Low SVR Rates in Clinical Practice for Treating Genotype 1 Chronic Hepatitis C with Protease Inhibitors Boceprevir and Telaprevir

Dubin, Perry H.; Sclair, Seth N.; Rico, Rafael Calpena; Boehme, Amelia K; Chen, Emerson Y.; Martin, Paul; Lee, William M.

doi:10.1007/s10620-014-3374-1

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…In treatment-experienced patients with compensated cirrhosis Child A, the SVR was 39%–46% ( 15 ). In a real-world setting, it was shown that the treatment effect with BOC or TVR tended to be lower for cirrhotic patients, 38.9% compared to 65% for non-cirrhotic patients ( 16 ). Moreover, it was shown that host factors such as cirrhosis, ethnicity, albumin level, viral load ≥800,000 IU/L, and BMI ≥30 were significant predictors for response in a multivariate logistic regression analysis ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

“…In a real-world setting, it was shown that the treatment effect with BOC or TVR tended to be lower for cirrhotic patients, 38.9% compared to 65% for non-cirrhotic patients ( 16 ). Moreover, it was shown that host factors such as cirrhosis, ethnicity, albumin level, viral load ≥800,000 IU/L, and BMI ≥30 were significant predictors for response in a multivariate logistic regression analysis ( 16 ). Other studies supported these findings and also added age, gender, stage of fibrosis, and previous treatment experience to the list ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

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The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort

Kjellin

Wesslén

Löfblad

et al. 2018

Upsala Journal of Medical Sciences

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BackgroundThe clinical experience with protease-inhibitor (PI) triple regimen appears disappointing regarding effect, side effects, high work load, and costs. This real-world study evaluates baseline and emerging resistance-associated substitutions (RASs) and their significance for treatment outcome.MethodThirty-six genotype 1a/b patients treated according to Swedish recommendations during 2011–2013 with triple therapy including pegylated interferon and ribavirin in combination with a protease-inhibitor, either boceprevir (BOC) or telaprevir (TVR), were retrospectively evaluated. Frozen serum samples from the patients were tested for resistance with pan-genotypic population sequencing.ResultsOverall, 56% (20/36) of the patients achieved sustained viral response (SVR). The SVR was comparable between BOC (64%; 9/14) and TVR (50%; 11/22) (p = 0.07), and the IL28B type non-CC (48%; 12/25) and CC (46%; 6/13) (p = 0.77). The SVR was higher in patients without cirrhosis (89.5%; 17/19) (p < 0.0005), in treatment-naïve patients (70%; 14/20) (p = 0.02), and those with low viral load (<800,000 IU/mL) (66.7%; 8/12) (p < 0.0002), compared to those with cirrhosis (17.6%; 3/17), treatment-experienced (37.5%; 6/16), and high viral load (>800,000 IU/mL) (50%; 12/24).ConclusionPI triple regimes were highly effective in treatment-naïve patients without cirrhosis, but in this real-world cohort an inferior effect was evident in cirrhotic and treatment-experienced patients. Although tested on a limited sample, the baseline resistance testing seems to have no impact on prediction of therapy outcome. The reason could be that the baseline RASs T54S and V55A have relatively low resistance towards BOC and TVR. Emerging RASs, mainly R155K, with known high resistance to BOC and TVR were frequently found in non-responders.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort

Kjellin

Wesslén

Löfblad

et al. 2018

Upsala Journal of Medical Sciences

View full text Add to dashboard Cite

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“…However, these treatments are extremely expensive, and have restricted virus genotypes for application. [7][8][9]. HCV contains two heavily N-linked glycosylated envelope glycoproteins, E1 and E2, which assemble as a non-covalent heterodimeric complex retained in the endoplasmic reticulum (ER) during biogenesis [10,11].…”

Section: Introductionmentioning

confidence: 99%

N-glycosylation-mutated HCV envelope glycoprotein complex enhances antigen-presenting activity and cellular and neutralizing antibody responses

Ren

Min

Liu

et al. 2016

Biochimica et Biophysica Acta (BBA) - General Subjects

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Glecaprevir/Pibrentasvir Induced Cholestatic Jaundice in a HCV Patient with Renal Failure. A Case Presentation

Caroleo

Cimellaro

et al. 2019

CDS

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Background: Direct-acting Antivirals (DAA) are currently used in the treatment of chronic HCV infection. In patients with renal failure Glecaprevir/Pibrentasvir (genotype 1-6) is recommended for its safety and efficacy. Case Presentation: Although these pharmacological characteristics, an adverse drug reaction (ADR) has been reported during Glecaprevir/Pibrentasvir treatment, such as the development of cholestatic jaundice in an elderly patient with chronic HCV (genotype 2) infection. At examination, patient was jaundiced associated with intense pruritus. Results: Ultrasound and laboratory biochemical tests excluded a liver failure (e.g. liver cancer, and liver lithiasis) or pancreatic cancer while Naranjo probability scale (score 6) suggested an association between cholestatic jaundice and Glecaprevir/Pibrentasvir administration. About 1 month after drug discontinuation, an improvement has been documented in both jaundice and pruritus, with a normalization in bilirubin levels (total bilirubin: 0.96 mg/dL), HCV-RNA was undetected also. It is worth mentioning that although we reported the development of cholestatic jaundice upon treatment with Glecaprevir/Pibrentasvir we recorded a clinical efficacy (HCV-RNA <15 IU/L) after 4 weeks from the beginning of the treatment, with a complete remission of clinical symptoms until 7 months after drug discontinuation. Conclusion: These data support the clinical efficacy of Glecaprevir/Pibrentasvir association in elderly patients, despite the sub-optimal period of treatment.

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Low SVR Rates in Clinical Practice for Treating Genotype 1 Chronic Hepatitis C with Protease Inhibitors Boceprevir and Telaprevir

Cited by 3 publications

References 6 publications

The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort

The effect of the first-generation HCV-protease inhibitors boceprevir and telaprevir and the relation to baseline NS3 resistance mutations in genotype 1: experience from a small Swedish cohort

N-glycosylation-mutated HCV envelope glycoprotein complex enhances antigen-presenting activity and cellular and neutralizing antibody responses

Glecaprevir/Pibrentasvir Induced Cholestatic Jaundice in a HCV Patient with Renal Failure. A Case Presentation

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