熊去氧胆酸治疗慢性药物性肝病疗效分析

Retrospective clinical analysis of the treatment efficacy of ursodeoxycholic acid in chronic drug-induced liver injury

目的观察熊去氧胆酸治疗药物性肝病的临床疗效,对慢性药物性肝病的治愈率的影响,分析慢性药物性肝炎的病理组织学特点。方法回顾性分析了49例慢性药物性肝病患者,治疗组给予熊去氧胆酸联合常规保肝降酶药物,对照组给予常规保肝降酶药物治疗,治疗3个月和6个月后,观察两方案治疗后肝功能指标的变化、临床疗效,随访至6个月分析慢性药物性肝炎的治愈率并对治疗无效病例行肝脏穿刺及病理组织学检查。结果治疗3个月和6个月时,治疗组患者血清总胆红素(TBil)均值分别为56.17μmol/L和19.42μmol/L、碱性磷酸酶(ALP)均值分别为129.64 U/L和72.79 U/L、γ-谷酰转肽酶(GGT)均值分别为101 U/L和71 U/L,均较对照组明显下降(P<0.05),ALT在两组患者中均有大幅度下降,但差异无统计学意义(P>0.05),治疗3个月时治疗组的显效率(34.8%)和有效率(47.8%)均优于对照组(P<0.05),治疗6个月时显效率(69.7%)和有效率(21.7%)治疗组无明显差异(P>0.05),随访至6个月时发现治疗组慢性药物性肝炎的无效率(8.7%)明显低于对照组的(23.1%)(P<0.05),两组病例经熊去氧胆酸治疗后无效的慢性药物性肝炎病理组织学改变有所不同,治疗组以汇管区炎症伴肝细胞脂肪变为主,而对照组呈现汇管区小胆管增生、肝细胞脂肪变、肝细胞内胆汁淤积等多样化表现。结论熊去氧胆酸可以有效降低慢性药物性肝病患者的ALT、TBil、GGT、ALP水平,从而改善患者的肝细胞炎症及胆汁淤积,并能提高慢性药物性肝炎的治愈率,延缓慢性药物性肝炎病理组织学进展。

Objective To investigate the treatment efficacy of ursodeoxycholic acid（UDCA）in chronic drug-induced liver injury（DILI）and its histopathology characteristics.Methods In the retrospective analysis,49 cases were divided into treatment group who received UDCA（750 mg/d）combined with basic therapy,and control group who received only the basic therapy.Therapeutic efficacy and liver function indicators were observed at month3 and 6.Cure rates in the 2 groups were evaluated at month6,and liver biopsies were conducted in patients who failed to response to the therapy for evaluating the histopathology progress.Results In treatment group,mean levels of total bilirubin（TBil）,alkaline phosphatase（ALP）,and gamma-glutamyl transpeptidase（GGT）were 56.17μmol/L and 19.42μmol/L,129.64 U/L and 72.79 U/L,101 U/L and 71 U/L at month3 and 6,respectively,which were significantly lower than that in control group（P〈0.05）.However,alanine aminotransferase（ALT）level showed no significantly difference between the 2 groups（P〉0.05）.Treatment group showed significantly higher therapeutic efficacy than control group at month 3（P〈0.05）,but not at month 6（P〉0.05）.Nevertheless,the non-response rate in treatment group（8.7%）was obviously lower than that in control group at month 6（23.1%）（P〈0.05）.The histopathology appeared to be portal area inflammation accompanied with hepatocyte adipose degeneration in treatment group,while portal bile duct hyperplasia,hepatic steatosis and hepatocyte cholestasis in control group.Conclusion UDCA could effectively improve liver function and reduce inflammation and cholestasis in patients with chronic DILI,and then increases the cure rate and postpones the histopathology progress of liver tissue.