljournal.org)
Grazoprevir1
- Among the HCV monoinfected participants, a group of 30 people with genotype 1a received grazoprevir plus 50 mg elbasvir for 8 weeks. (hivandhepatitis.com)
Subgroup1
- The aim of our study was to evaluate the rate of IL28B genotypes in patients with Chronic Hepatitis-C (CHC) and healthy control subjects and to examine the characteristics of patients in each IL28B subgroup. (balkanmedicaljournal.org)
Antibody1
- The Virology study combines topics in areas such as Epitope, Antibody, Drug and Genotype. (research.com)
Relapse1
- Conclusions: Considering the effectiveness and safety, simeprevir-based triple therapy will continue to be a useful treatment option in Japan for treatment-naïve or prior relapse patients with a favorable IL28B genotype. (elsevierpure.com)
Regimens1
- Table 1 provides the recommended DAKLINZA-containing treatment regimens and duration based on HCV genotype and patient population. (rxlist.com)
Variants1
- These six genotypes are stable, heritable variants that differ in their geographic distribution. (biomedcentral.com)
Sofosbuvir2
- Daklinza (daclatasvir) is a hepatitis C virus (HCV) NS5A inhibitor indicated for use with sofosbuvir for the treatment of chronic HCV genotype 3. (rxlist.com)
- For genotype 1a, it may be prescribed as an all-oral regimen in combination with sofosbuvir. (medscape.com)
Antivirals2
- What are the current usage patterns of directly acting antivirals and of IL-28B patient genotyping in the VA health system? (va.gov)
- The particular combination of antivirals is determined by genotype. (medscape.com)
Mutations1
- Neither the homozygote TT nor the heterozygote CT mutations nor the combination genotypes (TT/CT) were associated with a greater PvL. (bvsalud.org)
Genetic1
- This variety can be caused by disease-related factors (for example, viral genotype) or host-factors (genetic/epigenetic). (biomedcentral.com)
Virus3
- The overlap of predicted clusters with taxonomically acknowledged genotypes implies that virus classification can be successfully automated. (peerj.com)
- For hepatitis C virus (HCV) genotype specific activity, see sections 4.4 and 5.1. (medicines.org.uk)
- 4 comparés à 22 sujets ayant connu une clairance spontanée du virus de l'hépatite C et à 70 volontaires en bonne santé. (who.int)
Combination1
- Therefore, the combination of IL28B with other drugs can improve the efficacy. (creativebiomart.net)
Therapy5
- IL-28B genotyping can help to identify patients least likely to respond to standard therapy and hence who stand to benefit the most from triple therapy and for whom, therefore, the increased risks of side-effects may be most justified. (va.gov)
- Our findings describe how IL-28B SNP genotyping may guide appropriate selection of HCV-4-infected patients for PR therapy. (who.int)
- IL28A & IL28B loci produce proteins classified as interferons and it is another interferon (alpha) which is a key part of the standard therapy. (blogspot.com)
- 25 IU/mL [detectable/undetectable in IL28B CC patients or undetectable in IL28B CT/TT patients] at Week 2 and undetectable at Weeks 4 and 8) were eligible to stop all treatment at the end of Week 12, otherwise PR therapy was continued to Week 24. (gencat.cat)
- In a study of treatment-naïve US veterans with genotype 1 HCV, ombitasvir-based therapy was considered to be the most economically efficient strategy. (medscape.com)
Healthy1
- Maria Prins combines subjects such as Healthy subjects and Genotype with her study of Virology. (research.com)
Successfully1
- All 112 samples were successfully genotyped and their PvLs compared. (bvsalud.org)
Study1
- IL28B has achieved remarkable results in the treatment of hepatitis C. The study found that patients with a specific genotype, which is related to IL28B, were better able to benefit from treatment with the hepatitis drug interferon. (creativebiomart.net)