慢性肝病合并自身免疫性血液系统疾病的临床特征及应用糖皮质激素治疗效果分析

刘龙; 刘遥; 高方媛; 王宪波

doi:10.3969/j.issn.1001-5256.2021.08.025

慢性肝病合并自身免疫性血液系统疾病的临床特征及应用糖皮质激素治疗效果分析

DOI: 10.3969/j.issn.1001-5256.2021.08.025

首都医科大学附属北京地坛医院中西医结合中心, 北京 100015

基金项目:

首都卫生发展科研专项项目 (2018-1-2172);

北京市科学技术委员会资助 (Z191100006619033)

利益冲突声明: 本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明: 刘龙负责数据采集、研究设计及文章撰写; 刘遥、高方媛参与数据分析过程及修改文章关键内容; 王宪波对研究的设计及实施给予指导与支持。

详细信息

通信作者:
王宪波, wangxianbo638@163.com

中图分类号: R575
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出版历程
- 收稿日期: 2021-03-04
- 录用日期: 2021-05-14
- 出版日期: 2021-08-20

Clinical features of chronic liver disease with autoimmune blood diseases and the clinical effect of glucocorticoid

Department of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

Research funding:

Capital's Funds for Health Improvement and Research (2018-1-2172);

Funded by Beijing Science and Technology Committee (Z191100006619033)

摘要

摘要: 目的分析慢性肝病合并免疫性血液系统疾病的临床特征, 探究糖皮质激素的疗效。方法回顾性分析2008年1月—2019年12月北京地坛医院收治的17例慢性肝病合并免疫性血液病患者的临床资料, 根据血液病种类分为3组: 自身免疫性溶血性贫血(AIHA)组、免疫性血小板减少症(ITP)组、Evans综合征组。进行糖皮质激素治疗及肝病相关治疗后, 比较3组治疗前后临床资料及实验室检查指标。计量资料两组间比较采用Mann-Whitney U检验。结果 17例慢性肝病患者中有15例非病毒性肝炎患者, 其中自身免疫性肝病9例(占52.9%)。17例患者血液系统疾病分布: AIHA患者6例, ITP患者8例, Evans综合征患者3例。其中13例患者进行糖皮质激素治疗, 达到完全缓解或部分缓解者共12例, 总有效率92.3%。ITP组TBil、DBil治疗后较治疗前显著下降[35.8(14.3~58.0)μmol/L vs 165.6(21.3~374.3)μmol/L, Z=-2.205, P=0.027;24.9(7.0~43.3)μmol/L vs 121.9(11.7~279.9)μmol/L, Z=-2.205, P=0.027];AIHA组血红蛋白治疗后较治疗前显著上升[94.0(65.0~99.3)g/L vs 62.2(42.3~80.5)g/L, Z=-2.242, P=0.025]。结论多种类型慢性肝病均可合并免疫性血液系统疾病, 其中自身免疫性肝病合并免疫性血液系统疾病的发病率较高; 糖皮质激素是慢性肝病合并免疫性血液系统疾病安全有效的治疗方法。
- 肝疾病 /
- 贫血, 溶血性, 自身免疫性 /
- 紫癜, 血小板减少性, 特发性 /
- Evans综合征 /
- 糖皮质激素类
Abstract: Objective To investigate the clinical features of chronic liver disease with immune blood diseases and the clinical effect of glucocorticoid therapy. Methods A retrospective analysis was performed for the clinical data of 17 patients with chronic liver disease and immune blood diseases who were admitted to Beijing Ditan Hospital from January 2008 to December 2019, and according to the type of blood disease, they were divided into autoimmune hemolytic anemia (AIHA) group, immune thrombocytopenia (ITP) group, and Evans syndrome group. After glucocorticoid therapy and related treatment of liver disease, the three groups were compared in terms of clinical data and laboratory markers before and after treatment. The Mann-Whitney U test was used for comparison of continuous data between two groups. Results Among the 17 patients with chronic liver disease, 15 had no viral hepatitis, among whom 9 (52.9%) had autoimmune liver disease. Among these 17 patients, 6 had AIHA, 8 had ITP, and 3 had Evans syndrome. Glucocorticoid therapy was given for 13 patients, among whom12 achieved complete remission or partial remission, resulting in an overall response rate of 92.3%. After treatment, the ITP group had significant reductions in total bilirubin [35.8 (14.3-58.0) μmol/L vs 165.6 (21.3-374.3) μmol/L, Z=-2.205, P=0.027] and direct bilirubin [24.9 (7.0-43.3) μmol/L vs 121.9 (11.7-279.9) μmol/L, Z=-2.205, P=0.027], and the AIHA group had a significant increase in hemoglobin [94.0 (65.0-99.3) g/L vs 62.2 (42.3-80.5) g/L, Z=-2.242, P=0.025]. Conclusion Immune blood diseases are observed in patients with various types of chronic liver disease, among which autoimmune liver disease with immune blood diseases has a relatively high incidence rate. Glucocorticoid is a safe and effective therapeutic method for the treatment of chronic liver disease with immune blood diseases.
- Liver Diseases /
- Anemia, Hemolytic, Autoimmune /
- Purpura, Thrombocytopenic, Idiopathic /
- Evans Syndrome /
- Glucocorticoids

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表 1 患者一般情况、基础肝病及合并血液病种类、发病先后次序

编号	年龄	性别	血液病种类	肝病类型	特殊诱因
1	46	女	ITP	AIH¹⁾	异常子宫出血
2	36	男	AIHA	不明原因肝硬化¹⁾	药物(CCI-779)
3	28	女	Evans综合征	狼疮性肝炎¹⁾	无
4	60	女	AIHA	AIH¹⁾	无
5	66	女	ITP	不明原因肝硬化¹⁾	无
6	39	女	ITP¹⁾	AIH	无
7	56	女	Evans综合征	PBC¹⁾	无
8	29	男	ITP¹⁾	AIH	无
9	49	女	ITP	PBC¹⁾	无
10	32	男	AIHA	酒精性肝硬化¹⁾	无
11	31	男	ITP	慢性乙型肝炎¹⁾	无
12	60	女	AIHA	AIH¹⁾	无
13	61	男	Evans综合征	PBC¹⁾	无
14	35	女	ITP¹⁾	药物性肝炎	无
15	63	女	AIHA	PBC¹⁾	无
16	63	女	AIHA	药物性肝炎¹⁾	药物(特比萘芬)
17	60	女	ITP	乙型肝炎肝硬化¹⁾	无
注: 1)首发疾病。

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表 2 ITP、AIHA及Evans综合征患者治疗前后实验室指标比较

变量	ITP (n=8)	AIHA (n=6)	Evans综合征(n=3)
WBC(10⁹/L)
治疗前	5.2(3.4~7.4)	4.5(3.2~7.2)	5.5(4.7~6.4)
治疗后	5.4(4.1~11.9)	3.8(3.6~11.9)	8.2(5.7~10.7)
Z值	-0.630	-0.160	-0.218
P值	0.529	0.873	0.827
HGB(g/L)
治疗前	95.6(63.2~122.3)	62.2(42.3~80.5)	79.0(68.1~89.9)
治疗后	97.0(60.5~143.0)	94.0(65.0~99.3)	79.1(75.2~83.0)
Z值	-1.052	-2.242	-0.655
P值	0.293	0.025	0.513
PLT(10¹²/L)
治疗前	54.0(13.8~83.1)	91.1(48.8~280.0)	46.9(28.7~68.1)
治疗后	56.3(25.1~125.0)	41.0(30.0~146.0)	45.7(10.2~76.7)
Z值	-1.470	-0.320	-0.655
P值	0.141	0.749	0.513
网织红细胞(%)
治疗前	7.0(2.9~9.5)	13.7(12.6~15.8)	10.3(7.3~16.8)
治疗后	5.8(1.5~7.8)	14.1(11.2~17.0)	—
Z值	-1.944	-0.823
P值	0.052	0.410
PT(s)
治疗前	19.7(15.0~25.7)	16.4(11.5~24.9)	12.8(10.9~13.8)
治疗后	14.7(11.1~21.6)	11.4(10.1~26.4)	13.5(10.2~16.7)
Z值	-1.470	-0.548	-0.577
P值	0.141	0.584	0.564
ALT(U/L)
治疗前	361.7(9.4~677.5)	106.6(21.1~346.9)	69.2(28.4~92.0)
治疗后	30.9(15.8~71.9)	22.0(16.7~82.5)	68.6(62.0~75.1)
Z值	-0.315	-0.365	-1.732
P值	0.753	0.715	0.083
AST (U/L)
治疗前	263.7(28.6~663.1)	101.4(32.2~237.1)	188.2(63.9~256.1)
治疗后	43.1(23.1~53.1)	43.4(19.4~58.6)	60.1(38.0~82.2)
Z值	-1.365	-0.913	-0.577
P值	0.172	0.361	0.564
TBil(μmol/L)
治疗前	165.6(21.3~374.3)	164.0(87.4~277.8)	94.0(74.3~108.3)
治疗后	35.8(14.3~58.0)	148.8(34.2~227.4)	101.5(75.3~127.8)
Z值	-2.205	-0.730	-1.155
P值	0.027	0.465	0.248
DBil(μmol/L)
治疗前	121.9(11.7~279.9)	118.4(29.8~224.4)	56.4(30.2~81.5)
治疗后	24.9(7.0~43.3)	94.4(23.8~148.9)	56.3(8.4~104.1)
Z值	-2.205	-0.548	0.000
P值	0.027	0.584	1.000
Alb(g/L)
治疗前	29.6(25.4~32.5)	32.2(27.7~36.1)	30.3(26.6~35.1)
治疗后	34.1(28.0~35.9)	33.7(29.5~46.2)	35.2(34.6~39.4)
Z值	-1.944	-0.823	-1.155
P值	0.052	0.410	0.248
肌酐(mmol/L)
治疗前	63.0(47.7~82.2)	66.4(53.8~85.2)	49.7(42.8~55.0)
治疗后	57.2(44.5~76.0)	61.4(59.8~77.6)	—
Z值	-0.630	0.000
P值	0.529	1.000
注: —, 未化验。

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参考文献(19)

[1]	SHAH AS, AMARAPURKAR DN. Spectrum of hepatitis B and renal involvement[J]. Liver Int, 2018, 38(1): 23-32. DOI: 10.1111/liv.13498.
[2]	WU R, LENG AM. Primary biliary cirrhosis with autoimmune hemolytic anemia: A case report[J]. J Clin Hepatol, 2020, 36(12): 2795-2797. DOI: 10.3969/j.issn.1001-5256.2020.12.030. 吴蓉, 冷爱民. 原发性胆汁性肝硬化合并自身免疫性溶血性贫血1例报告[J]. 临床肝胆病杂志, 2020, 36(12): 2795-2797. DOI: 10.3969/j.issn.1001-5256.2020.12.030.
[3]	Red Blood Cell Disease(Anemia) Group, Chinese Society of Hematology & Chinese Medical Association. Chinese expert consensus on the diagnosis and treatment of autoimmune hemolytic anemia(2017)[J]. China J Hematol, 2017, 38(4): 114-115. DOI: 10.3760/cma.j.issn.0253-2727.2017.04.001. 中华医学会血液病分会红细胞疾病(贫血)学组. 自身免疫性贫血诊断与治疗中国专家共识[J]. 中华血液学杂志, 2017, 38(4): 114-115. DOI: 10.3760/cma.j.issn.0253-2727.2017.04.001.
[4]	PETERMANN R. Platelet transfusion role in neonatal immune thrombocytopenia[J]. Transfus Clin Biol, 2016, 23(4): 217-221. DOI: 10.1016/j.tracli.2016.07.006.
[5]	Thrombosis and Hemostasis Group, Chinese Society of Hematology, Chinese Medical Association. Chinese guideline on the diagnosis and management of adult primary immune thrombocytopenia (2020)[J]. China J Hematol, 2020, 41(8): 617-623. DOI: 10.3760/cma.j.issn.0253-2727.2020.08.001. 中华医学会血液病分会血栓与止血学组. 成人原发免疫性血小板减少症诊断与治疗中国指南[J]. 中华血液学杂志, 2020, 41(8): 617-623. DOI: 10.3760/cma.j.issn.0253-2727.2020.08.001.
[6]	SYLVAIN A, NATACHA G, MORGANE M, et al. Evans' syndrome: From diagnosis to treatment[J]. J Clin Med, 2020, 9(12): 3851. DOI: 10.1542/peds.2010-2615.
[7]	SAAB S, BROWN RS Jr. Management of thrombocytopenia in patients with chronic liver disease[J]. Dig Dis Sci, 2019, 64(10): 2757-2768. DOI: 10.1007/s10620-019-05615-5.
[8]	FUKUDA H, TAKATA K, KITAGUCHI T, et al. Autoimmune hepatitis with concomitant idiopathic thrombocytopenic purpura diagnosed by transjugular liver biopsy[J]. Case Reports Hepatol, 2018, 2018: 5305691. DOI: 10.1155/2018/5305691.
[9]	PECK-RADOSAVLJEVIC M. Thrombocytopenia in chronic liver disease[J]. Liver Int, 2017, 37(6): 778-793. DOI: 10.1111/liv.13317.
[10]	NESCHADIM A, KOTRA LP, BRANCH DR. Small molecule phagocytosis inhibitors for immune cytopenias[J]. Autoimmun Rev, 2016, 15(8): 843-847. DOI: 10.1016/j.autrev.2016.06.004.
[11]	ITO A, YOSHIZAWA K, FUJIMORI K, et al. Autoimmune hepatitis associated with immune thrombocytopenic purpura[J]. Intern Med, 2017, 56(2): 143-147. DOI: 10.2169/internalmedicine.56.7506.
[12]	CHEN Z, ZHANG L, LIU J, et al. Analysis on expression level of PD-1 on the surface of CD4⁺T lymphocytes in peripheral blood of patients with primary immune thrombocytopenia[J]. China Med Herald, 2021, 18(1): 92-95. 陈哲, 张灵, 刘洁, 等. 原发免疫性血小板减少症患者外周血CD4⁺T淋巴细胞表面PD-1表达水平分析[J]. 中国医药导报, 2021, 18(1): 92-95.
[13]	KORKMAZ H, BUGDACI MS, TEMEL T, et al. Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome)[J]. Clin Res Hepatol Gastroenterol, 2013, 37(2): e45-e50. DOI: 10.1016/j.clinre.2012.11.001.
[14]	BIANCO C, COLUCCIO E, PRATI D, et al. Diagnosis and management of autoimmune hemolytic anemia in patients with liver and bowel disorders[J]. J Clin Med, 2021, 10(3): 423. DOI: 10.3390/jcm10030423.
[15]	ABDELA J. Current advance in thrombopoietin receptor agonists in the management of thrombocytopenia associated with chronic liver disease: Focus on avatrombopag[J]. Clin Med Insights Blood Disord, 2019, 12: 1179545X19875105. DOI: 10.1177/1179545X19875105.
[16]	SAMSON M, FRASER W, LEBOWITZ D. Treatments for primary immune thrombocytopenia: A review[J]. Cureus, 2019, 11(10): e5849. DOI: 10.7759/cureus.5849.
[17]	PECK-RADOSAVLJEVIC M. Thrombocytopenia in chronic liver disease[J]. Liver Int, 2017, 37(6): 778-793. DOI: 10.1111/liv.13317.
[18]	WANG SC, YANG KD, LIN CY, et al. Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia[J]. Pediatr Blood Cancer, 2020, 67(2): e28075. DOI: 10.1002/pbc.28075.
[19]	LEE JB, PARK HS, PARK S, et al. Temsirolimus in Asian metastatic/recurrent non-clear cell renal carcinoma[J]. Cancer Res Treat, 2019, 51(4): 1578-1588. DOI: 10.4143/crt.2018.671.