Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus

Thompson, Alexander; Muir, Andrew J.; Sulkowski, Mark S.; Ge, Dongliang; Fellay, Jacques; Shianna, Kevin V.; Urban, Thomas; Afdhal, Nezam H.; Jacobson, Ira M.; Esteban, Rafael; Poordad, Fred; Lawitz, Eric; McCone, Jonathan; Shiffman, Mitchell L.; Galler, Greg; Lee, William M.; Reindollar, Robert; King, John W.; Kwo, Paul Y.; Ghalib, Reem; Freilich, Bradley; Nyberg, Lisa M.; Zeuzem, Stefan; Poynard, Thierry; Vock, David M.; Pieper, Karen S.; Patel, Keyur; Tillmann, Hans L.; Noviello, Stephanie; Koury, Kenneth; Pedicone, Lisa D.; Brass, Clifford A.; Albrecht, Janice K.; Goldstein, David B.; McHutchison, John G.

doi:10.1053/j.gastro.2010.04.013

Cited by 626 publications

(620 citation statements)

References 21 publications

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“…Of patients with the C/C genotype, 82% had an SVR, compared with 75% for genotype C/T and 58% for genotype T/T (P ¼ 0.0046 for trend). In contrast to previous observations in North American patients with genotype 1 HCV, 3,8 the SVR rate for genotype C/T patients was intermediate between genotype C/C and T/T patients, suggesting the possibility of a more additive effect of the C allele than in the previous setting. Differences between IL28B genotypes were greatest among patients who did not have an RVR.…”

Section: Il28b For Other Hcv Genotypes and In The Context Of Coinfectioncontrasting

confidence: 99%

“…8 Further studies show that the difference can be detected in the first 48 hours of treatment (Fig. 2).…”

Section: Il28b Genotype and Viral Kineticsmentioning

confidence: 84%

“…8 These factors suggest that if IL28B genotyping is used, it should be considered along with other baseline predictors of response and virological status at week 4.…”

Section: Clinical Role For Pharmacogenetics In Hepatitis Cmentioning

confidence: 99%

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Hepatitis C pharmacogenetics: State of the art in 2010

Afdhal¹,

McHutchison²,

Zeuzem³

et al. 2011

Hepatology

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133

104

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In 2009, a correlated set of polymorphisms in the region of the interleukin-28B (IL28B) gene were associated with clearance of genotype 1 hepatitis C virus (HCV) in patients treated with pegylated interferon-alfa and ribavirin. The same polymorphisms were subsequently associated with spontaneous clearance of HCV in untreated patients. The link between IL28B genotype and HCV clearance may impact decisions regarding initiation of current therapy, the design and interpretation of clinical studies, the economics of treatment, and the process of regulatory approval for new anti-HCV therapeutic agents. (HEPATOLOGY 2011;53:336-345)

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Section: Il28b For Other Hcv Genotypes and In The Context Of Coinfectioncontrasting

confidence: 99%

“…8 Further studies show that the difference can be detected in the first 48 hours of treatment (Fig. 2).…”

Section: Il28b Genotype and Viral Kineticsmentioning

confidence: 84%

See 1 more Smart Citation

Hepatitis C pharmacogenetics: State of the art in 2010

Afdhal¹,

McHutchison²,

Zeuzem³

et al. 2011

Hepatology

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133

104

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“…Treatment efficacy was described according to; non-response, early, end of treatment (ETR) and sustained virologic responses (SVR), and relapse after therapy. 19 …”

Section: Data Collectionmentioning

confidence: 99%

Hepatitis C Virus Treatment in the ‘Real-World’: How Well Do ‘Real’ Patients Respond?

Friedman

Green

Weber

et al. 2014

Journal of Clinical and Experimental Hepatology

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Background: Published clinical trials of the treatment of HCV are largely multicentre prospective pharmaceutical trials. Patients in clinical trials tend to have more favorable outcomes than patients in the 'real-world', due to strict patient selection and differences in treatment conditions and available resources. Objectives: To assess the outcomes of Hepatitis C infected patients treated at the Barwon Health Liver Clinic with combination Pegylated interferon (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a treatment response. Methods: Retrospective review of patients who received treatment for Hepatitis C at our institution's Liver Clinic from January 2001-September 2011. Patient demographics, comorbidities, treatment-related parameters and side effects were extracted from medical records and analyzed. Results: A total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range 20-68 years) commenced treatment. The most common genotype was genotype 3 (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed treatment and had end of treatment data available. 107 of 182 patients, (58.8%) for whom sustained virologic response (SVR) rate data was available achieved an SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3 respectively. The response rate was significantly lower in 29 patients with documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict treatment response in our cohort. Side effects reported in 81.6% of patients included general malaise, hematological disturbance and psychiatric issues, and necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26 patients (13.7%). Conclusions: Response rates to combination PEG-IFN and RBV therapy at our institution are comparable to other 'real-world' and pharmaceutical registration trials. Side effects of combination therapy were prominent but resulted in fewer discontinuations of therapy compared to pharmaceutical trials. ( J CLIN EXP HEPATOL 2014;4:214-220)

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“…The SVR rates for PR-treated HCV genotype 1 patients with the IL-28 CC genotype were more than 2-fold greater than the rates for patients with the CT or TT genotype. [14][15] Data regarding the use of IL-28B with the addition of directacting antiviral agents to PR are emerging, and as the discovery of IL-28B occurred after the large phase 3 trials with telaprevir and boceprevir had been initiated, we will need to wait for more complete data sets in naive patients. In the SPRINT-2 trial, IL-28 data were available for 62% of the patients (653/1048).…”

Section: Areas Of Uncertaintymentioning

confidence: 99%

Boceprevir

and

Kwo

2011

Hepatology

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A 52-year-old male executive who is asymptomatic is evaluated for abnormal liver biochemical tests. The aspartate aminotransferase level is 138 U/L, and the alanine aminotransferase level is 164 U/L; the bilirubin, alkaline phosphatase, and albumin levels and the complete blood counts are normal. The international normalized ratio is 1.1, and the serum creatinine level is 0.9 mg/dL. The hepatitis C virus (HCV) RNA level is 1,600,000 IU/mL, and the genotype is 1B. The patient has read about boceprevir and wants to know whether he is a candidate for treatment with this drug. He also wants to know whether he really requires liver biopsy before the initiation of treatment.Will you use boceprevir in this patient? How will you determine whether he is responding to the drug, how long will you give him the medication, and how will you monitor him for side effects? How will you determine that treatment-related anemia is related to boceprevir and is not related to ribavirin? Which side effects of boceprevir will warrant the discontinuation of treatment? Will your approach vary with the genotype for the interleukin-28 (IL-28) polymorphism?

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Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus

Cited by 626 publications

References 21 publications

Hepatitis C pharmacogenetics: State of the art in 2010

Hepatitis C pharmacogenetics: State of the art in 2010

Hepatitis C Virus Treatment in the ‘Real-World’: How Well Do ‘Real’ Patients Respond?

Boceprevir

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