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 (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 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].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.

• Authors: Hwalih Han, Mazen Noureddin, Michael Witthaus, Yoon J Park, Jay H Hoofnagle, T Jake Liang, Yaron Rotman
• Journal: Journal of hepatology (J Hepatol) Vol. 59 Issue 5 Pg. 957-63 (Nov 2013) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 23850879 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier B.V.

Chemical References

• Antiviral Agents
• Chemokine CXCL10
• IFNL3 protein, human
• Interferon-alpha
• Interleukins
• RNA, Viral
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• Interferons
• peginterferon alfa-2a

Topics

• Adult
• Antiviral Agents (therapeutic use)
• Body Temperature (genetics, physiology)
• Chemokine CXCL10 (blood)
• Female
• Fever (genetics, physiopathology)
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (blood, drug therapy)
• Humans
• Interferon-alpha (therapeutic use)
• Interferons
• Interleukins (genetics)
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Polymorphism, Single Nucleotide (genetics)
• Prospective Studies
• RNA, Viral (blood)
• Recombinant Proteins (therapeutic use)
• Retrospective Studies
• Ribavirin (therapeutic use)
• Treatment Outcome