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

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-naive 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 (ΔT max ) 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. ΔT max was strongly associated with 1st phase virological decline (r=0.59, p p p =0.53) and patients with CC genotype had a higher ΔT max (1.4±0.8°C vs. 0.8±0.6°C, p =0.001). ΔT max was associated with 6- and 24-h induction of serum IP-10 and of PBMC ISG expression, but only in patients with rs12989760CC. ΔT max 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.