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

J Hepatol. 2013 Nov;59(5):957-63. doi: 10.1016/j.jhep.2013.07.004. Epub 2013 Jul 10.

Han H, Noureddin M, Witthaus M, Park YJ, Hoofnagle JH, Liang TJ, Rotman Y.

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.

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 (ΔTmax) 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. ΔTmax 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 rs12989760CC genotype (r=0.65, p<0.0001) but not in CC/CT (r=0.13, p=0.53) and patients with CC genotype had a higher ΔTmax (1.4±0.8°C vs. 0.8±0.6°C, p=0.001). ΔTmax was associated with 6- and 24-h induction of serum IP-10 and of PBMC ISG expression, but only in patients with rs12989760CC. ΔTmax 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.

Published by Elsevier B.V.

KEYWORDS: EVR, Fever, HCV, Hepatitis C, IFN, IL28B, IP-10, ISG, Interferon alfa, PGE2, PegIFN, RVR, SVR, Temperature, Treatment, early virological response, hepatitis C virus, interferon, interferon-gamma-inducible protein-10, interferon-stimulated gene, peginterferon alfa 2a, prostaglandin E2, rapid virological response, sustained virological response

PMID: 23850879 [PubMed - in process]

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