补肾活血化浊方干预肝豆状核变性肝纤维化的临床研究

Clinical Study of Bushen Huoxue Huazhuo Formula Intervening Hepatolenticular Degeneration

目的:探讨血清肝纤维化四项指标透明质酸酶(HA)、Ⅲ型前胶原(PIIINP)、Ⅳ型胶原(CIV)、层粘连蛋白(LN)、相关肝功能指标在肝豆状核变性肝纤维化诊断中的意义及补肾活血化浊方加减治疗肝豆状核变性肝纤维化的临床疗效。方法:检测42例肝豆状核变性患者(WD组)和42例正常人(正常组)血清中HA、PIIINP、CIV、LN、AKP及相关肝功能指标水平,其中42例肝豆状核变性患者行声辐射力脉冲成像(Acoustic Radiation Force Impulse, ARFI)技术及常规超声学检查,观测肝纤维化分期程度及脾脏厚度,进行肝纤维化的对比研究。对42例肝豆状核变性患者采用随机数字表法分为对照组和观察组,各21例。两组患者均予谷胱甘肽、二巯基丙磺酸钠(DMPs)保肝驱铜常规治疗,观察组在常规治疗基础上予口服中药复方补肾活血化浊方加减,均治疗4个疗程(8天1个疗程)。结果:肝豆状核变性肝纤维化患者(WD组)HA、PIIINP、CIV、LN四项指标水平均显著高于正常组(P<0.01),HA、PIIINP、CIV、 LN、脾脏厚度水平与纤维化分期均呈高度正相关(r=0.849、0.858、0.677、0.903、0.933,P均<0.05)。四项指标联合诊断肝纤维化的判别函数为:-12.268+0.027HA+0.053LN+0.085PIIINP-0.016CIV。诊断的灵敏度、特异度、阳性预测价值和阴性预测价值分别为28.57%、54.76%、38.71%和43.4%。与治疗前比较,两组患者血清HA水平显著降低(P<0.01);血清CIV、LN水平明显降低(P<0.05);血清PIIINP差异无统计学意义(P>0.05)。观察组治疗后两组患者HA、PIIINP、CIV、LN水平与对照组治疗后比较,差异有统计学意义(P<0.05)。结论:血清HA、PIIINP、CIV、LN、脾脏厚度指标联合检测可提高临床诊断的准确性和可靠性。西医保肝驱铜治疗的同时,辨证使用补肾活血化浊方加减可有效改善肝功能,发挥抗纤维化作用。

Objective:To investigate the significance of serum hyaluronidase(HA),typeⅢprocollagen(PIIINP),typeⅣcollagen(CIV),laminin(LN)and related liver function indexes in the diagnosis of hepatolenticular degeneration and the clinical effect of Bushen Huoxue Huazhuo Decoction in the treatment of hepatolenticular degeneration(HLD).Methods:42 patients with HLD were randomly divided into the control group and the observation group,with 21 cases in each group.The control group was treated with Glutathione and Sodium Dimercaptopropylsulfonate(DMPS)to protect liver and expel copper;on which basis,the observation group was also treated with modified Bushen Huoxue Huazhuo Decoction.Both groups were treated for four courses,with 8 days were taken as one course.The serum levels of HA,PIIINP,CIV,LN and AKP,as well as related liver function indexes were measured in 42 patients with HLD and in 42 normal people.42 patients with HLD underwent acoustic radiation force impulse(ARFI)and conventional ultrasound to observe the degree of liver fibrosis and spleen thickness,thus to carry out a comparative study of liver fibrosis.Results:The levels of HA,PIIINP,CIV and LN in HLD patients were significantly higher than those in the normal people(P<0.01).The levels of HA,PIIINP,CIV,LN and spleen thickness were highly positively correlated with fibrosis stage(r=0.849,0.858,0.677,0.903,0.933,P<0.05).The discriminant function of combined diagnosis of four indexes was-12.268+0.027 HA+0.053 LN+0.085 PIIINP-0.016 CIV.The sensitivity,specificity,positive predictive value and negative predictive value were 28.57%,54.76%,38.71%and 43.4%respectively.Compared to those before the treatment,the levels of serum HA,CIV and LN were significantly lowered after the treatment in the two groups(P<0.05,P<0.01);however,there was no statistical difference in the serum level of PIIINP between before and after the treatment in the two groups(P>0.05).There were statistical differences in the levels of HA,PIIINP,CIV and LN after the treatment between the observation group and the control group(P<0.05).Conclusion:The combined detection of serum HA,PIIINP,CIV,LN and spleen thickness can improve the accuracy and reliability of clinical diagnosis.Modified Bushen Huoxue Huazhuo Formula can effectively improve liver function and play an anti-fibrosis role on the basis of western medical treatment of protecting liver and expelling copper.