Interferon-Alpha Therapy in Patients with Hepatitis C Virus Infection Increases Plasma Phenylalanine and the Phenylalanine to Tyrosine Ratio

Higher blood levels of the essential amino acid phenylalanine (Phe) together with impaired conversion of Phe to tyrosine (Tyr) have been observed in patients suffering from inflammatory conditions. Data suggest that inflammatory responses may interfere with Phe metabolism. This study aimed to investigate whether treatment with cytokine interferon-alpha (IFN-alpha) influences Phe concentrations and the Phe to Tyr ratios (Phe/Tyr) measured by HPLC. Twenty-five patients (9 females, 16 males, aged mean+/-SD: 44.5+/-11.0 years) with hepatitis C virus (HCV) infection were examined before and after 1 month of effective antiviral therapy with pegylated IFN-alpha and weight-based ribavirin. Results were compared to HCV-RNA titers and concentrations of neopterin. IFN-alpha treatment was associated with a drop of HCV load (from median 6.3 to 3.2 log10 copies/mu L; P<0.001) and an increase of neopterin concentrations (from median 4.83 to 12.1 nM; P=0.001) which confirms effectiveness of therapy. Before therapy, median Phe concentration were 123.9 mu M, Tyr was 98.8 mu M, and Phe/Tyr was 1.23 mu mol/mu mol, and under therapy median Phe concentrations increased to 132.6 mu M and Phe/Tyr to 1.33 (both P<0.05; paired rank test), Tyr levels remained unchanged. The increase of Phe concentrations and of Phe/Tyr in HCV infected individuals is caused by IFN-alpha therapy. Data indicate that activity of enzyme phenylalanine 4-hydroxylase becomes impaired. Future studies should show whether side effects of IFN-alpha treatment such as mood changes and depression will be associated with the alterations of Phe metabolism.