Severe drug-induced liver injury (DILI) associated with benznidazole therapy for Chagas' disease

Chagas’ disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, endemic in Latin America and sporadic in many parts of the world, affects 6–7 million people.1 Although the efficacy of drug treatment of late-stage CD remains uncertain,2 it is expected to prevent severe cardiac, intestinal and/or neurological complications. Since 1970, only two drugs have been available for CD treatment: benznidazole and nifurtimox. Benznidazole is highly metabolized by the liver.3 Both drugs are associated with a high rate of drug discontinuation due to side effects, such as skin reactions, leucopenia and neuropathy. A mild elevation of transaminases is sometimes observed. Discontinuation of benznidazole due to serious toxic effects is rarely necessary, and adverse effects usually disappear when treatment is stopped.4–6 Here we describe the case of a patient treated with benznidazole for CD who developed severe liver toxicity. A 68-year-old woman who was born in El Salvador and migrated in Italy in 2010, taking levetiracetam (500 mg twice per day) for epilepsy, was diagnosed in June 2021 with chronic CD according to WHO criteria. The disease staging did not reveal organ involvement. Liver ultrasonography showed a mild hyperechogenic structure.