Relationship between the hepatitis C viral load and the serum interferon concentration during the first week of peginterferon-alpha-2b-ribavirin combination therapy.

In chronic hepatitis C virus (HCV) infections, the current standard of care (combination therapy with pegylated alpha interferon (PEG-IFNalpha) and ribavirin) is only effective in around 50% of cases. The aim of the present study was to analyze the relationship between the HCV load and the PEG-IFN concentration during the first week of treatment. Fifteen treatment-naive patients with chronic hepatitis C infection (genotypes 1, 2, 3, and 4) underwent PEG-IFNα-2b/ribavirin combination therapy. Blood samples were collected before the first injection (T(0)) and then at different time points until the next injection a week later. The PEG-IFN concentration and the HCV load were assayed. The serum interferon concentration peaked 2 days after the first injection (mean value for the study population; T(max) = 40.9 hr; C(max) = 490 pg/ml) and a trough in viral load was seen at day 3. The PEG-IFNalpha-2b concentration decreased from day 2 to day 7, enabling a viral rebound in all patients. The change in viral load between day 0 and day 3 differed significantly according to whether the patients were responders at week 12 (Deltalog d(0)/d(3) = 2.729 +/- 1.419 log(10) IU/ml) or not (Deltalog d(0)/d(3) = 1.102 +/- 0.472 log(10) IU/ml). Our results emphasize the potential clinical importance of achieving viral decay immediately after initiation of interferon-ribavirin combination therapy. J. Med. Virol. 82:1640-1646, 2010. 2010 Wiley-Liss, Inc.

Quantification of different human alpha interferon subtypes and pegylated interferon activities by measuring MxA promoter activation.

Alpha interferons (alpha-IFNs) are potent biologically active proteins synthesized and secreted by somatic cells during viral infection. Quantification of alpha-IFN concentrations in biological samples is used for diagnosis. More recently, recombinant IFNs have been used as antiviral, antiproliferative, and immunomodulatory therapeutic agents, and particularly for the treatment of chronic hepatitis C virus infection. For this purpose, IFN has recently been coupled to polyethylene glycol (PEG) to improve the pharmacokinetic properties. The measure of alpha-IFN in biological samples from treated patients could be useful to ensure compliance to therapy and the true IFN activity in relation to viral decay during follow-up. In particular, it could be used to monitor the PEG-IFN concentration in patients treated for hepatitis C virus infection. The most frequently used test is a bioassay based on the antiviral property of the IFN, but the assay is not highly reproducible. Here, we present a reporter test based on MxA promoter activation of chloramphenicol acetyltransferase expression (Mx-CAT). MxA is an antiviral protein induced and tightly regulated by alpha-IFN. The Mx-CAT assay showed good reproducibility of 15% and was suitable to quantify PEG-IFN and numerous other alpha-IFN subtypes as well, despite a differential MxA promoter activation in relation with the subtype. A good correlation was obtained with the reporter assay and a commercial enzyme-linked immunosorbent assay on samples from treated patients. This test could be useful for monitoring IFN therapy of chronically infected hepatitis C virus-infected patients treated with the standard IFN, PEG-IFN, and probably forthcoming recombinant IFNs.