雷公藤多甙、硫唑嘌呤联合甘草酸二铵治疗自身免疫性肝炎患者初步临床研究

doi:10.3969/j.issn.1672-5069.2017.03.009

摘要/Abstract

摘要： 目的探讨雷公藤多甙片、硫唑嘌呤片联合甘草酸二铵治疗自身免疫性肝炎（AIH）患者的疗效。方法将2015年1月~2016年1月我院收治的68例AIH患者随机分为对照组和观察组,每组34例。给予对照组患者硫唑嘌呤片联合甘草酸二铵治疗,观察组在对照组治疗的基础上接受雷公藤多甙片治疗3个月,观察两组治疗前后血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）和总胆红素（TBIL）、血清免疫球蛋白IgG、IgA和IgM以及肝纤维化指标透明质酸（HA）和层粘蛋白（LN）的变化,观察两组治疗期间不良反应事件发生情况。结果在治疗3个月末,观察组患者血清ALT、AST、ALP和TBIL水平分别为（51.7±7.2） U/L、（45.6±8.1） U/L、（67.4±3.2） U/L和（11.4±1.2） μmol/L,显著低于对照组[分别为（79.7±11.9） U/L、（77.1±9.2） U/L、（87.1±4.0） U/L和（15.3±1.4） μmol/L,P<0.05];观察组血IgG、IgA和IgM水平分别为（11.29±2.24） mg/ml、（2171.4±100.3） mg/L和（2218.8±98.2） mg/L,均显著低于对照组[分别为（14.80±2.75） mg/ml、（2839.9±107.0） mg/L和（2912.0±113.1） mg/L,P<0.05];观察组血清HA、LN和PCⅢ水平分别为（112.4±6.8）μg/L、（61.3±4.6）μg/L和（52.4±3.3）μg/L,均较对照组显著降低[（164.2±7.3）μg/L、（82.6±5.7）μg/L和（79.2±4.4）μg/L,P<0.05];在治疗期间两组均未出现严重不良反应。结论雷公藤多甙片、硫唑嘌呤片联合甘草酸二铵治疗AIH患者临床疗效优于硫唑嘌呤片联合甘草酸二铵治疗者。

关键词: 自身免疫性肝炎, 雷公藤多甙片, 硫唑嘌呤片, 甘草酸二铵, 治疗

Abstract: Objective To explore the effect of tripterygium glycosides,azathioprine combined with diammonium glycyrrhizinate in the treatment of patients with autoimmune hepatitis（AIH）. Methods 68 patients with AIH were recruited in our hospital between January 2015 and January 2016,and the patients were randomly divided into control and observation group with 34 cases in each. The patients in the control group were treated with azathioprine and diammonium glycyrrhizinate,and the patients in the observation group were given tripterygium glycosides,azathioprine combined with diammonium glycyrrhizinate for 3 months. Before and after treatment,serum ALT,AST,ALP and TBIL,serum immunoglobulin and hepatic fibrosis index （HA,LN and PC III） levels were detected. Results At the end of 3 months treatment,serum ALT,AST,ALP and TBIL levels in the observation group were（51.7±7.2） U/L,（45.6±8.1） U/L,（67.4±3.2） U/L and（11.4±1.2） μmol/L,respectively, significantly lower than those in the control group [（79.7±11.9） U/L,（77.1±9.2） U/L,（87.1±4.0） U/L and （15.3±1.4） μmol/L,P<0.05];serum IgG,IgA and IgM levels in the observation group were （11.29±2.24） mg/ml,（2171.4±100.3） mg/L and（2218.8±98.2） mg/L,significantly lower than those in the control group[（14.80±2.75） mg/ml, （2839.9±107.0） mg/L and（2912.0±113.1） mg/L,P<0.05];and serum levels of HA,LN and PCⅢ were （112.4±6.8） μg/L,（61.3±4.6） μg/L and（52.4±3.3） μg/L,significantly lower than those in the control group [（164.2±7.3） μg/L,（82.6±5.7） μg/L and（79.2±4.4） μg/L,P<0.05];No serious adverse reaction was observed in the two groups. Conclusion Azathioprine,diammonium glycyrrhizinate,and tripterygium glycosides therapy have a better efficacy in patients with AIH in the short-term observation.

Key words: Autoimmune hepatitis, Tripterygium glycosides, Azathioprine, Diammonium glycyrrhizinate, Therapy

尚瑞, 吴军. 雷公藤多甙、硫唑嘌呤联合甘草酸二铵治疗自身免疫性肝炎患者初步临床研究[J]. 实用肝脏病杂志, 2017, 20(3): 290-293.

Shang Rui, Wu Jun. Effect of tripterygium glycosides and azathioprine combined with diammonium glycyrrhizinate in the treatment of patients with autoimmune hepatitis[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(3): 290-293.

参考文献

[1] Murunga E,Andersson M,Rensburg CV. Autoimmune hepatitis:a manifestation of immune reconstitution inflammatory syndrome in HIV infected patients Scand J Gastroenterol,2016,51(7):814-818.
[2] Czaja AJ.Transitioning from idiopathic to explainable autoimmune hepatitis. Dig Dis Sci,2015,60(10):2881-2900.
[3] Littera R,Chessa L,Onali S,et al.Exploring the role of killer cell immunoglobulin-like receptors and their HLA class I ligands in Autoimmune hepatitis. PLoS One,2016,11(1):e0146086.
[4] Canivet CM,Anty R,Patouraux S,et al.Immunoglobulin G4-associated autoimmune hepatitis may be found in western countries. Dig Liver Dis,2016,48(3):302-308.
[5] He R,Wang L,Zhu J,et al.Methane-rich saline protects against concanavalin A-induced autoimmune hepatitis in mice through anti-inflammatory and anti-oxidative pathways. Biochem Biophys Res Commun,2016,470(1):22-28.
[6] Battagliotti C,Rispolo Klubek D,Karakachoff M,et al.An overlap syndrome involving systemic lupus erythematosus and autoimmune hepatitis in an adolescent girl. Arch Argent Pediatr,2016,114(3):e155-e158.
[7] 朱常江,吴镇印,叶映月,等. 中西医结合治疗自身免疫性肝炎的临床观察. 中国中医急症,2015,24(1):173-175.
[8] 姚骥如,孙莹,罗顺葵. 雷公藤多苷的临床应用进展. 中国新药与临床杂志,2010,29(3):179-182.
[9] 王绮夏,邱德凯,马雄. 2010年美国肝病学会自身免疫性肝炎指南解读. 中国肝脏病杂志(电子版),2011,3(3):23-28.
[10] Gatselis NK,Zachou K,Koukoulis GK,et al.Autoimmune hepatitis,one disease with many faces:etiopathogenetic,clinico-laboratory and histological characteristics. World J Gastroenterol,2015,21(1):60-83.
[11] 艾月梅,严玉娟,邢益平. 自身免疫性肝病临床诊治研究进展. 实用肝脏病杂志,2016,19(3):360-364.
[12] Gronbaek L,Vilstrup H,Jepsen P,et al.Autoimmune hepatitis in Denmark:incidence,prevalence,prognosis,and causes of death. A nationwide registry-based cohort study. J Hepatol,2013,60: 612-617.
[13] Than NN,Wiegard C,Weiler-Normann C,et al.Long-term follow-up of patients with difficult to treat type 1 autoimmune hepatitis on tacrolimus therapy. Scand J Gastroenterol,2016,51(3):329-336.
[14] Manns MP,Lohse AW,Vergani D.Autoimmune hepatitis update-2015. J Hepatol,2015,62(Suppl 1):S100-S111.
[15] Buijs J,van Heerde MJ,Rauws EA,et al. Comparable efficacy of low- versus high-dose induction corticosteroid treatment in autoimmune pancreatitis. Pancreas,2014,43: 261-267.
[16] Gardner CS,Bashir MR,Marin D,et al.Diagnostic performance of imaging criteria for distinguishing autoimmune cholangiopathy from primary sclerosing cholangitis and bile duct malignancy. Abdom Imaging,2015,40(8):3052-3061.
[17] Tokala A,Khalili K,Menezes R,et al.Comparative MRI analysis of morphologic patterns of bile duct disease in IgG4-related systemic disease versus primary sclerosing cholangitis. AJR,2014,202:536-543.
[18] Ozaslan E,Efe C,Heurgué-Berlot A,et al.Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis. Clin Gastroenterol Hepatol,2014,12(5):863-869.
[19] Zhu GQ,Shi KQ,Huang GQ,et al.A network meta-analysis of the efficacy and side effects of udca-based therapies for primary sclerosing cholangitis. Oncotarget,2015,6(29): 26757-26669.
[20] Wunsch E,Trottier J,Milkiewicz M,et al.Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis. Hepatology,2014,60(3):931-940.
[21] Parker R,Oo YH,Adams DH.Management of patients with difficult autoimmune hepatitis. Therap Adv Gastroenterol,2012,5(6):421-437.
[22] Metzger J,Negm AA,Plentz RR,et al.Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders. Gut,2013,62(1):122-130.
[23] Poonja Z,Briesbois A,Zanten SV,et al.Patients with cirrhosis and denied liver transplants rarely receive adequate palliative care or appropriate management. Clin Gastroenterol Hepatol,2014,12:692-698.
[24] Puche JE,Saiman Y,Friedman SL.Hepatic stellate cells and liver fibrosis. Compr Physiol,2013,3:1473-1492.
[25] Ushijima Y,Tajima T,Yoshimitsu K,et al.Radiological catheter placement for transcatheter arterial steroid injection therapy to treat severe acute hepatic failure:technical feasibility and efficacy. Acta Radiologica,2012,53(2):140-146.