左卡尼汀纠治化疗所致儿童肝功能损害

目的探讨化疗导致的肝功能损害与体内左卡尼汀水平之间的相关性,观察左卡尼汀纠治化疗所致儿童肝功能损害的临床疗效。方法 60例既往肝功能损害恶性肿瘤患儿采用随机数字法随机分为对照组和治疗组(各30例),对照组静脉给予甘草酸二铵注射液5 mg.kg-1加入5%葡萄糖注射液100 mL中滴注,治疗组轻度肝损者仅给予左卡尼汀口服液100 mg.kg-1.d-1(10 d),中、重度肝损者同时静脉给予甘草酸二铵注射液,两组均为每日给药1次。采用串联质谱法测定血浆酯酰肉碱谱和血液游离氨基酸水平。并在治疗d 6和d 11,复查血浆左卡尼汀浓度和肝功能。结果治疗组轻度肝功能损害患儿口服左卡尼汀与对照的疗效相似,而治疗组中度和重度肝损患儿联合应用左卡尼汀与甘草酸二铵治疗后肝功能恢复明显快于对照组(P=0.020 4)。治疗组的血浆游离肉碱和丙酰肉碱浓度明显高于对照组(44.20±18.59)μmol.L-1vs.(30.22±10.34)μmol.L-1,P=0.047,(2.73±1.67)μmol.L-1vs.(1.88±0.59)μmol.L-1,P=0.001],治疗组的乙酰肉碱水平高于对照组,但差异无统计学意义(P=0.061)。氨基酸谱测定分析显示:肿瘤患儿的精氨酸水平明显低于正常儿童,尤其是化疗后出现肝功能损害时下降更显著(P=0.043 1),予以干预保肝治疗后,随着肝功能恢复精氨酸水平明显升高(P=0.001 7)。化疗后肝功能损害的患儿,丙氨酸转氨酶水平与血浆游离肉碱水平之间存在明显的负相关性(r1=-0.724 8),乙酰肉碱浓度亦随着肝功能损害的加重逐渐下降(r2=-0.651 7)。结论本研究提示恶性肿瘤患儿化疗后肝功能损害与血浆酯酰肉碱低水平密切相关。给予左卡尼汀治疗可减轻化疗患儿的肝功能损害、加速肝功能的恢复。

Effects of levocarnitine on chemotherapy-induced hepatic injury

AIM To investigate the correlation between chemotherapy-induced hepatic injury and the level of levocarnitine,and observe the clinical effect of levocarnitine in the treatment of hepatic injury.METHODS Tandem mass spectrometry method was developed for the determination of acylcarnitine and free amino acid in plasma in 60 children with malignancy,which were randomly divided into control group and treat-ment group(30 in each).Patients in control group were intra-venously administered with diammonium glycyrrhizinate 5 mg·kg-1,and patients in trial group were treated with levocarnitine 100 mg·kg-1·d-1 orally and diammonium glycyrrhizinate 5 mg·kg-1 intravenously for 10 days.Plasma concentration of levocarnitine was determined and hepatic function was assessed.RESULTS Patients with mild hepatic injury in trial group and control group had similar therapeutic effectiveness.In patients with moderate and severe hepatic injury,combination of levocarnitine and diammonium glycyrrhizinate was more effective than the single use of diammonium glycyrrhizinate(P = 0.020 4).Free carnitine and propionyl carnitine concentration in plasma of trial group were higher than those of control group(44.20 ± 18.59)vs.(30.22 ± 10.34)μmol·L-1,P = 0.047,(2.73 ± 1.67)vs.(1.88 ± 0.59)μmol·L-1,P = 0.001].There was no significant difference in acetylcarnitine concentration between the two groups(P = 0.061).Spectral analysis of amino acid showed that arginine level of children with malignancy was significantly lower than that of normal children,especially after chemotherapy.There was significant negative correlation(r1 =-0.724 8)between glutamic-pyruvic transaminase and acylcarnitine in children with hepatic injury after chemotherapy,and acetylcarnitine concentration decreased gradually with the increase of hepatic injury(r2 =-0.651 7).CONCLUSION Chemotherapy-induced hepatic injury is correlated with low plasma level of levocarnitine in children with malignancy.Levocarnitine could reduce chemotherapy-induced hepatic injury and promote the recovery of hepatic function.