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

Hwalih Han, Mazen Noureddin, Michael Witthaus, Yoon J. Park, Jay H. Hoofnagle, T. Jake Liang, Yaron Rotman

Research output: Contribution to journalArticle

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 24 h 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 12.5 h. ΔTmax was strongly associated with 1st phase virological decline (r = 0.59, p max (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.

Original languageEnglish (US)
Pages (from-to)957-963
Number of pages7
JournalJournal of Hepatology
Volume59
Issue number5
DOIs
StatePublished - Nov 2013
Externally publishedYes

Fingerprint

Chronic Hepatitis C
Interferons
Genotype
Injections
Temperature
Blood Cells
Chemokine CXCL10
Ribavirin
Interferon-gamma
Area Under Curve
Antiviral Agents
Single Nucleotide Polymorphism
Blood Proteins
Fever
Clinical Trials
RNA
peginterferon alfa-2a
Therapeutics
Serum
Genes

Keywords

  • Fever
  • Hepatitis C
  • IL28B
  • Interferon alfa
  • Temperature
  • Treatment

ASJC Scopus subject areas

  • Hepatology

Cite this

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; Noureddin, Mazen; Witthaus, Michael; Park, Yoon J.; Hoofnagle, Jay H.; Liang, T. Jake; Rotman, Yaron.

In: Journal of Hepatology, Vol. 59, No. 5, 11.2013, p. 957-963.

Research output: Contribution to journalArticle

Han, Hwalih ; Noureddin, Mazen ; Witthaus, Michael ; Park, Yoon J. ; Hoofnagle, Jay H. ; Liang, T. Jake ; Rotman, Yaron. / Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype. In: Journal of Hepatology. 2013 ; Vol. 59, No. 5. pp. 957-963.
@article{b69ae071e9f34c8f8737456375c1a6a9,
title = "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-na{\"i}ve 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 24 h 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 12.5 h. ΔTmax was strongly associated with 1st phase virological decline (r = 0.59, p max (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.",
keywords = "Fever, Hepatitis C, IL28B, Interferon alfa, Temperature, Treatment",
author = "Hwalih Han and Mazen Noureddin and Michael Witthaus and Park, {Yoon J.} and Hoofnagle, {Jay H.} and Liang, {T. Jake} and Yaron Rotman",
year = "2013",
month = "11",
doi = "10.1016/j.jhep.2013.07.004",
language = "English (US)",
volume = "59",
pages = "957--963",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype

AU - Han, Hwalih

AU - Noureddin, Mazen

AU - Witthaus, Michael

AU - Park, Yoon J.

AU - Hoofnagle, Jay H.

AU - Liang, T. Jake

AU - Rotman, Yaron

PY - 2013/11

Y1 - 2013/11

N2 - 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 24 h 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 12.5 h. ΔTmax was strongly associated with 1st phase virological decline (r = 0.59, p max (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.

AB - 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 24 h 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 12.5 h. ΔTmax was strongly associated with 1st phase virological decline (r = 0.59, p max (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.

KW - Fever

KW - Hepatitis C

KW - IL28B

KW - Interferon alfa

KW - Temperature

KW - Treatment

UR - http://www.scopus.com/inward/record.url?scp=84885947858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885947858&partnerID=8YFLogxK

U2 - 10.1016/j.jhep.2013.07.004

DO - 10.1016/j.jhep.2013.07.004

M3 - Article

C2 - 23850879

AN - SCOPUS:84885947858

VL - 59

SP - 957

EP - 963

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 5

ER -