Abstracts

Rationale:
Ketogenic Diet (KD) is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of KD, usually with long term use. However, there is limited data to implicate KD in acute hepatocellular toxicity.
Method:
We describe 2 patients who were started on KD and showed acute, asymptomatic hepatocellular toxicity during initiation, which rapidly improved once KD was stopped or tapered off. 1 patient was on medications known to be hepatotoxic and the other was not.
Results:
patient 1:  2-year-old boy with Dravet syndrome due to de novo pathogenic variant- A1783T in SCN1A gene.  Patient was diagnosed with seizures at 4 months of age, with prolonged right hemibody convulsions in the setting of febrile illness. Later, he developed other unprovoked seizure types, including atonic head drops and atypical absence seizures He was tried on multiple medications, and was later maintained on Valproic acid (VPA), clobazam and epidiolex, with improvement in both duration and frequency of seizures. Pre-initiation KD labs had been obtained by the referring physician and were normal During inpatient KD initiation, serial comprehensive metabolic panels and blood ketone levels were obtained.  Liver enzymes, both AST and ALT showed significant elevation (figure 1), corresponding to successive increases in the ratio of ketogenic diet, with AST showing an 8 fold elevation at the highest ratio of 3:1 and ALT showing a corresponding 6 fold elevation. ALP remained stable.  Patient remained asymptomatic and tolerated the KD well, with no notable side effects. Because of evidence of acute hepatocellular toxicity showing a direct correlation with increasing ratios of ketogenic diet, the diet was weaned off over 3 days and the liver enzymes showed a corresponding reduction, with no changes made to antiepileptic medications. patient 2: 12 months old girl, who was born at 30 weeks of gestation due to preeclampsia.  She was found to have multiple bilateral intraparenchymal hemorrhagic lesions resulting in neonatal seizures, which subsequently evolved to multifocal cystic encephalomalacia and ex vacuo hydrocephalus, with resultant global developmental delay and cortical visual impairment At around 5 months of age, she developed epileptic spasms and tonic seizures of varying and asymmetric semiology. EEG showed multifocal epileptiform discharges.  She failed multiple medications. At the time of evaluation in the KD clinic, family had stopped all seizure medications except for topiramate at 1mg/kg/day because they felt that medications resulted in side effects and did not help with seizures. Pre-initiation KD labs had been obtained by the referring physician and were normal KD was started inpatient  and the same laboratory testing was performed.  As with prior patient, both AST and ALT showed significant elevations (figure 2), after starting the diet at 1:1 ratio, with AST showing an 8 fold increase the day after introduction of ketogenic diet and ALT showing a 13 fold increase the day after introduction of the ketogenic diet.  ALP levels continued to be normal.  Because of significant elevation in transaminases, ketogenic diet was stopped on day 2 and transaminases started showing a downward trend during the hospitalization and returned back to normal within a month of discharge.
Conclusion:
acute hepatocellular toxicity can be a side effect during initiation of KD, with or without the presence of hepatotoxic medications. We recommend checking liver function tests daily (along with blood ketones and electrolytes) during inpatient initiation of KD, especially in infants and toddlers.
Funding:
:none