基于倾向性评分匹配分析门静脉血栓对肝硬化患者预后的影响

肖春桃; 李贤秋; 甘佩灵; 潘潇; 周贤

doi:10.3969/j.issn.1001-5256.2021.08.017

基于倾向性评分匹配分析门静脉血栓对肝硬化患者预后的影响

DOI: 10.3969/j.issn.1001-5256.2021.08.017

西南医科大学附属医院消化内科，四川泸州 646000

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：肖春桃负责课题设计，资料分析，撰写论文；肖春桃、李贤秋、甘佩灵、潘潇负责收集及分析数据；周贤负责指导撰写并修改文章。

详细信息

通信作者:
周贤，853023378@qq.com

中图分类号: R575.2
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出版历程
- 收稿日期: 2020-12-18
- 录用日期: 2021-01-19
- 出版日期: 2021-08-20

Influence of portal vein thrombosis on the prognosis of patients with liver cirrhosis based on propensity score matching

Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China

摘要

摘要: 目的分析门静脉血栓(PVT)对肝硬化患者短期预后的影响并探讨肝硬化患者预后的危险因素。方法回顾性分析西南医科大学附属医院2018年9月—2020年3月的肝硬化住院患者临床资料，其中合并PVT患者58例为PVT组，随机选取同期无PVT患者116例为非PVT组，通过1∶ 1倾向性评分匹配(PSM)均衡组间协变量获取PVT组及非PVT组各44例。满足正态性计量资料2组间比较采用t检验，非正态性计量资料2组间比较采用Mann-Whitney U秩和检验；计数资料2组间比较采用χ²检验和Fisher确切概率法。利用Kaplan-Meier法及log-rank法分析PSM前后2组患者的生存情况及出血情况，并使用Cox风险模型分析PSM前后影响肝硬化患者预后的危险因素。结果 PSM前非PVT组患者总体生存率明显高于PVT组(P=0.008)，而PSM后2组患者总体生存率无明显差异(P=0.076)。PSM前非PVT组上消化道出血或再出血率明显低于PVT组(P＜0.001)，PSM后结果与PSM前一致(P=0.028)。PSM前肝硬化患者预后多因素分析显示，PVT(HR=2.944, 95%CI：1.364~6.441，P=0.007)和MELD评分≥15(HR=3.531，95%CI：1.630~7.650，P=0.001)是肝硬化患者短期死亡的危险因素。PSM后肝硬化患者预后多因素分析显示，MELD评分≥15是肝硬化患者短期死亡的危险因素(HR=3.312, 95%CI：1.049~10.457，P=0.041)。结论肝硬化合并PVT增加上消化道出血或再出血风险，但其不是肝硬化患者短期死亡的独立危险因素，MELD评分≥15是肝硬化患者短期死亡的独立危险因素。
- 肝硬化 /
- 门静脉 /
- 静脉血栓形成 /
- 倾向性评分 /
- 预后 /
- 危险因素
Abstract: Objective To investigate the influence of portal vein thrombosis (PVT) on the short-term prognosis of patients with liver cirrhosis and the risk factors for the prognosis of patients with liver cirrhosis. Methods A retrospective analysis was performed for the clinical data of the patients with liver cirrhosis who were hospitalized in our hospital from September 2018 to March 2020, among whom 58 patients with PVT were enrolled as PVT group and 116 patients without PVT were enrolled as non-PVT group, and 44 patients were selected from each group based on propensity score matching (PSM) at a ratio of 1∶ 1 to balance the covariates between groups. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. The Kaplan-Meier method and the log-rank method were used to analyze survival status and bleeding before and after PSM, and the Cox risk model was used to analyze the risk factors for the prognosis of patients with liver cirrhosis. Results Before PSM, the non-PVT group had a significantly higher overall survival rate than the PVT group (P=0.008), while after PSM, there was no significant difference in overall survival rate between the two groups (P=0.076). Before PSM, the non-PVT group had significantly lower incidence rates of upper gastrointestinal bleeding or rebleeding than the PVT group before and after PSM (P < 0.001), and the results after PSM were consistent with those before PSM (P=0.028). The multivariate analysis of the prognosis of the patients with liver cirrhosis before PSM showed that PVT (hazard ratio [HR]=2.944, 95% confidence interval [CI]: 1.364-6.441, P=0.007) and Model for End-Stage Liver Disease (MELD) score ≥15 (HR=3.531, 95% CI: 1.630-7.650, P=0.001) were risk factors for short-term death of the patients with liver cirrhosis, and the multivariate analysis after PSM showed that MELD score ≥15 (HR=3.312, 95% CI: 1.049-10.457, P=0.041) was a risk factor for short-term death of the patients with liver cirrhosis. Conclusion Liver cirrhosis with PVT increases the risk of upper gastrointestinal bleeding or rebleeding, but it is not an independent risk factor for short-term death in patients with liver cirrhosis. MELD score ≥15 is an independent risk factor for short-term death in patients with liver cirrhosis.
- Liver Cirrhosis /
- Portal Vein /
- Venous Thrombosis /
- Propensity Score /
- Prognosis /
- Risk Factors

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图 1 PVT组与非PVT组患者的总体生存曲线

注：a, PSM前；b，PSM后。

下载: 全尺寸图片幻灯片

图 2 PVT与非PVT患者上消化道出血或再出血发生率比较

注：a, PSM前；b，PSM后。

下载: 全尺寸图片幻灯片

图 3 MELD评分＜15与MELD评分≥15患者的总体生存率比较

注：a, PSM前；b，PSM后。

下载: 全尺寸图片幻灯片

表 1 PSM前后2组患者基线特征比较

变量	匹配前				匹配后
变量	PVT组(n=58)	非PVT组( n=116)	统计值	P值	PVT组(n=44)	非PVT组(n=44)	统计值	P值
性别[例(%)]			χ²=0.207	0.649			χ²=0.218	0.640
男	40(68.97)	76(65.52)			32(72.73)	30(68.18)
女	18(31.03)	40(34.48)			12(27.27)	14(31.82)
年龄(岁)	57.10±11.81	56.09±10.45	t=-0.574	0.566	56.14±12.27	56.89±10.81	t=-0.304	0.762
病因[例(%)]			χ²=1.035	0.793			χ²=0.255	0.968
病毒¹⁾	37(63.80)	71(61.21)			29(65.91)	29(65.91)
酒精	11(19.00)	18(15.52)			7(15.91)	7(15.91)
混合²⁾	3(5.17)	9(7.76)			3(6.82)	4(9.09)
其他	7(12.07)	18(15.52)			5(11.36)	4(9.09)
病程³⁾[例(%)]			χ²=16.289	0.001			χ²=4.356	0.225
≤1年	15(25.86)	54(46.55)			13(29.55)	11(25.00)
1~≤5年	19(32.76)	37(31.90)			15(34.09)	18(40.91)
5~≤10年	7(12.07)	16(13.80)			5(11.36)	10(22.73)
＞10年	17(29.31)	9(7.76)			11(25.00)	5(11.36)
吸烟史[例(%)]			χ²=0.307	0.580			χ²=0.809	0.368
有	20(34.48)	45(38.79)			17(38.64)	13(29.55)
无	38(65.52)	71(61.21)			27(61.36)	31(70.45)
糖尿病[例(%)]			χ²=0.021	0.886			χ²=0.723	0.395
有	10(17.24)	19(16.38)			6(13.64)	9(20.45)
无	48(82.76)	97(83.62)			38(86.36)	35(79.55)
高血压[例(%)]			χ²=0.244	0.622			χ²=0.000	1.000
有	8(13.79)	13(11.21)			6(13.64)	6(13.64)
无	50(86.21)	103(88.79)			38(86.36)	38(86.36)
Child-Pugh评分	8.00(7.00~9.00)	8.00(7.00~10.00)	Z=-0.183	0.855	8.07±1.97	8.23±2.13	t=-0.363	0.717
MELD评分	10.78±4.78	11.97±5.39	t=1.435	0.153	10.73±4.16	11.30±4.71	t=-0.600	0.550
WBC(×10⁹/L)	4.97(3.50~8.11)	4.76(3.33~6.81)	Z=-0.945	0.345	4.82(3.54~7.39)	5.02(3.31~7.91)	Z=-0.017	0.987
NEU-R(%)	74.90(65.03~82.55)	69.05(60.40~78.73)	Z=-2.254	0.024	72.95(64.73~81.58)	71.00(63.28~82.75)	Z=-0.225	0.882
Hb(g/L)	83.09±28.94	98.85±28.09	t=3.453	0.001	84.32±29.94	88.14±27.87	t=-0.619	0.537
PLT(×10⁹/L)	68.00(46.00~107.50)	70.00(49.25~96.75)	Z=-0.375	0.708	68.00(46.25~113.50)	64.50(48.50~88.75)	Z=-0.864	0.388
Alb(g/L)	32.44±4.75	33.00±6.16	t=0.667	0.506	32.38±4.64	31.80±6.16	t=0.051	0.618
ALT(U/L)	21.95(17.33~34.18)	34.07(19.15~55.13)	Z=-3.141	0.002	23.25(17.90~37.25)	21.50(14.98~45.33)	Z=-0.421	0.673
AST(U/L)	34.05(25.71~54.68)	53.75(28.63~86.43)	Z=-3.089	0.002	36.15(27.23~55.53)	38.15(22.40~67.88)	Z=-0.013	0.990
TBil(μmol/L)	20.95(16.27~41.08)	29.25(17.75~57.83)	Z=-2.696	0.007	21.73(17.05~44.73)	24.60(17.16~35.63)	Z=-0.396	0.692
GGT(U/L)	35.60(19.65~79.63)	49.10(23.43~99.93)	Z=-1.911	0.056	38.10(18.68~44.73)	35.10(18.58~68.76)	Z=-0.108	0.914
ALP(U/L)	85.70(62.70~126.00)	103.25(72.00~160.03)	Z=-2.233	0.025	86.75(63.38~135.20)	80.80(61.55~103.03)	Z=-0.847	0.397
SCr(μmol/L)	69.05±22.99	65.52±21.68	t=-0.992	0.323	68.94±22.61	65.83±25.68	t=0.600	0.550
Na(mmol/L)	138.77±4.96	138.74±5.67	t=-0.033	0.973	138.69±5.10	138.91±4.10	t=-0.221	0.826
BUN(μmol/L)	7.00(4.71~11.04)	6.16(4.52~7.81)	Z=-1.960	0.050	6.50(4.68~10.69)	6.60(4.52~9.27)	Z=-0.513	0.608
PT(s)	17.69±3.18	17.30±3.26	t=-0.760	0.448	17.46±3.17	17.94±3.35	t=-0.683	0.496
APTT(s)	39.20±6.84	40.18±6.36	t=0.940	0.349	39.12±6.54	39.49±6.53	t=-0.269	0.788
INR	1.35(1.26~1.57)	1.35(1.19~1.54)	Z=-1.127	0.260	1.34(1.24~1.54)	1.37(1.28~1.62)	Z=-0.847	0.397
PTA(%)	61.16±14.48	64.76±17.47	t=1.353	0.178	62.84±14.49	59.95±14.38	t=0.939	0.350
D-二聚体	2.36(1.07~5.01)	1.01(0.58~2.58)	Z=-3.853	＜0.001	2.09(0.95~4.55)	1.74(0.48~3.84)	Z=-1.006	0.315
FIB(g/L)	2.04±0.78	2.14±1.03	t=0.691	0.491	2.07±0.68	1.89±0.81	t=1.088	0.280
AT-Ⅲ	57.17±17.59	58.31±21.10	t=0.355	0.723	57.59±17.58	55.30±18.42	t=0.596	0.553
脾/胃-肾分流[例(%)]			χ²=6.092	0.014			χ²=0.090	0.764
有	12(20.69)	9(7.76)			7(15.91)	6(13.64)
无	46(79.31)	107(92.24)			37(84.09)	38(86.36)
门静脉内径(cm)	1.57(1.40~1.79)	1.40(1.30~1.50)	Z=-3.575	＜0.001	1.54±0.27	1.49±0.26	t=0.892	0.375
脾切除/栓塞史[例(%)]			χ²=0.509	0.363			χ²=0.621	0.431
有	6(10.34)	7(6.03)			5(11.36)	2(4.55)
无	52(89.66)	109(93.97)			39(88.64)	42(95.45)
硬化剂注射史[例(%)]			χ²=0.028	0.867			χ²=0.000	1.000
有	7(12.07)	12(10.34)			7(15.91)	7(15.91)
无	51(87.93)	104(89.66)			37(84.09)	37(84.09)
注：1)包括乙型及丙型病毒性肝炎；2)病毒性肝炎合并酒精性肝硬化；3)确诊肝硬化到此次住院的间隔时间。

下载: 导出CSV

表 2 PSM前后肝硬化患者预后的单因素Cox分析

变量	PSM前(n=170)				PSM后(n=85)
变量	例数	HR	95%CI	P值	例数	HR	95%CI	P值
性别(男/女)	113/57	0.921	0.417~2.036	0.839	59/26	0.686	0.217~2.169	0.521
年龄(＜65岁/≥65岁)	121/49	2.276	1.050~4.930	0.037	59/26	2.602	0.835~8.110	0.099
糖尿病(是/否)	26/144	1.042	0.359~3.028	0.939	14/71	1.298	0.283~5.966	0.737
病因
病毒	105			0.128	56			0.790
酒精	29	0.583	0.205~1.655	0.310	14	1.207	0.148~9.821	0.860
混合	11	1.699	0.554~5.208	0.354	6	2.187	0.227~21.060	0.498
其他	25	0.607	0.071~5.206	0.649	9	2.185	0.136~35.093	0.581
病程
≤1年	69			0.612	24			0.669
1~≤5年	55	0.795	0.230~2.163	0.541	32	2.099	0.218~20.235	0.521
5~≤10年	22	0.825	0.269~2.253	0.736	15	2.307	0.269~19.812	0.446
＞10年	24	1.482	0.426~5.157	0.537	14	3.953	0.408~38.283	0.236
Child分级(A~B级/C级)	129/41	3.093	1.430~6.689	0.004	66/19	2.899	0.919~9.151	0.069
MELD评分(＜15/≥15)	131/39	3.305	1.528~7.148	0.002	68/17	3.312	1.049~10.457	0.041
PVT(有/无)	54/116	2.746	1.258~5.995	0.011	41/44	3.084	0.832~11.435	0.092
PLT (＜110×10⁹/L/≥110×10⁹/L)	135/35	1.510	0.520~4.386	0.449	68/17	1.336	0.361~4.941	0.664
分流(是/否)	20/150	1.458	0.548~3.878	0.450	13/72	1.134	0.248~5.192	0.871
出血¹⁾(是/否)	83/87	2.349	1.020~5.408	0.045	55/30	2.530	0.552~11.601	0.232
内镜手术²⁾(是/否)	44/126	1.587	0.598~4.215	0.354	29/56	1.108	0.332~3.690	0.868
TIPS手术³⁾(是/否)	19/151	1.150	0.344~3.947	0.820	16/69	3.581	0.459~27.920	0.229
注：1)是否出血指纳入研究时是否出血；2)是否内镜手术指纳入研究至随访结束是否行内镜手术；3)是否TIPS指纳入研究至随访结束期间是否行TIPS手术。

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