Hepatic injury, liver monitoring and the beta-interferons for multiple sclerosis.
This review explores the salient issues surrounding liver injury and liver monitoring associated with beta-interferon (IFNB) treatment for multiple sclerosis (MS). Post-marketing studies have found a higher proportion of IFNB-treated MS patients with elevated aminotransferases than reported in the pivotal clinical trials. Although the risk of severe liver injury appears small, the true incidence is unknown. Post-marketing studies have shown that the greatest period of risk for the development of liver test abnormalities appears to be in the first year of IFNB treatment. The risk also increases with the more frequently administered, higher-dosage IFNBs. Males are more likely than females to develop elevated aminotransferases (> upper normal limit), although females appear at a greater risk of severe liver injury. Of the commonly used biochemical liver tests, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP) and bilirubin appear the most useful for routine monitoring of IFNB treatment. Whilst many other factors can affect liver test results, including obesity, alcohol, concomitant medications, co-morbidities and theoretically even MS itself, regular liver testing both prior and during IFNB therapy might help minimise Type A or dose/frequency dependent aminotransferase elevations. However, testing will probably not prevent the Type B idiosyncratic reactions which can result in severe hepatic injury; hence patients need to be aware, and to report hepatic side effects promptly.
Tremlett
Helen
H
Department of Medicine (Neurology) rm S159, Vancouver Hospital and Health Sciences Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. tremlett@interchange.ubc.ca
Oger
Joel
J
D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D016899:Interferon-beta / Q000009:adverse effects* / Q000627:therapeutic use; D008107:Liver Diseases / Q000201:enzymology; D008111:Liver Function Tests / Q000379:methods; D009103:Multiple Sclerosis / Q000188:drug therapy*; D011237:Predictive Value of Tests; D011358:Product Surveillance, Postmarketing; D012307:Risk Factors; D012737:Sex Factors
D016899:Interferon-beta; D001219:Aspartate Aminotransferases