1- Unidade de Infecciologia, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
2- Unidade de Gastrenterologia e Hepatologia Pediátirca, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
3- Serviço de Neuropediatria, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisboa
- Reunião internacional (11th Excellence in Pediatrics Conference)
Introduction: Tuberculosis (TB) is still a relevant cause of disease burden globally. Albeit infrequent, hepatotoxicity linked to antibacillary drugs accounts for most cases of adverse reactions during treatment. Known risk factors include young age, extrapulmonary tuberculosis and the use of other hepatotoxic drugs. Ketogenic diet (KD) can cause and contribute to liver toxicity. Identifying the culprit in complex cases involving multimedicated patients can be truly puzzling.
Case description: We report the case of a 5 year old boy with refractory epilepsy associated with alternating hemiparesis and hepatic cysts. He was regularly medicated with phenobarbital, zonisamide and clobazam, while also on KD for several years. He was hospitalized with mediastinal tuberculosis, under isoniazid (10 mg/kg), rifampin (10 mg/kg), ethambutol (20 mg/kg) and pyrazinamide (30 mg/kg). After 7 days, he presented with lethargy, nausea and refusal to eat. His blood tests revealed a substantial rise of both alanine aminotransferase (ALT) (549 U/L) and aspartate aminotransferase levels (857 U/L). Coagulation tests values were normal. Antibacillary therapy was suspended, phenobarbital and zonesamide doses were lowered and the ketogenic diet maintained. After an initial rise of the transaminase values (up to 913 U/L for ALT), a steady analytical normalization was observed over two weeks time, accompanied by a clinical recovery over a short period of days. After recrudescence of seizures, phenobarbital dose was augmented to 60 mg. According to the American Thoracic Society guidelines, rifampin and ethambutol were introduced without complications. However, 5 days after isoniazid introduction, a new asymptomatic twelve-fold rise of transaminases was observed. Isoniazide was suspended and after normalization of transaminase levels, pyrazinamide and levofloxacin were associated to rifampin and ethambutol. He completed six months of antibacillary drugs without further complications.
Conclusion: Although hard to prove, the re-challenge scheme leads us to admit isonizade as the most likely cause for hepatoxicity in this case. The exact involvement of anti-epileptic therapy and ketogenic diet remais unclear. KD can cause liver toxicity (7% of cases), by an unknown mechanism. Elevation of aminotransferase levels, steatosis and gallstone formation related to dyslipidemia have also been reported. There’s pressing need for pediatric specific drug re-introduction guidelines following toxic hepatitis during the course of TB treatment.
Palavras Chave: Dieta cetoǵenica, Hepatite tóxica, Tuberculose