Interferon-alpha therapy in patients with hepatitis C virus infection increases plasma phenylalanine and the phenylalanine to tyrosine ratio
Abstract
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-α (IFN-α) 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-α and weight-based ribavirin. Results were compared to HCV-RNA titers and concentrations of neopterin. IFN-α treatment was associated with a drop of HCV load (from median 6.3 to 3.2 log10 copies/μL; 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 μM, Tyr was 98.8 μM, and Phe/Tyr was 1.23 μmol/μmol, and under therapy median Phe concentrations increased to 132.6 μM 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-α therapy. Data indicate that activity of enzyme phenylalanine 4-hydroxylase becomes impaired. Future studies should show whether side effects of IFN-α treatment such as mood changes and depression will be associated with the alterations of Phe metabolism.
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Plasma Phen/Tyr ratios are increased in IFN-alpha-treated subjects compared to controls, negatively correlate with CSF DA and HVA, and positively correlate with fatigue.
“Plasma Phen/Tyr ratios were increased in IFN-alpha-treated subjects compared to controls (Felger et al., 2012b, Zoller et al., 2012), and negatively correlated with CSF concentrations of DA and HVA, and positively correlated with fatigue, in IFN-alpha-treated patients (Felger et al., 2012b).”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Zoller et al., 2012
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- Authors
- Zoller, H., Schloegl, A., Schroecksnadel, S., Vogel, W., & Fuchs, D.
- Affiliations
- Innsbruck Medical University (AT)
- Corresponding author
- Fuchs, Dietmar
- Venue
- Journal of Interferon & Cytokine Research
- Publisher
- SAGE Publications
- Published
- 2012-05
- Volume
- 32
- Issue
- 5
- Pages
- 216-220
- ISSN
- 1079-9907 (ISSN-L)
- 1557-7465
- OpenAlex
- W1985575431
- Cited by
- 33
- References
- 49
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 1 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Interferon & Cytokine Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- interferon-alpha, hepatitis C virus, phenylalanine, phenylalanine/tyrosine ratio, amino acid metabolism, ribavirin, pegylated interferon, neopterin, HCV RNA viral load, depression, mood changes
- MeSH terms
- Adult, Chromatography, High Pressure Liquid, Female, Hepatitis, Chronic, Humans, Immunotherapy, Male, Middle Aged, Phenylalanine, Polyethylene Glycols, Recombinant Proteins, Ribavirin, Tyrosine, Hepacivirus, Treatment Outcome, Interferon-alpha, Viral Load, Mood Disorders, Biosynthetic Pathways
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