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Association Between Apolipoprotein E 4 and Neuropsychiatric Symptoms During Interferon Treatment for Chronic Hepatitis C

Received July 26, 2002; revision received April 15, 2003; accepted April 28, 2003. From the Departments of Surgery and Psychiatry, The University of Queensland, Brisbane, Australia; and the Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Population and Clinical Sciences Division, the Queensland Institute of Medical Research, Brisbane, Australia. Address reprint requests to Dr. Kelly, Associate Professor of Psychiatry and Director of Mental Health, St. Vincent's Hospital, Darlinghurst Rd., Darlinghurst, NSW 2010 Australia; briankelly{at}stvincents.com.au (e-mail).

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon . These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) 4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon . A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an 4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an 4 allele. Additionally, patients with an 4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon . Prospective studies evaluating the importance of APOE in susceptibility to interferon -induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon -induced neuropsychiatric complications.

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