门窦血管性疾病的临床特征与中药用药特点探讨

李盟; 郭亚楠; 邢枫; 吕靖; 刘成海

doi:10.3969/j.issn.1671-038X.2024.12.08

门窦血管性疾病的临床特征与中药用药特点探讨

- 1.
  上海中医药大学附属曙光医院肝病研究所(上海，201203)
- 2.
  河南中医药大学第二附属医院肝胆脾胃科
- 3.
  上海市中医临床重点实验室与肝肾疾病病证教育部重点实验室
- 4.
  上海中医药大学附属曙光医院肝病科
基金项目:
国家自然科学基金项目(No：82274305)；上海市临床重点专科建设项目(No：shslczdzk01201)

详细信息

通讯作者: 刘成海，E-mail：chenghailiu@hotmail.com

中图分类号: R575

收稿日期: 2024-10-23

刊出日期: 2024-12-15

The clinical characteristics of patients with porto-sinusoidal vascular disorder and applications of traditional Chinese medicine

- 1.
  Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
- 2.
  Department of Hepatobiliary Spleen and Stomach, the Second Affiliated Hospital of Henan University of Chinese Medicine
- 3.
  Shanghai Key Laboratory of Clinical Traditional Chinese Medicine and the Ministry of Education Key Laboratory for Diseases and Syndromes of Liver and Kidney
- 4.
  Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

More Information

Corresponding author: LIU Chenghai, E-mail: chenghailiu@hotmail.com

Received Date: 23 October 2024

Publish Date: 15 December 2024

摘要

摘要: 目的探讨门窦血管性疾病(porto-sinusoidal vascular disorder，PSVD)患者的临床特点及其中医药治法用药经验。方法回顾性收集2016年1月—2023年12月于我院经肝穿刺活检确诊的PSVD患者的临床资料、血清学及影像学检查资料。根据是否具有特征性门静脉高压表现分为门静脉高压组与非门静脉高压组，比较2组PSVD患者的临床特点、病理特征，并统计分析病情稳定或好转的随访患者的中医处方信息。结果共收集47例患者，其肝功能、肾功能、凝血功能基本在正常范围，60%的患者血小板计数明显低于150×10⁹/L，60%的患者伴有肝脏相关慢性疾病，临床表现以脾大最常见(89.36%)，病理学表现以汇管区异常最常见(80.85%)。以是否具有特征性门静脉高压分层统计发现，门静脉高压组红细胞计数、血红蛋白、白蛋白显著减少，而D-二聚体显著升高，肝组织非带状肝窦扩张的比例显著增加、闭塞性门静脉病变累及汇管区更多。中医处方信息分析提示，黄芪、白术、党参等健脾益气与丹参、赤芍、当归等活血化瘀药物是2组PSVD的共性治法药物；非门静脉高压组重在益气健脾与活血化瘀，而门静脉高压组重在健脾补肾与活血破瘀。结论 PSVD可常见于病因明确的慢性肝病患者，以血小板减少、脾大、肝组织汇管区异常最为多见；伴有门静脉高压患者的肝组织闭塞性门静脉病变更严重、肝组织非带状肝窦扩张比例更高，中医治疗以益气健脾、活血化瘀为主要治法，门静脉高压患者可加用补益肝肾与破血逐瘀之品。
- 门窦血管性疾病 /
- 门静脉高压 /
- 中药 /
- 活血化瘀 /
- 用药特点
Abstract: Objective To investigate the clinical characteristics and treatment with traditional Chinese medicine(TCM) for patients with porto-sinusoidal vascular disorder(PSVD). Methods We retrospectively observed patients with PSVD diagnosed by liver biopsy at our hospital between January 2016 and December 2023, collected their data including clinical manifestations, serological and image findings at the time of liver biopsy. Patients were divided into two groups: portal hypertension(PH) and non-PH group. The clinical features, pathological characteristics and TCM applications in PSVD patients were analyzed, and the differences between PH and non-PH subgroups in PSVD were compared. Results A total of 47 patients were included in the study. Their liver function, renal function, and coagulation function were within normal ranges. However, 60% of the patients had lower level of platelet counts than 150×10⁹/L. 60% of the patients had chronic liver diseases, and the most common clinical manifestation was splenomegaly(89.36%). Histopathologically, periportal abnormalities were most frequently observed(80.85%). Stratified analysis based on the portal hypertension revealed that the PH group had significantly lower red blood cell counts, hemoglobin levels, and albumin levels, while D-dimer levels were significantly elevated. The proportion of hepatic non-zonal sinusoidal dilatation(NSD) and obliterative portal venopathy(OPV) were higher in the PH group. TCM prescription analysis indicated that the spleen-strengthening and qi-invigorating herbs such as Astragalus, Atractylodes, Codonopsis, and blood-activating and stasis-resolving herbs including Salvia miltiorrhiza, Paeonia rubra, Angelica sinensis were frequently used. But PSVD patients with non-PH took more herbs with qi tonification and spleen strengthening along with activating circulation, ones with PH took more herbs with spleen and kidney tonification and dissipating blood stasis. Conclusion PVSD is commonly coexisted in patients of chronic liver diseases with identified etiologies, characterized by thrombocytopenia, splenomegaly, and periportal abnormalities in liver tissue. PSVD patients with PH have more severe OPV and a higher proportion of NSD. TCM treatment primarily involves qi tonification and spleen strengthening along with activating circulation. As for PSVD with PH, additional use of herbs with functions of tonifying liver and kidney and activating blood stasis may be beneficial.
- porto-sinusoidal vascular disorder /
- portal hypertension /
- traditional Chinese medicine /
- blood-activating and stasis-resolving /
- medication usage characteristics

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图 1 PSVD患者的典型病理表现

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图 2 高频中药聚类分析谱系图

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表 1 PSVD的临床与病理特征

项目	临床表现	组织病理学表现
特征性	食管、胃或异位静脉曲张	门静脉闭塞(OPV)
	门静脉高压性出血	结节性再生性增生(NRH)
	门体侧支循环	不完全间隔纤维化(ISC)
非特征性	腹水	门管区异常(PTA)
	血小板计数＜150×10⁹/L	门静脉和中央静脉分布不规则(AC)
	脾脏最长径≥13 cm	非带状肝窦扩张(NSD)
	轻度窦周纤维化(PF)

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表 2 PSVD患者的一般资料例(%)，M(Q₁，Q₃)

一般资料	结果	参考值
男性	30(63.83)
年龄/岁	47(35.5，55.5)
RBC/(×10¹²/L)	4.65(4.20，5.08)	3.69~9.16
Hb/(g/L)	141.00(120.00，156.00)	113~151
WBC/(×10⁹/L)	4.40(3.28，5.59)	3.68~5.13
PLT/(×10⁹/L)	127.00(68.50，159.00)	110~320
ALT/(IU/L)	28.00(15.50，49.50)	7~40
AST/(IU/L)	29.00(20.50，41.00)	13~35
TBil/(μmol/L)	16.10(13.10，25.50)	0~23
ALP/(U/L)	72.00(66.50，95.00)	50~135
GGT/(U/L)	38.00(20.93，52.67)	7~45
Alb/(g/L)	42.30(38.20，44.55)	35~50
Cr/(mmol/L)	66.18(58.47，78.96)	44~97
BUN/(mmol/L)	5.18(4.30，6.18)	2.1~7.9
PT/s	12.70(12.00，13.70)	10.4~12.7
INR	1.04(1.00，1.13)	0.85~1.15
D-D/(μg/mL)	0.17(0，0.32)	＜0.5
伴随基础疾病
慢性肝脏疾病
慢性乙型病毒性肝炎	18(38.30)
药物性肝损害	6(12.77)
脂肪肝	4(8.51)
酒精性肝病	2(4.26)
自身免疫性肝炎	1(2.13)
全身免疫性疾病
类风湿性关节炎	3(6.38)
银屑病	2(4.26)
血液系统疾病
POEMS综合征	1(2.13)
真性红细胞增多症	1(2.13)
其他慢性病
高血压病	7(14.89)
糖尿病	2(4.26)

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表 3 PSVD患者的临床及组织病理学PH相关特征表现

项目		表现	例(%)
临床表现	特征性	食管、胃或异位静脉曲张	20(42.55)
	(24例)	门静脉高压性出血	4(8.51)
		门体侧支循环	8(17.02)
	非特征性	腹水	7(14.89)
	(45例)	PLT＜150×10⁹/L	32(68.09)
		脾脏最长径≥13 cm	42(89.36)
组织病理	特征性	OPV	14(29.79)
学表现	(26例)	NRH	5(10.64)
		ISC	13(27.66)
	非特征性	PTA	38(80.85)
	(41例)	AC	1(2.13)
		NSD	22(46.81)
		PF	6(12.77)

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表 4 不同程度PSVD患者的一般资料与组织学特征比较例(%)，M(Q₁，Q₃)，X±S

资料	non-PH组(23例)	PH组(24例)	统计值	P
年龄/岁	46.61±12.04	46.75±12.39	-0.04	0.97
性别			-1.99	0.04
男	18(78.26)	12(50.00)
女	5(21.74)	12(50.00)
RBC/(×10¹²/L)	4.71(4.42，5.21)	4.32(3.97，4.77)	-2.54	0.01
Hb/(g/L)	147.17±17.15	125.17±30.32	3.05	＜0.01
WBC/(×10⁹/L)	4.62(4.00，6.21)	4.02(2.04，4.70)	-1.81	0.07
PLT/(×10⁹/L)	128.00(93.00，148.00)	81.50(53.75，183.25)	-1.30	0.19
ALT/(IU/L)	34.00(19.00，48.00)	27.00(14.00，49.00)	-0.87	0.38
AST/(IU/L)	28.00(23.00，33.00)	28.50(18.25，41.00)	-0.04	0.97
TBil/(μmol/L)	16.10(11.90，22.40)	17.85(13.90，27.78)	-1.48	0.14
ALP/(U/L)	77.00(58.00，95.00)	72.00(68.25，97.50)	-0.68	0.50
GGT/(U/L)	37.00(22.00，48.00)	44.00(20.89，57.13)	-1.09	0.28
Alb/(g/L)	43.34±3.42	39.56±4.83	3.06	＜0.01
Cr/(mmol/L)	73.02±12.59	70.99±16.40	0.47	0.64
BUN/(mmol/L)	5.30(4.55，6.80)	5.00(3.85，6.00)	-1.27	0.21
PT/s	12.70(11.80，13.30)	12.70(12.20，14.23)	-0.96	0.34
INR	1.02(0.99，1.08)	1.10(1.01，1.20)	-1.88	0.06
D-D/(μg/mL)	0.14(0.09，0.32)	0.28(0.21，0.44)	-2.66	＜0.01
组织学表现
OPV	7(30.43)	7(29.17)	0.01	0.92
＜1/3	5(71.42)	1(14.29)	-2.05	0.04
1/3~2/3	1(14.29)	2(28.57)
>2/3	1(14.29)	4(57.14)
NRH	2(8.70)	3(12.50)	＜0.01	1.00
ISC	7(30.43)	6(25.00)	0.17	0.68
PTA	19(82.61)	19(79.17)	＜0.01	1.00
AC	1(4.35)	0	-	0.49
NSD	7(30.43)	15(62.50)	4.85	0.03
PF	3(13.04)	3(12.50)	＜0.01	1.00
注：＜1/3、1/3~2/3、>2/3指OPV病变汇管区占汇管区总数的比例。

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表 5 患者高频中药功效分类分析

功效分类	non-PH组			PH组
功效分类	包涵药物	频次	频率/%	包涵药物	频次	频率/%
补益药	黄芪、白术、甘草、石斛、党参、地黄、太子参	90	31.69	黄芪、白术、女贞子、巴戟天、党参、麦冬	91	33.21
理血药	丹参、赤芍、当归、郁金、桃仁	59	20.77	水蛭、丹参、当归、赤芍、郁金、川芎	60	21.90
清热祛湿药	黄芩、苍术、茯苓、薏苡仁	55	19.37	苍术、茯苓、薏苡仁、金钱草、黄芩	66	24.08
理气消食药	陈皮、鸡内金	38	13.38	陈皮、枳壳、鸡内金	35	9.85

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