Safety and efficacy of levetiracetam in patients with epilepsy and chronic liver disease: preliminary data

Rationale: The aim of this study was to evaluate efficacy and safety of levetiracetam (LEV) in patients with epilepsy and chronic liver disease. Methods: Eleven patients with epilepsy and chronic liver disease entered the study. Eight suffered from Focal Epilepsy and three from Generalized Epilepsy. Liver disease consisted of HCV-related epatopathy in 6 cases (2 of whom had cirrhosis), HBV-related epatopathy in 4 (2 of whom with colesthasis) and porphyria cutanea tarda in 1. At study entry all patients were already treated with antiepileptic drugs (AEDs) in mono- or polytherapy; all had uncontrolled seizures. In all patients LEV was initially given as add-on therapy,with a slow titration. Contemporarily, the associated AED treatment was slowly reduced, resulting in complete withdrawal in 3 cases. A laboratory work-up, including blood count and evaluation of liver function, was serially performed during titration and follow-up; seizure frequency was also serially evaluated, considering as baseline frequency the mean seizure frequency reported in the 6 months preceding study entry. Results: Three patients dropped out of the study because of adverse effects (2 patients, with drop out during titration) or because of adverse effects and worsening of seizures (1 patient, during follow-up). All the remaining 8 patients were responders to LEV treatment in add-on or monotherapy, with a >50% reduction of seizure frequency in 6 cases and complete disappearance of seizures in 2. None of these 8 patients showed worsening of liver function during follow-up. In all these patients follow-up lasted at least 12 months. Conclusions:With the limitations due to the small number of patients, our study suggests that LEV may be a good choice for epileptic patients with liver disease. Due to the absence of liver metabolism, LEV can be employed in high dosages, resulting in improved seizure control without liver toxicity.