The pharmacogenetics of OATP1B1 variants and their impact on the pharmacokinetics and efficacy of elbasvir/grazoprevir

2019 ◽  
Vol 20 (9) ◽  
pp. 631-641
Author(s):  
Zifang Guo ◽  
Luzelena Caro ◽  
Michael N Robertson ◽  
Peggy Hwang ◽  
Patricia Hoover ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Retrospective Analysis ◽  
Genetic Variants ◽  
Sustained Virologic Response ◽  
Area Under Curve ◽  
Risk Allele ◽  
Geometric Mean ◽  
Virologic Response

Aim: To evaluate the effect of SLCO1B1 genetic variants on grazoprevir pharmacokinetics and efficacy. Methods: A retrospective analysis of 1578 hepatitis C virus-infected participants from ten Phase II/III clinical trials. Results: Relative to noncarriers of the risk allele, geometric mean ratios (95% CI) of grazoprevir area under curve (AUC)0–24 were: rs4149056 (risk allele C), one copy, 1.13 (1.06–1.21), two copies, 1.43 (1.16–1.77); and rs11045819 (risk allele A), one copy, 0.93 (0.87–1.00); two copies, 0.78 (0.61–1.00). The rs2306283 variant was not associated with grazoprevir exposure. None of the SLCO1B1 variants were associated with sustained virologic response. Conclusion: Genetic variants in SLCO1B1 were associated with modest changes in grazoprevir pharmacokinetics, but not with meaningful differences in efficacy.

scholarly journals Impact of IFNL4 Genetic Variants on Sustained Virologic Response and Viremia in Hepatitis C Virus Genotype 3 Patients

2019 ◽  
Vol 39 (10) ◽  
pp. 642-649 ◽  
Author(s):  
Vincent Pedergnana ◽  
William L. Irving ◽  
Eleanor Barnes ◽  
John McLauchlan ◽  
Chris C.A. Spencer ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Variants ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Genotype 3 ◽  
Virus Genotype

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two

2017 ◽  
Vol 26 (3) ◽  
pp. 309-317 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranța Iacob ◽  
Roxana Șirli ◽  
Anca Trifan ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Real Life ◽  
Virologic Response ◽  
Position Paper ◽  
Hcv Infection ◽  
End Stage Liver Disease ◽  
End Stage

Background & Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the second part of the Society’s recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania. Abbreviations: CKD: Chronic kidney disease; DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESDL: End-stage liver disease; FCH: Fibrosing cholestatic hepatitis; GT: Genotype; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; MELD score: Mayo-Clinic End-Stage Liver Disease score; PDC: Premature discontinuation; PWID: Persons who inject drugs; RASs: Resistance associated substitutions; RBV: Ribavirin; RCT: Randomized controlled trial; SAE: Serious adverse events; SRGH: Romanian Society of Gastroenterology and Hepatology; SVR: Sustained virologic response.

IL-21 as a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection

2017 ◽  
Vol 185 (2) ◽  
pp. 484-493 ◽  
Author(s):  
Halla Mohamed Ragab ◽  
Nabila Abd El Maksoud ◽  
Mona A. Amin ◽  
Mohab H. Halim ◽  
Nour A. Abdulla ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Chronic Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Hepatitis C Virus Infection ◽  
Chronic Hepatitis C Virus

scholarly journals Sofosbuvir Plus Daclatasvir in Treatment of Chronic Hepatitis C Genotype 4 Infection in a Cohort of Egyptian Patients: An Experiment the Size of Egyptian Village

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Ossama Ashraf Ahmed ◽  
Eslam Safwat ◽  
Mohamed Omar Khalifa ◽  
Ahmed I. Elshafie ◽  
Mohamed Hassan Ahmed Fouad ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Adverse Events ◽  
Chronic Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
World Health ◽  
Genotype 4 ◽  
Positive Results

Background and Aims. As indicated by the World Health Organization (WHO), Egypt is positioned as the country with the world’s highest prevalence of Hepatitis C virus (HCV). HCV is transmitted through unexamined blood transfusions, different employments of syringes, and poor cleansing, as per the WHO. Our study aimed at screening and management of chronic hepatitis C genotype 4 infected patients in Bardeen village, Sharkeya Governorate, Egypt, with Sofosbuvir plus Daclatasvir, as well as estimating the safety and efficacy of that regimen. Methods. Screening of adult patients in Bardeen village was done from March 2016 till November 2016 using hepatitis C virus antibodies by third-generation ELISA testing. Positive results were confirmed by PCR. Patients eligible for treatment received Sofosbuvir 400 mg and Daclatasvir 60 mg daily for 12 weeks and were assessed for sustained virologic response at 12 weeks following the end of treatment (SVR 12). Results. Out of 2047 subjects screened for hepatitis C virus, 249 (12.2%) showed positive results. 221 out of those 249 subjects (88.7%) had detectable RNA by PCR. Treatment of eligible patients (183 patients) with Sofosbuvir plus Daclatasvir for 12 weeks resulted in 96% achievement of sustained virologic response at week 12. Adverse events were tolerable. Conclusion. Sofosbuvir plus Daclatasvir regimen is safe and effective for treatment of chronic hepatitis C Genotype 4 infected patients with minimal adverse events. HCV eradication program implemented in Egypt can be a model for other countries with HCV and limited resources. The availability of generic drugs in Egypt will help much in eradication of the virus.

scholarly journals Hepatitis C Virus Infection and Renal Disorders

2019 ◽  
Vol 3 (1) ◽  
pp. 1-14
Author(s):  
Maurizio Salvadori ◽  
Aris Tsalouchos
Keyword(s):  
Hepatitis C Virus ◽  
Renal Transplantation ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Virologic Response ◽  
Antiviral Drugs ◽  
Renal Diseases ◽  
Renal Disorders ◽  
Direct Acting Antiviral ◽  
Direct Acting

Hepatitis C virus (HCV) infection is frequently associated with extrahepatic disorders, among which renal diseases are frequent. This article highlights the most frequent HCV-associated renal disorders, the impact of HCV infection on chronic renal disease and renal transplantation, and the role of current direct-acting antiviral therapies. HCV is associated with membranoproliferative glomerulonephritis, acceleration of end-stage renal diseases in patients with glomerulopathies, and a higher risk of death in patients affected by chronic kidney disease. Before the introduction of direct-acting antiviral drugs as treatment modality, renal transplantation was a challenging clinical problem because the drugs available until 2011 obtained a poor sustained virologic response, had several side effects, and caused acute rejection when used after transplantation. The knowledge of the viral structure and its replication allowed the discovery of new classes of direct-acting antiviral drugs that revolutionized this scenario. These new drugs are comparatively more effective and safer. Accumulating evidence suggests that it is possible to cure HCV-related glomerulonephritis, and obtain a sustained virologic response in patients with renal failure, or on dialysis, before commencing transplantation. Finally, it became possible to transplant HCV-positive kidneys into HCV-positive or HCV-negative recipients.

scholarly journals Sustained Virologic Response of Patients Hospitalized Compared With Those Not Hospitalized During Treatment for Hepatitis C Virus With Direct-Acting Antivirals

2020 ◽  
pp. 106002802096411
Author(s):  
Anthony J. Gentene ◽  
Allison M. Bell ◽  
Alicia Pence ◽  
Kelly Thomas ◽  
Collin Jakubecz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Sustained Virologic Response ◽  
Disease Patient ◽  
Virologic Response ◽  
Great Success ◽  
Direct Acting Antivirals ◽  
Inpatient Mortality ◽  
Direct Acting

Background: Direct-acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) have resulted in great success through high attainment of sustained virologic response (SVR). Risk factors for DAA treatment failure are important to identify because of worsened outcomes with failure and high treatment cost. Objective: We sought to identify whether hospitalization during treatment affects SVR. The primary outcome was the difference in SVR at 12 weeks after treatment Methods: This multicenter, single health system retrospective cohort review compared achievement of SVR between patients hospitalized during DAA treatment for HCV with those not hospitalized during treatment. Results: Patients in the hospitalized cohort (n = 94) had more severe disease at baseline than nonhospitalized patients (n = 167) as indicated through higher Model for End-Stage Liver Disease (MELD) scores, Fibrosis-4 scores, and imaging-suggested or biopsy-confirmed cirrhosis. Patients hospitalized during treatment had lower SVR rates compared with those not hospitalized (87.2% vs 95.2%; P = 0.043) but failed to reach significance when inpatient mortality was excluded on secondary analysis (91.1% vs 95.2%; P = 0.195). Patients who were hospitalized and did not achieve SVR had higher MELD scores, were more likely to have intensive care unit stay, and had longer hospital stay compared with those who achieved SVR. Of 94 patients, 93 provided home supply of DAAs during hospitalization. Conclusion and Relevance: Patients hospitalized during DAA treatment for HCV had reduced rates of SVR. This reduced SVR rate may be driven by inpatient mortality and severity of liver disease. Patient education to bring home supply of medication for use during admission is an effective intervention.

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