HCV patients, psychopathology and tryptophan metabolism: analysis of the effects of pegylated interferon plus ribavirin treatment

Abstract Aims: Depression and other psychiatric disorders are frequent in HCV-infected patients, especially during interferon treatment. The molecular mechanism(s) maderlying this finding is still unknown but it has been suggested that HCV and/or interferon administration may increase indoleamine 2,3-dioxygenase (IDO) activity, and reduce plasma tryptophan (TRP) levels and brain serotonin synthesis thus leading to psychopathological disorders. Methods: We studied 89 subjects: (a) 39 patients with chronic hepatitis C virus (HCV) infection and mild liver damage; (b) 39 healthy controls; and (c) 10 patients with chronic hepatitis B virus (HBV) infection. 15 of the patients with HCV infection were re-evaluated after antiviral treatment with pegylated interferon α-2a plus ribavirin leading to viral eradication. We measured serum TRP and kynurenine levels and IDO activity in macrophages. Furthermore, each patient had an accurate psychopathological evaluation. Results: HCV-infected patients had lower (28%) serum TRP and kynuxenine levels than healthy volunteers or HBV-infected patients with comparable liver damage. Depression and anxiety symptoms were particularly common in HCV patients. After viral clearance, macrophage IDO activity, plasma TRP and kynuxenine levels returned toward normal values and psychopathology improved. Conclusion: Our study shows that HCV patients have reduced serum TRP levels and confirms that they frequently suffer from anxiety and depression-related symptoms. The reduced IDO activity found in the macrophages of these patients suggests that HCV infection may hamper macrophage fmactions. After successful antiviral treatment, in spite of the expected increase of IDO activity in macrophages, we noticed that TRP and kynurenine plasma levels returned toward physiological levels and psychopathology decreased significantly.