Over this period, α-interferon has remained the backbone of antiviral regimens and the CNS effects of this administered cytokine have been intensively studied during treatment. It is well established that α-interferon induces depressive symptoms in patients with HCV infection, which generally peak after 12 weeks of therapy.
Other neuropsychiatric selleck chemicals effects include fatigue, irritability, anxiety, and cognitive symptoms such as memory disturbances and concentration problems. The underlying mechanisms of α-interferon-induced depression have been studied by researchers with an interest in the inflammatory hypothesis of depression and include alterations in the hypothalamic-pituitary-adrenal axis, perturbations in the metabolism of major neurotransmitters, and the activation of the enzyme indoleamine-2,3-dioxygenase (IDO), which leads to the degradation of tryptophan into neurotoxic pathways. In parallel, predictors of α-interferon-induced depression have been sought and include genetic polymorphisms in the FK866 chemical structure serotonin transporter and immune genes, blood levels of certain cytokines, e.g., interleukin-6, and other peripheral biomarkers such as docosahexaenoic acid. However, there has been relatively little attention paid to the interaction between HCV-associated
cognitive impairment and the on-treatment and delayed effects of α-interferon-containing therapy. Fontana et al. studied neurocognitive function in a cohort of patients with advanced fibrosis and cirrhosis who had previously failed
to respond to pegylated α-interferon and ribavirin in the HALT-C study. When retreated for a prolonged period with low-dose maintenance pegylated α-interferon, they found no effect of treatment on cognitive function after up to 48 months. At baseline there was significant impairment in 28% of patients but no significant positive or negative effect of interferon was seen through treatment, raising the ADP ribosylation factor possibility that this group had minimal hepatic encephalopathy (MHE), which was unaffected by treatment. This study was not designed to evaluate the effect of viral eradication on neurocognitive function. In contrast, in an earlier study before the one published in this issue by Kraus et al., the same investigators reported a significant negative impact of α-interferon on vigilance, attention, and working memory in patients after 3-8 months of full-dose α-interferon-based treatment. There was a return to baseline cognitive function 6 weeks after the end of treatment but, again, the study was not designed to evaluate the effect of successful viral eradication. In contrast to the HALT-C cohort, this cohort had milder liver disease and the adverse effect of treatment was probably related to an absence of preexisting MHE and a higher dose of α-interferon.