Short-term use of antiepileptic drugs is neurotoxic to the immature brain

Previous studies have shown that the long-term use of antiepileptic drugs can cause nervous system damage. However, short-term antiepileptic drug treatment is frequently given to in-fants, especially neonates, to control seizure. Whether the short-term use of antiepileptic drugs is neurotoxic remains unclear. In the present study, immature rats, 3–21 days of age, were intraperitoneally injected with phenobarbital and/or topiramate for 3 consecutive days. Hema-toxylin-eosin and immunohistochemical staining revealed that phenobarbital and topiramate, individually or in combination, were cytotoxic to hippocampal CA1 neurons and inhibited the expression of GluR1 and NR2B, excitatory glutamate receptor subunits. Furthermore, the com-bination of the two drugs caused greater damage than either drug alone. The results demonstrate that the short-term use of antiepileptic drugs damages neurons in the immature brain and that the combined use of antiepileptic drugs exacerbates damage. Our ifndings suggest that clinicians should consider the potential neurotoxic risk associated with the combined use of antiepileptic drugs in the treatment of seizure.

Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naive chronic hepatitis B patients: a prospective and randomized controlled trial

Background:The efficacy of entecavir(ETV)add-on peg-interferon therapy compared with ETV monotherapy in treatment-naive hepatitis B virus(HBV)patients remains controversial.We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.Methods:All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital(China).Eligible HBV patients(n=144)were randomly divided(1:1)to receive either ETV monotherapy(n=70)or peg-interferon add-on therapy from week 26 to 52(«=74).Patients were followed-up for at least 2 years.Indexes including hepatitis B surface antigen(HBsAg)and hepatitis B e antigen(HBeAg)seroconversion rate,sustained virologic response,transient elastography value,and histological scores were evaluated every 3 months until the end of the study.The rate of patients with HBsAg loss was defined as the primary endpoint criteria.Results:At week 26,no patient achieved HBsAg seroconversion in either group.At week 52,one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group.The monotherapy group showed significantly better liver function recovery results than the combination therapy group.At week 78,one patient in the combination group had HBsAg seroconverted.At week 104,only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy.The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline.Both groups showed a favorable decrease in alpha-fetoprotein(monotherapy:4.5[2.8,7.1]vs.2.2[1.8,3.1]ng/mL,P<0.001;combination therapy:5.7[3.0,18.8]vs.3.2[2.0,4.3]ng/mL,P<0.001)and an improved result of liver biopsy examination scores.The combination group showed a better improvement in histology compared with the monotherapy group(mean transient elastography value 6.6[4.9,9.8]vs.7.8[5.4,11.1]kPa,P=0.028).But there was no significant difference in HBsAg conversion rate(1.8%[1/56]i^s.4.1%[3/73],P=0.809)and HBeAg conversion rate(12.5%[7/56]i/s.11.0%[8/73],P=0.787),as well as HBV-DNA,sustained virologic response(93.2%vs.98.5%,P=0.150)between the two groups.Conclusions:Both therapies supported liver function recovery and histology improvement.Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy.However,combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.Trial registration:ClinicalTrials.gov:NCT02849132;https://clinicaltrials.gov/ct2/show/NCT02849132.