abt-450 and ledipasvir

abt-450 has been researched along with ledipasvir* in 14 studies

Reviews

5 review(s) available for abt-450 and ledipasvir

ArticleYear
The efficacy and safety of direct-acting antiviral regimens for end-stage renal disease patients with HCV infection: a systematic review and network meta-analysis.
    Frontiers in public health, 2023, Volume: 11

    Hepatitis C virus (HCV) infection is an independent risk factor associated with adverse outcomes in patients with end-stage renal disease (ESRD). Due to the wide variety of direct-acting antiviral regimens (DAAs) and the factor of renal insufficiency, careless selection of anti-hepatitis C treatment can lead to treatment failure and safety problems. The integrated evidence for optimized therapies for these patients is lacking. This study would conduct comparisons of different DAAs and facilitate clinical decision-making.. We conducted a systematic literature search in multiple databases (PubMed, Ovid, Embase, Cochrane Library, and Web of Science) up to 7 August 2023. Study data that contained patient characteristics, study design, treatment regimens, intention-to-treat sustained virologic response (SVR), and adverse event (AE) data per regimen were extracted into a structured electronic database and analyzed. The network meta-analysis of the estimation was performed by the Bayesian Markov Chain Monte Carlo methods.. Our search identified 5,278 articles; removing the studies with duplicates and ineligible criteria, a total of 62 studies (comprising 4,554 patients) were included. Overall, the analyses contained more than 2,489 male individuals, at least 202 patients with cirrhosis, and no less than 2,377 patients under hemodialysis. Network meta-analyses of the DAAs found that receiving ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (R) plus dasabuvir (DSV), glecaprevir (G)/pibrentasvir (P), and sofosbuvir (SOF)/ledipasvir (LDV) ranked as the top three efficacy factors for the HCV-infected ESRD patients. Stratified by genotype, the G/P would prioritize genotype 1 and 2 patients with 98.9%-100% SVR, the SOF/DCV regimen had the greatest SVR rates (98.7%; 95% CI, 93.0%-100.0%) in genotype 3, and the OBV/PTV/R regimen was the best choice for genotype 4, with the highest SVR of 98.1% (95% CI, 94.4%-99.9%). In the pan-genotypic DAAs comparison, the G/P regimen showed the best pooled SVR of 99.4% (95% CI, 98.6%-100%). DAA regimens without Ribavirin or SOF showed the lowest rates of AEs (49.9%; 95% CI, 38.4%-61.5%) in HCV-infected ESRD patients.. The G/P could be recommended as the best option for the treatment of pan-genotypic HCV-infected ESRD patients. The OBV/PTV/R plus DSV, SOF/Velpatasvir (VEL), SOF/Ledipasvir (LDV), and SOF/DCV would be reliable alternatives for HCV treatment with comparable efficacy and safety profiles.. https://www.crd.york.ac.uk/prospero/#searchadvanced, PROSPERO: CRD42021242359.

    Topics: Antiviral Agents; Bayes Theorem; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; Male; Network Meta-Analysis; Ritonavir; Treatment Outcome

2023
Sustained Virological Response in Special Populations with Chronic Hepatitis C Using Interferon-Free Treatments: A Systematic Review and Meta-analysis of Observational Cohort Studies.
    Clinical drug investigation, 2018, Volume: 38, Issue:5

    Hepatitis C treatment has changed considerably in recent years, and many interferon (IFN)-free therapies are now available. Considering the high rates of sustained virological response (SVR) presented by clinical trials for these treatments, high rates of effectiveness are also expected in real-world clinical practice. Hence, this study aimed to conduct a systematic review and meta-analysis of observational cohort studies to evaluate the clinical effectiveness and safety of IFN-free therapies for hepatitis C.. The search was performed in four electronic databases and included cohort studies that evaluated IFN-free schemes and provided data on SVR at 12 weeks after the end of treatment (SVR12) as the primary outcome. Overall and subgroup meta-analyses of patients' clinical conditions (e.g. co-infection with human immunodeficiency virus (HIV), cirrhosis, liver transplant, specific genotypes, and other conditions) were performed.. Sixty-eight studies encompassing a total of 24,151 patients were included for quantitative and qualitative analyses, evaluating six treatments: sofosbuvir with ledipasvir, daclatasvir, or simeprevir; daclatasvir with asunaprevir; paritaprevir/ritonavir in combination with ombitasvir and dasabuvir; and sofosbuvir with ribavirin. The overall analysis showed SVR rates of 88-96% for all treatments except sofosbuvir combined with ribavirin, which had SVR rates of approximately 80%. The results of subgroup analyses showed that the genotype 3 virus appears to be the most difficult to treat.. In order to choose the best treatment option, it is necessary to consider the patients' conditions and characteristics. In conclusion, the use of IFN-free therapies meets the high expectations created by clinical trials, including patients in special clinical conditions.

    Topics: 2-Naphthylamine; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Cohort Studies; Cyclopropanes; Drug Therapy, Combination; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Humans; Interferons; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Ribavirin; Ritonavir; Simeprevir; Sofosbuvir; Sulfonamides; Sustained Virologic Response; Treatment Outcome; Uracil; Valine

2018
Ideal oral combinations to eradicate HCV: The role of ribavirin.
    Journal of hepatology, 2016, Volume: 64, Issue:1

    Current all-oral interferon-free regimens offer sustained virological response (SVR) rates above 90% as well as 12-week treatment durations for the majority of patients with chronic hepatitis C virus (HCV), including treatment-naïve and -experienced patients with or without cirrhosis. There are multiple direct-acting antiviral (DAA) combinations that can be selected to optimize efficacy and safety outcomes. Each of them can be tailored according to different parameters including the use of ribarivin (RBV). For sofosbuvir (SOF)-based combinations, RBV is useful in the following situations: HCV genotype 1, treatment-experienced, cirrhotic patients, or patients with decompensated cirrhosis, and HCV genotype 3, cirrhotic patients. In these situations the addition of RBV allows to shorten the treatment to 12weeks in the majority of cases and therefore decreases the cost of the treatment. The need of RBV remains to be determined in cirrhotic patients with a SOF plus simeprevir regimen. RBV-containing regimens are recommended in all HCV genotype 1a patients who receive the 3-DAA combination: paritaprevir/r, ombitasvir, dasabuvir. Globally, the addition of RBV to the different combinations of DAA increases slightly the risk of anaemia. However severe anaemia was rare and easily manageable with RBV dose reduction without any impact on SVR. In practice, because RBV is cheap and well tolerated when combined with interferon-free regimen, it remains a useful tool to fine tune anti-HCV treatment regimens and optimize their results.

    Topics: Antiviral Agents; Benzimidazoles; Carbamates; Cyclopropanes; Drug Therapy, Combination; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Lactams, Macrocyclic; Macrocyclic Compounds; Proline; Pyrrolidines; Ribavirin; Simeprevir; Sofosbuvir; Sulfonamides; Valine

2016
Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives.
    Liver international : official journal of the International Association for the Study of the Liver, 2016, Volume: 36 Suppl 1

    There has been a revolution in the treatment of chronic hepatitis C. Several oral regimens combining direct-acting antivirals (DAAs) from different families [NS5B nucleotide inhibitors, NS5B non-nucleoside inhibitors, NS5A replication complex inhibitors and NS3/4A protease inhibitors (PI)] have been developed. These regimens result in an increase in sustained virological response (SVR) rates to above 90% and reduce the duration of treatment to 12 weeks or less. As of 2016 several regimens will be approved with additive potencies, without cross-resistance and with a good safety profile. Remaining issues will include increasing screening and access to care so that HCV may become the first chronic viral infection eradicated worldwide. This review summarizes results obtained with oral DAA combinations that have been approved and/or have completed phase 3 clinical trials for HCV infection and discusses future perspectives.

    Topics: 2-Naphthylamine; Amides; Anilides; Antiviral Agents; Benzimidazoles; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Combination; Female; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 4 or More Rings; Humans; Imidazoles; Lactams, Macrocyclic; Macrocyclic Compounds; Proline; Protease Inhibitors; Quinoxalines; Sofosbuvir; Sulfonamides; Uracil; Valine; Viral Nonstructural Proteins

2016
[New era in the treatment of chronic hepatitis C - novel direct acting antivirals].
    Orvosi hetilap, 2015, May-24, Volume: 156, Issue:21

    Chronic hepatitis C, without treatment, can cause liver cirrhosis, liver failure and liver cancer. The availability of new oral direct acting antivirals, such as the protease inhibitors simeprevir, asunaprevir and paritaprevir, the NS5A inhibitors daclatasvir, ledipasvir, and ombitasvir, the polymerase inhibitors Sofosbuvir and dasabuvir have resulted an enormous progress in the treatment of chronic hepatitis C, leading to >90% sustained viral response rates. Even the hard-to-treat or previously treatment ineligible patients can be cured with the combination of these drugs. Furthermore the treatment duration is much shorter, and the side effects are minimal. Today, treatment of all hepatitis C virus infected patients is recommended, and the best choices are the interferon-free options. Eradication of hepatitis C virus has become realistic, however, appropriate screening programs are mandatory to achieve this goal.

    Topics: 2-Naphthylamine; Administration, Oral; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Clinical Trials as Topic; Cyclopropanes; Drug Therapy, Combination; Fluorenes; Hepacivirus; Hepatitis C, Chronic; Heterocyclic Compounds, 3-Ring; Humans; Imidazoles; Interferons; Isoquinolines; Lactams, Macrocyclic; Liver Neoplasms; Macrocyclic Compounds; Nucleic Acid Synthesis Inhibitors; Proline; Protease Inhibitors; Pyrrolidines; Simeprevir; Sofosbuvir; Sulfonamides; Uracil; Uridine Monophosphate; Valine; Viral Load; Viral Nonstructural Proteins; Virus Replication

2015

Trials

1 trial(s) available for abt-450 and ledipasvir

ArticleYear
Outcome and adverse events in patients with chronic hepatitis C treated with direct-acting antivirals: a clinical randomized study.
    European journal of gastroenterology & hepatology, 2018, Volume: 30, Issue:10

    New potent direct-acting antiviral (DAA) regimens against hepatitis C virus have been approved in recent years. However, information about the rate of adverse events (AEs) across different DAA regimens is limited. We aimed to evaluate differences in AEs and treatment efficacy in patients with chronic hepatitis C (CHC), genotype (GT) 1 or 3, randomized to two different treatment arms, correspondingly.. We randomly assigned 96 patients in a 1 : 1 ratio, to treatment for 12 weeks with either paritaprevir/ombitasvir/ritonavir/dasabuvir/ribavirin (RBV) or ledipasvir/sofosbuvir (SOF)/RBV if infected with GT1 (72 patients) or to daclatasvir/SOF/RBV for 12 weeks or SOF/RBV for 24 weeks, if infected with GT3 (24 patients). Data on AEs were collected throughout the entire study period.. A total of 70 (97%) patients with CHC with GT1 and 20 (83%) patients with GT3 achieved cure. The GT3 treatment arm was prematurely terminated, owing to change in national treatment guidelines. Thus, only AEs for GT1 patients are described. AEs occurred in 70 (97%) GT1 patients, and most common AEs were anemia (n=56/78%), fatigue (n=53/74%), and headache (n=33/46%). No difference was observed in relation to treatment group (P=1.0), anemia (P=1.0), or liver cirrhosis (P=0.53). In seven (11%) patients, AEs assessed by the investigator to be possibly related to the DAA regimen were still present 12 weeks after treatment.. We found no difference in AEs possibly related to the DAA regimen in patients with CHC, but surprisingly, AEs possibly related to the DAA regimen persisted in a significant number of patients after treatment. This finding can be of importance for clinicians in relation to patient information concerning AEs possibly related to DAA treatment.

    Topics: 2-Naphthylamine; Adult; Anemia; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Cyclopropanes; Drug Therapy, Combination; Fatigue; Female; Fluorenes; Genotype; Headache; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Ribavirin; Ritonavir; Sofosbuvir; Sulfonamides; Treatment Outcome; Uracil; Valine; Viral Load

2018

Other Studies

8 other study(ies) available for abt-450 and ledipasvir

ArticleYear
Repurposing nonnucleoside antivirals against SARS-CoV2 NSP12 (RNA dependent RNA polymerase): In silico-molecular insight.
    Biochemical and biophysical research communications, 2021, 09-24, Volume: 571

    The pandemic of SARS-CoV-2 has necessitated expedited research efforts towards finding potential antiviral targets and drug development measures. While new drug discovery is time consuming, drug repurposing has been a promising area for elaborate virtual screening and identification of existing FDA approved drugs that could possibly be used for targeting against functions of various proteins of SARS-CoV-2 virus. RNA dependent RNA polymerase (RdRp) is an important enzyme for the virus that mediates replication of the viral RNA. Inhibition of RdRp could inhibit viral RNA replication and thus new virus particle production. Here, we screened non-nucleoside antivirals and found three out of them to be strongest in binding to RdRp out of which two retained binding even using molecular dynamic simulations. We propose these two drugs as potential RdRp inhibitors which need further in-depth testing.

    Topics: Amides; Antiviral Agents; Benzimidazoles; Carbamates; Catalytic Domain; Computer Simulation; Coronavirus RNA-Dependent RNA Polymerase; COVID-19; COVID-19 Drug Treatment; Cyclopropanes; Drug Evaluation, Preclinical; Drug Repositioning; Fluorenes; Humans; Lactams, Macrocyclic; Molecular Docking Simulation; Molecular Dynamics Simulation; Pandemics; Proline; Protein Conformation; Quinoxalines; SARS-CoV-2; Sulfonamides

2021
Editorial: is sofosbuvir-based therapy suitable for patients with advanced chronic kidney disease?
    Alimentary pharmacology & therapeutics, 2018, Volume: 48, Issue:3

    Topics: 2-Naphthylamine; Anilides; Benzimidazoles; Carbamates; Cyclopropanes; Fluorenes; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Proline; Renal Insufficiency, Chronic; Ritonavir; Sofosbuvir; Sulfonamides; Treatment Outcome; Uracil; Valine

2018
Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus-Infected Persons: Results From ERCHIVES.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2017, Sep-15, Volume: 65, Issue:6

    Interferon-based regimens are associated with a substantial survival benefit for persons infected with hepatitis C virus (HCV). Survival data with direct-acting antiviral agents are not available. We conducted this study to quantify the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir (PrOD) and ledipasvir/sofosbuvir (LDV/SOF) regimens upon mortality.. In the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a well-established national cohort of HCV-infected Veterans, we identified HCV-infected persons initiated on PrOD or LDV/SOF, excluding those with human immunodeficiency virus, hepatitis B surface antigen positivity, hepatocellular carcinoma, or missing HCV RNA or FIB-4 scores. For each case, we identified a propensity score-matched control never initiated on treatment. Primary outcome was survival. Outcomes were assessed using frequency of events, Kaplan-Meier curves, and Cox proportional hazards regression analyses.. We identified 1473 persons on PrOD, 5497 on LDV/SOF, and 6970 propensity score-matched untreated persons. Treated persons were more likely to be obese and have cirrhosis, but less likely to have stage 3-5 chronic kidney disease (CKD), alcohol or drug abuse or dependence diagnosis, and anemia. The proportion of persons who died was higher in the untreated group compared with either treatment group (PrOD, 0.3%; LDV/SOF, 1.4%; untreated controls, 2.5%; P < .001). A significantly larger percentage of treated patients survived to 18 months of follow-up, compared with untreated controls (P < .001). In multivariable Cox regression analysis, treatment with either regimen (hazard ratio [HR], 0.43; 95% confidence interval [CI], .33-.57) and attainment of sustained virologic response (SVR) were associated with significantly lower mortality (HR, 0.57; 95% CI, .33-.99).. Treatment with PrOD or LDV/SOF and SVR are associated with a significant mortality benefit, apparent within the first 18 months of treatment.

    Topics: 2-Naphthylamine; Aged; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Cyclopropanes; Drug Therapy, Combination; Female; Fluorenes; Hepatitis C, Chronic; Humans; Kaplan-Meier Estimate; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Propensity Score; Proportional Hazards Models; Ritonavir; Sofosbuvir; Sulfonamides; Survival Rate; Sustained Virologic Response; Uracil; Valine

2017
Cost-effectiveness of currently recommended direct-acting antiviral treatments in patients infected with genotypes 1 or 4 hepatitis C virus in the US.
    Journal of medical economics, 2016, Volume: 19, Issue:8

    This study compared the cost-effectiveness of direct-acting antiviral therapies currently recommended for treating genotypes (GT) 1 and 4 chronic hepatitis C (CHC) patients in the US.. A cost-effectiveness analysis of treatments for CHC from a US payer's perspective over a lifelong time horizon was performed. A Markov model based on the natural history of CHC was used for a population that included treatment-naïve and -experienced patients. Treatment alternatives considered for GT1 included ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D ± R), sofosbuvir + ledipasvir (SOF/LDV), sofosbuvir + simeprevir (SOF + SMV), simeprevir + pegylated interferon/ribavirin (SMV + PR) and no treatment (NT). For GT4 treatments, ombitasvir/paritaprevir/ritonavir + ribavirin (2D + R), SOF/LDV and NT were compared. Transition probabilities, utilities and costs were obtained from published literature. Outcomes included rates of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver-related death (LrD), total costs, life-years and quality-adjusted life-years (QALYs). Costs and QALYs were used to calculate incremental cost-effectiveness ratios.. In GT1 patients, 3D ± R and SOF-containing regimens have similar long-term outcomes; 3D ± R had the lowest lifetime risks of all liver disease outcomes: CC = 30.2%, DCC = 5.0 %, HCC = 6.8%, LT = 1.9% and LrD = 9.2%. In GT1 patients, 3D ± R had the lowest cost and the highest QALYs. As a result, 3D ± R dominated these treatment options. In GT4 patients, 2D + R had lower rates of liver morbidity and mortality, lower cost and more QALYs than SOF/LDV and NT.. While the results are based on input values, which were obtained from a variety of heterogeneous sources-including clinical trials, the findings were robust across a plausible range of input values, as demonstrated in probabilistic sensitivity analyses.. Among currently recommended treatments for GT1 and GT4 in the US, 3D ± R (for GT1) and 2D + R (for GT4) have a favorable cost-effectiveness profile.

    Topics: 2-Naphthylamine; Adult; Aged; Aged, 80 and over; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Cost-Benefit Analysis; Cyclopropanes; Drug Therapy, Combination; Female; Fibrosis; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Liver Neoplasms; Macrocyclic Compounds; Male; Markov Chains; Middle Aged; Models, Econometric; Proline; Quality-Adjusted Life Years; Ribavirin; Simeprevir; Sofosbuvir; Sulfonamides; Uracil; Valine

2016
Comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin vs. ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in 6961 genotype 1 patients treated in routine medical practice.
    Alimentary pharmacology & therapeutics, 2016, Volume: 44, Issue:4

    Real-world data are needed to inform hepatitis C virus (HCV) treatment decisions.. To assess the comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) vs. ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ± RBV in genotype 1 HCV patients treated in routine medical practice.. Observational intent-to-treat cohort of genotype 1 patients initiating 8 or 12 weeks of LDV/SOF ± RBV or 12 weeks of OPrD ± RBV. Sustained virological response (SVR) required RNA below the limit of quantification at least 10 weeks after end of treatment.. 6961 patients initiated LDV/SOF (N = 4478), LDV/SOF + RBV (N = 1269), OPrD (N = 297), and OPrD + RBV (N = 917) at 126 facilities. Intention-to-treat SVR rates were 91.4% (3813/4170) for LDV/SOF, 90.0% (1098/1220) for LDV/SOF + RBV, 95.1% (269/283) for OPrD and 85.8% (746/869) for OPrD + RBV. SVR rates in those completing 8 weeks of LDV/SOF were 91.7% (1223/1333) and 12 weeks of LDV/SOF 94.6% (2475/2615), LDV/SOF + RBV 92.2% (1033/1120), OPrD 98.0% (248/253) and OPrD + RBV 95.5% (705/738). Significant predictors of SVR were African American race (OR 0.71, 95%CI 0.59-0.86, P < 0.001), body mass index (BMI) > 30 kg/m(2) (OR 0.73, 95% CI 0.60-0.89, P = 0.002), FIB4 > 3.25 (OR 0.60, 95% CI 0.49-0.72, P < 0.001), OPrD + RBV compared to LDV/SOF (OR 0.60, 95% CI 0.48-0.76, P < 0.001) and subtype 1b (OR 1.38, 95% CI 1.11-1.71, P = 0.003). For those completing 12 weeks, FIB-4 > 3.25 and high BMI remained significant predictors.. In this robust real-world cohort, SVR rates were similar to clinical trials. FIB-4 > 3.25 and high BMI were significant negative predictors of SVR. Reduced odds of SVR in African Americans and with OPrD + RBV likely arose from excess early discontinuation as these factors were no longer significant, when limited to patients completing a 12-week course.

    Topics: 2-Naphthylamine; Adult; Aged; Aged, 80 and over; Anilides; Antiviral Agents; Benzimidazoles; Black or African American; Carbamates; Cyclopropanes; Drug Combinations; Drug Therapy, Combination; Female; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Macrocyclic Compounds; Male; Middle Aged; Proline; Ribavirin; Ritonavir; RNA, Viral; Sofosbuvir; Sulfonamides; Sustained Virologic Response; Uracil; Valine; Young Adult

2016
Cost-Effectiveness of Genotype 1 Chronic Hepatitis C Virus Treatments in Patients Coinfected with Human Immunodeficiency Virus in the United States.
    Advances in therapy, 2016, Volume: 33, Issue:8

    New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients.. A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER).. In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R.. In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV.

    Topics: 2-Naphthylamine; Adult; Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Cost-Benefit Analysis; Cyclopropanes; Disease Progression; Drug Therapy, Combination; Fluorenes; Genotype; Hepacivirus; Hepatitis C, Chronic; HIV Infections; Humans; Interferon-alpha; Lactams, Macrocyclic; Liver Cirrhosis; Liver Neoplasms; Macrocyclic Compounds; Markov Chains; Middle Aged; Polyethylene Glycols; Proline; Quality-Adjusted Life Years; Recombinant Proteins; Ribavirin; Ritonavir; Sofosbuvir; Sulfonamides; United States; Uracil; Valine

2016
Hepatitis C Treatment With Direct-Acting Antivirals in Kidney Transplant: Preliminary Results From a Multicenter Study.
    Transplantation proceedings, 2016, Volume: 48, Issue:9

    Hepatitis C (HC) is a very relevant negative prognosis factor for graft and transplant recipient survival. New direct-acting antivirals (DAAs) allow us to solve this problem in an effective way. It is crucial to understand their real impact in our daily practice. We analyzed treatment results with DAA, free of interferon, in kidney transplant recipients (KTRs) from 15 Spanish hospitals (Grupo Español de Actualización en Trasplante), regarding effectiveness, tolerance, and impact on immunosuppression, renal function-proteinuria, and diabetes. One hundred nineteen KTRs were included (9 combined liver-kidney transplants). The main DAA used was sofobusvir (91%) combined with ledipasvir (55%), simeprevir (14%), or daclatasvir (13%); in 9 cases (7%), a paritaprevir-ritonavir-ombitasvir-dasabuvir combination (3D) was used; Ribavirin was used as a coadjuvant in 18%. Side effects were limited (23.5%) and without relevance in general, except in 7 patients for whom we needed to interrupt the treatment due to neurotoxicity (1) caused by drug interaction (3D and tacrolimus) or anemia (3) by Ribavirin or others. Ninety-four patients had completed the treatment when data were analyzed: virological response was seen in 97.8% % of cases. Liver function analysis improved: 84% normal versus 21% before starting the treatment (P < .001). Renal function and proteinuria did not change. Tacrolimus level at the end of DAA-treatment was significantly lower with respect to the beginning (5.8 ± 2.1 ng/mL vs. 7.4 ± 1.8 ng/mL, P = .03), despite a slight increase in the dose (2.6 mg/d vs. 2.3 mg/d, P = .17). DAA are highly effective in the treatment of hepatitis C in KTRs with good tolerance in general, making it possible to solve the problem and have a good chance to improve the prognosis in our transplantation patients. The use of these therapies in KTRs requires special control and coordination with digestive professionals, especially if 3D or Ribavirin is used.

    Topics: Antiviral Agents; Benzimidazoles; Carbamates; Cyclopropanes; Drug Therapy, Combination; Fluorenes; Hepacivirus; Hepatitis C; Humans; Imidazoles; Immunosuppression Therapy; Kidney Transplantation; Lactams, Macrocyclic; Macrocyclic Compounds; Postoperative Complications; Proline; Prospective Studies; Pyrrolidines; Retrospective Studies; Ribavirin; Simeprevir; Sofosbuvir; Spain; Sulfonamides; Treatment Outcome; Valine

2016
Thousands of patients in England to get new hepatitis C drugs.
    BMJ (Clinical research ed.), 2015, Jun-12, Volume: 350

    Topics: Anilides; Antiviral Agents; Benzimidazoles; Carbamates; Cyclopropanes; England; Fluorenes; Hepatitis C, Chronic; Heterocyclic Compounds, 3-Ring; Humans; Imidazoles; Lactams, Macrocyclic; Macrocyclic Compounds; Proline; Public Health; Pyrrolidines; Simeprevir; Sofosbuvir; Sulfonamides; Uridine Monophosphate; Valine

2015
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