Liver toxicity of sitaxentan in pulmonary arterial hypertension.

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 ERA therapy causes liver injury are not clear. It has been suggested that ERAs or their metabolites competitively inhibit a bile salt transporter pump, leading to intracellular accumulation of bile salts, but other mechanisms cannot be excluded.