AASLD 2011: Fever Signals Responsiveness to Pegylated Interferon for Hepatitis C


People who have an increase in body temperature soon after starting interferon-based therapy for chronic hepatitis C virus (HCV) infection are more likely to experience early virological response, according to a presentation at the American Association for the Study of Liver Disease (AASLD) Liver Meeting last month in San Francisco.

Rather than directly targeting HCV, interferon works by stimulating the body's immune response. This can lead to a variety of flu-like symptoms including fever, loss of appetite, and muscle aches. But it is not known how these side effects relate to antiviral activity.

Hwalih Hanand colleagues from the National Institutes of Health evaluated whether temperature changes after starting interferon reflect responsiveness to pegylated interferon, as assessed by viral kinetics, serum cytokine levels, and treatment response.

The study included 60 previously untreated chronic hepatitis C patients who started standard therapy using pegylated interferon plus ribavirin. Half were men, nearly 60% were white, about 20% each were black and Asian, and the mean age was 52 years. A majority (57%) had difficult-to-treat HCV genotype 1, one-third had genotypes 2 or 3, and 10% had genotypes 4, 5, or 6.

The researchers measured body temperature with an oral thermometer before the first injection of pegylated interferon and at 8, 16, and 24 hours thereafter, and determined the maximum temperature increase from baseline within the first 24 hours, or Tmax.

Serum HCV viral load was measured at baseline, at 6, 24, 48, and 72 hours, and then weekly for the first 4 weeks of treatment, and used to calculate the first and second phase slope of HCV decline. Levels of interferon gamma-inducible protein 10 (IP-10) were also assessed for a subset of patients at baseline and at 6 and 24 hours after treatment initiation.


"Temperature increase after the initial injection of pegylated interferon is closely associated with interferon responsiveness, as reflected by the correlation with serum IP-10 increase, virological decline, and IL28B genotype," the researchers concluded. "The lack of difference between genotypes pinpoints its association with host-responsiveness factors."

As an easily measurable marker, they suggested, temperature "may be incorporated as a surrogate of more expensive and elaborate tests in future models of responsiveness to interferon-based treatment."

Investigator affiliation: Liver Diseases Branch, NIDDK, NIH, Bethesda, MD.



H Han, M Noureddin, YJ Park, et al. Changes in Oral Temperature After the Initial Injection of Peginterferon Alfa-2a in Patients with Chronic Hepatitis C Reflect Host-Interferon Responsiveness. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 487.