Abstracts

Multiple studies from the 1970s to the 1990s report elevated serum concentrations of gamma glutamyl transferase (GGT) in 50 to 80% of patients treated with antiepileptic drugs (AEDs). To a great extent, it has become standard practice to attribute elevated GGT to AED enzyme induction and not to hepatotoxicity. However, these studies were performed on patients predominantly treated with phenobarbital, phenytoin, and primidone, medications now infrequently used to treat children. We intermittently receive inquiries regarding elevated GGT from primary care physicians who have obtained a [ldquo]liver panel[rdquo] on patients taking AEDs. Many of the newer AEDs are not enzyme inducers, and there is little information regarding their effect on GGT. The current study reexamines the frequency of elevated GGT to determine how it has changed over the last 10 years. It is our standard practice to obtain a metabolic panel, which includes liver functions tests (LFTs), on all admissions to the pediatric inpatient epilepsy unit. We requested that GGT be included in this evaluation. Serum concentrations of GGT, ALT, AST were obtained prospectively on 50 consecutive admissions. These were evaluated with respect to age, sex, number and type of AEDs. There were 20 boys, 30 girls, age 1 to 18 (mean 7.9) years, 20 were on monotherapy, 30 polytherapy, 7 ketogenic diet + AED. AEDs included CBZ(4), CZP(1), FBM(16), GBP(3), LEV(18), LTG(10), OXC(5),PB(3),PHT(3), TPM(7), VPA(11), ZNS(7). There were 6 (12%) patients with elevated GGT, all on polytherapy, including 2/3 on phenobarbital, 1/3 on phenytoin, and 3/16 on felbamate. Only 2/6 had other elevated LFTs, both on felbamate. Patients on PB and PHT had 2-3 times the normal GGT. 2 of the patients on FBM had 1.2 and 1.5 times the normal GGT. The third patient, a 6 y.o. male on FBM, had 12.5 times the normal GGT with 1.5 and 2 times normal AST and ALT. This patient had been referred specifically for a GGT 125 times normal ([gt]11,000), which had occurred following the addition of VPA to his treatment. The VPA had been stopped, and the GGT was decreasing. With changes in AED treatment over the last 10 years, there has been a change in the frequency of elevated GGT. We found 12% as opposed to the 50[ndash]80% previously reported. Our 6 patients on PB and PHT had a 50% frequency of 2-3 X normal GGT, consistent with past reports. These were isolated, with AST and ALT normal, suggesting enzyme induction as the cause. Only 3/44 (6.8%) of the patients on the other AEDs had an elevated GGT, all associated with FBM, and 2 with other LFT elevations. The greatest elevation in GGT was with FBM, although VPA appeared to contribute in this case. These are more suggestive of hepatotoxicity. Elevations of GGT need to be evaluated carefully.