Liver toxicity of sitaxentan in pulmonary arterial hypertension

To the Editors: Ambrisentan, bosentan and sitaxentan are endothelin receptor antagonist (ERA) drugs approved for the treatment of patients with pulmonary arterial hypertension (PAH) and are included in the treatment algorithm of the 2009 pulmonary hypertension (PH) guidelines of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) 1. Hepatotoxicity is a frequent side-effect of ERA therapy, which is contra-indicated in patients with mild to severe hepatic impairment (Child–Pugh class B–C) and elevated serum aminotransferases prior to initiation of treatment. In addition, liver function testing on a monthly basis is recommended in PAH patients treated with these compounds, in order to detect an increase in the serum aminotransferases 1. In most cases, liver injury is dose-related and reversible with dose reduction or drug discontinuation, suggesting that hepatotoxicity is caused by a dose-dependent toxic effect. The exact mechanisms by which …