Dataset Information

Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.

ABSTRACT: BACKGROUND & AIMS:Interferon treatment for chronic hepatitis C is associated with non-specific symptoms including fever. We aimed to determine the association of temperature changes with interferon antiviral activity. METHODS:60 treatment-naïve patients with chronic hepatitis C (67% genotype 1/4/6, 33% genotype 2/3) were admitted to start peginterferon alfa-2a and ribavirin in a clinical trial. Temperature was measured at baseline and 3 times daily for the first 24h and the maximal increase from baseline during that time (?Tmax) was determined. Serum HCV-RNA, interferon-gamma-inducible protein-10 (IP-10) and expression of interferon-stimulated genes (ISGs - CD274, ISG15, RSAD2, IRF7, CXCL10) in peripheral blood mononuclear cells (PBMCs) were measured at very early time points, and response kinetics calculated. The IL28B single nucleotide polymorphism, rs12979860, was genotyped. RESULTS:Temperatures rose by 1.2±0.8°C, peaking after 12.5h. ?Tmax was strongly associated with 1st phase virological decline (r=0.59, p<0.0001) and was independent of gender, cirrhosis, viral genotype or baseline HCV-RNA. The association with 1st phase decline was seen in patients with rs12979860CC genotype (r = 0.65, p <0.0001) but not in CT/TT (r = 0.13, p = 0.53) and patients with CC genotype had a higher DTmax (1.4 ± 0.8 C vs. 0.8 ± 0.6 +C, p = 0.001). DTmax was associated with 6- and 24-h induction of serum IP-10 and of PBMC ISG expression, but only in patients with rs12979860CC [corrected].?Tmax weakly predicted early virological response (AUC=0.68, CI 0.49-0.88). CONCLUSIONS:Temperature rise following peginterferon injection is closely associated with virological response and is modulated by IL28B polymorphism, reflecting host interferon-responsiveness.

SUBMITTER: Han H

PROVIDER: S-EPMC3856983 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.

Han Hwalih H Noureddin Mazen M Witthaus Michael M Park Yoon J YJ Hoofnagle Jay H JH Liang T Jake TJ Rotman Yaron Y

Journal of hepatology 20130710 5

<h4>Background & aims</h4>Interferon treatment for chronic hepatitis C is associated with non-specific symptoms including fever. We aimed to determine the association of temperature changes with interferon antiviral activity.<h4>Methods</h4>60 treatment-naïve patients with chronic hepatitis C (67% genotype 1/4/6, 33% genotype 2/3) were admitted to start peginterferon alfa-2a and ribavirin in a clinical trial. Temperature was measured at baseline and 3 times daily for the first 24h and the maxima ...[more]

PMID: 23850879

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Project description:BACKGROUND:A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. METHODS:Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. RESULTS:A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (?800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. CONCLUSIONS:In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment, mainly due to hepatobiliary-related events, and more Lambda patients were lost to follow-up.

Dataset Information

Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.

Publications

Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.

Similar Datasets

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