Research On The Changes Of The Liver Function And Lipids In Children With Epilepsy Who Used Sodium Valproate And The Influential Factors Of These Changes

OBJECTIVE: Epilepsy is the common disease of the nervous system in children. It seriously affects the physical and psychological health of the children with epilepsy. The morbidity is about 0.4%～0.6%. Sodium Valproate (VPA) is a kind of broad spectrum anti-epilepsy drug which was widely used because of its slight side effects and high efficacy. Though there are so many merits of VPA, the hepatotoxicity should not be ignored. It can cause obesity in children and have an influence on the quality of the patients' life in some extent. It can also increase the onset risk of the cardiovascular disease. Reports about the side effects of VPA can be found world wide, but no systemic trials reported before. This study was designed to investigate the changes of the liver function and lipid levels before and three months after VPA treatment, and analyze the influential factors. The aim is to know: 1. the change of liver function index in children with epilepsy who use VPA and the characteristic of this change, 2. the change of body mass index (BMI) and lipid levels in children with epilepsy who use VPA and the influence of this change on the onset risk of the cardiovascular disease, 3. the influential factors of the change of the liver function and lipid levels, in order to guide the clinic rational administration of VPA and minimize the side effects.METHODS: 54 cases who admitted to our Pediatrics outpatient department, during March 2005 to December 2006 in Shandong University Qilu Hospital were included as the experimental group. The selection standard: ①Epilepsy diagnose was confirmed by the classification of the types of the children epileptic seizures which was formulated in entire country pediatric neurology conference in 1983, clinic manifestations and EEG or 24 hour EEG. All the patients have no history of VPA usage before, and would be prescribed with VPA only. ②No history of other drugs usage that will affect the liver function and lipid level. ③No history of endocrine disease. ④Normal diet condition. The dosage of VPA is about 10~40mg/kg.d. All patients were divided into three groups(①②③group) based on the age (0～3years, 3～8years, 8～13years). Patients in every age group were given three different kinds of VPA dosage( Ⅰ 10～20mg/kg.d, Ⅱ 20～30mg/kg.d, Ⅲ30～40mg/kg.d ). All 54 patients were divided into nine treated groups. Every group had six patients. 63 unimpaired children who admitted to our Pediatrics outpatient department were included as the control group. We detected the BMI, ALT, AST, GGT, ALB, GLB, TG, TC, HDL-C and LDL-C. We compared the differences of the levels between the control group and the experimental group before VPA-treated. We also compared the differences of the levels between the experimental group before VPA-treated and three months after VPA-treated. We analyzed the characteristic of these changes and the relations between these changes with age or dosage.RESULTS: 1. There were no statistic difference of BMI, ALT, AST, GGT, ALB, GLB, TG, TC, HDL-C, LDL-C levels between the control group and the experimental group before VPA-treated (P>0.05).2. When comparing the parameters' levels between the initial testing and 3-month follow up, we found that levels of their BMI, ALT, AST, GGT, TG, LDL-C in the later group were all significantly higher than those of the former ones (P<0.05), while the HDL-C level decreased significantly (P<0.05). There were no significant changes in the levels of TC, ALB, GLB observed (P>0.05) .3. The difference of the parameters levels between before VPA-treated and 3-month after VPA-treated were considered as dependent variable (AALT=ALT level 3-month after VPA-treated- ALT level before VPA-treated, etc). According to multiple factors analysis of variance, the changes of ALT, AST and GGT levels had siginificant differences among the different age and dosage groups (P<0.05). The changes of ALT, AST, GGT levels in young age group apparently greater than those in other two different age groups (P<0.05). There were no difference of the changes of ALT, AST, GGT levels between other two different age groups (P>0.05) . The changes of ALT, AST, GGT levels in high dosage group apparently greater than those in other two different dosage groups (P<0.05). There were no difference of the changes of ALT, AST, GGT levels between other two different dosage groups (P>0.05).There was interaction between age and dosage factor (P<0.05). The difference of the changes of the parameter' levels would be found in different age groups used different VPA dosage. With increasing of age, the changes of ALT, AST and GGT levels in high dosage group (Ⅲ group) present obviously descending tendency, while the low and middle dosage group (Ⅰ Ⅱ group) present no variational tendency. With increasing of the dosage, the changes of ALT, AST and GGT levels in young age group (①group) present obviously ascending tendency, while the middle and old age group (②③group) present no variational tendency. The severe increasing of ALT, AST and GGT levels were only found in young age (①group) used high dosage (Ⅲgroup). The influences of VPA on the changes of ALT, AST, GGT levels were predominantly shown in young age group. With the increasing of the age, the effects of the dosage on the changes of liver enzymes would diminish. The changes of LDL-C levels had siginificant differences among the different dosage groups (P<0.05). The changes of LDL-C levels in high dosage group apparently greater than those in other two different dosage groups (P<0.05). There were no difference of the changes of LDL-C levels between other two different dosage groups (P>0.05) . The changes of LDL-C levels had no siginificant differences among the different age groups (P>0.05) . There was no interaction between age and dosage factor (P>0.05) . The influence of VPA on the changes of LDL-C level was also predominantly shown in young age group. With increasing of the dosage, the changes would increase. The changes of BMI, TG, HDL-C levels had no difference among different age groups and different dosage groups (P>0.05) .4. According to the simple liner regression, only in young age group, there were simple linear regression relations between the changes of ALT, AST, GGT, LDL-C levels and VPA dosage (ΔALT: R~2=0.581; b=1.223, P<0.001; ΔAST: R~2=0.554; b=1.467, P<0.001; ΔGGT: R~2=0.575; b=1.222, P<0.001; ΔLDL-C: R~2=0.440; b=0.031, P<0.01). With increasing of the dosage, the changes would increase. In other two age groups, there were no simple linear regression relation between the changes of ALT, AST, GGT, LDL-C levels and VPA dosage.CONCLUSION: 1. BMI of the patients increased at three months after VPA-treated. Some patients had become obesity. This change had no relation to age and dosage. During this time, control the food and drink appropriately had advantage to regulate the weight.2. The liver enzymes would obviously increase at the early stage after VPA-treated, especially ALT and AST. This change had relation with age and dosage. There was interaction between age and dosage factor. The differences of the changes of the parameter' levels would be found in different age groups used different VPA dosages. With the increasing of the age, the effects of the dosage on the changes of liver enzymes would diminish. The influences of VPA on the changes of ALT, AST, GGT levels were predominantly shown in young age group. Simple linear regression relations were only found in youge age group (①group) between the changes of liver enzyme levels and VPA dosage. The severe increasing of the liver enzymes was only found in young age (①group) used high dosage (Ⅲgroup). So for the children younger than three years, using the high dosage of VPA should be avoided.3. The lipids would obviously change at the early stage after VPA-treated. This change would increase the onset risk of the cardiovascular disease. Only the change of LDL-C had relation to the dosage. The influence of VPA on the changes of LDL-C level was also predominantly shown in young age group. During the longtime to use VPA, it is necessary to monitor the lipids of the patients.