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A growing body of evidence suggests that patients infected with hepatitis C virus (HCV) have a high prevalence of psychiatric disorders. Antiviral treatment, particularly interferon (IFN), may induce an increase in the incidence of psychiatric symptoms observed in HCV patients.This study aimed to identify the possible psychiatric complications in patients infected chronically with HCV and follow up these complications on treatment with pegylated IFN plus ribavirin.This is a longitudinal follow-up, comparative (case–control) study conducted on 90 patients, all of whom were subjected to a semistructured interview, psychometric assessment by International Classification of Diseases-10 Symptom Checklist for Mental Disorder version 1.1 for psychiatric evaluation, laboratory investigations to exclude decompensate liver cases, liver biopsy, and abdominal ultrasonography.HCV prevalence was found to be significantly higher in the age group of 30–40 years. Results of the International Classification of Diseases-10 symptom checklist showed prevalence of psychiatric complications linked to HCV infection before therapy, which included generalized anxiety disorder; these complications increased after treatment, such as mixed anxiety and depression and moderate depression. HCV infection independent of IFN therapy and hepatitis B virus infection caused mild depression and mixed anxiety and depression.HCV-related psychiatric consequences and HCV therapy-related psychiatric complications should be included in the differential diagnosis of patients, and patients should be assessed through consultation liaison psychiatry.