Reuters Health Information
Jul 25, 2013
By Will Boggs, MD
NEW YORK (Reuters Health) Jul 25 - Patients with chronic hepatitis C virus (HCV) who become febrile after peginterferon alfa-2a (PEG-IFN) injection are more likely to have a virological response than those who don't, a retrospective study suggests.
"Many patients find it difficult to complete interferon-based regimens because of the side-effects," Dr. Yaron Rotman from National Institutes of Health, Bethesda, Maryland told Reuters Health by email. "Clinicians can use our findings as a tool to encourage patients who suffer from side effects, to let them know that these actually suggest they are responding, and to help convince them to persist and maintain their compliance and adherence to treatment."
Fever commonly follows PEG-IFN injection, but the factors that predict the magnitude of this febrile response and its association with the antiviral efficacy of PEG-IFN are unknown.
To explore this issue, Dr. Rotman and colleagues reviewed data from a prospective trial of 60 treatment-naive adults with chronic HCV.
Most (57%) were infected with genotype 1, and their average age was 52 years.
As reported online July 11th in the Journal of Hepatology, oral temperature rose above 38.0 C in 20 patients (33%) at a median of 12.5 hours after injection.
The maximum temperature increase correlated strongly with the first phase virological decline, with a 0.49 C increase for each 1 log10 decline in viral levels.
Temperature increases did not differ significantly by gender. The link between temperature increase and virological decline also didn't differ by gender, nor by the presence or absence of cirrhosis or the viral genotype.
The maximum temperature change was higher for patients with the IL28B-related SNP rs12979860 CC genotype, and the correlation of maximum temperature increase with virological decline was limited to patients with the CC genotype.
Despite the link of temperature change with virological response, maximum temperature change did not predict either rapid or sustained virological response very well, and it was only a weak predictor of early virological response.
"Since the spike of fever is independent of virological predictors of response, it could potentially serve in the research setting as a tool to tease out host interferon-responsiveness from viral- and liver-related factors," the researchers say.
"The clinical importance of the study is in the novel appreciation that medication side-effects are closely linked to its efficacy," Dr. Rotman said.
"Of course," he continued, "the interferon-induced fever is not causing viral clearance, and we are not claiming that, but its occurrence early on (in the first 24 hours) can give patients and their doctors an inclination that the drug is actually doing its job."
Dr. Hans Van Vlierberghe from Ghent University Hospital in Belgium, who has published work on chronic HCV treatment, told Reuters Health by email, "This is a very nice and elegant study, monitoring temperature after peginterferon administration and linking the rise in temperature to response. However, treatment of hepatitis C is evolving more and more to an interferon-free combination schedule, making the observation by the authors less and less relevant."
Dr. Rotman added, "I would have to credit the first author, Hwalih Han, BSN, BS, the research nurse specialist, who has done a significant amount of the work on this study under my mentorship. Research nurses are not typically involved in the analysis and writing of clinical trial manuscripts; our work shows how physicians and nurses can work in synergy not only in clinical care, but also in research, especially in areas that straddle both disciplines."
J Hepatol 2013.