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 language | English (US) |
|---|---|
| Pages (from-to) | 957-963 |
| Number of pages | 7 |
| Journal | Journal of Hepatology |
| Volume | 59 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2013 |
| Externally published | Yes |
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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 journal › Article
}
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 -