同种异体原位肝移植术后早期死亡的危险因素分析

doi:10.3877/cma.j.issn.1674-0793.2026.03.002

目的

探索同种异体原位肝移植术后30 d内死亡的潜在危险因素，为围手术期个体化干预策略制定及术后风险预测提供科学依据。

方法

回顾性纳入2016年1月至2020年12月在首都医科大学附属北京朝阳医院行同种异体原位肝移植的受者进行研究，将术后30 d内死亡定义为术后早期死亡，并依据其发生情况将纳入受者分为早期生存组和早期死亡组。收集患者一般资料、术前实验室指标、术中情况等临床数据；采用受试者工作特征曲线（ROC）确定各指标最佳截断值；通过最小绝对收缩和选择算子（LASSO）回归筛选相关因素，进一步经单因素及多因素Logistic回归分析明确独立危险因素，并采用限制性立方样条（RCS）分析其与早期死亡风险的剂量-反应关系。

结果

共纳入535例肝移植受者，术后早期死亡36例（6.7%）。多因素Logistic回归分析显示，术中红细胞输注量>1 650 ml（OR=3.313，95% CI：1.397~7.857）、术中尿量≤1 115 ml（OR=3.245，95% CI：1.409~7.473）、术前血小板计数≤24.5×10⁹/L（OR=3.437，95% CI：1.194~9.895）及术前血糖≤4.8 mmol/L（OR=2.955，95% CI：1.286~6.791）为术后早期死亡的独立危险因素（均P<0.05）。RCS分析表明，术中红细胞输注量和尿量与早期死亡风险呈线性相关，而术前血小板计数与死亡风险呈显著非线性相关。

结论

术前血小板计数过低、术前低血糖、术中大量输注红细胞及术中尿量偏低是同种异体原位肝移植术后早期死亡的独立危险因素。术前应采取多种手段提升血小板计数至24.5×10⁹/L以上，而围手术期血糖的最佳范围，需要进一步明确。

关键词: 肝移植, 早期死亡, 危险因素, 血小板计数, 术前血糖, 红细胞输注量, 术中尿量

Objective

To explore the potential risk factors for mortality within 30 days after orthotopic liver transplantation (OLT) and provide scientific basis for formulating individualized perioperative intervention strategies and predicting postoperative risks.

Methods

This retrospective study included recipients who underwent OLT at Beijing Chao-Yang Hospital, Capital Medical University. Death within 30 days after surgery was defined as early postoperative mortality, and patients were grouped accordingly. General patient information, preoperative laboratory indicators, and intraoperative data were collected. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff values for each indicator. Least absolute shrinkage and selection operator (LASSO) regression was applied to screen factors relevant to early postoperative mortality, followed by univariate and multivariate Logistic regression analysis to identify independent risk factors. Restricted cubic spline (RCS) analysis was employed to examine the dose-response relationships between these factors and the risk of early mortality.

Results

A total of 535 OLT recipients were included, among whom 36 (6.7%) experienced early postoperative mortality. Multivariate Logistic regression analysis revealed that intraoperative erythrocyte transfusion >1 650 ml (OR=3.313, 95% CI: 1.397-7.857), intraoperative urine volume≤1 115 ml (OR=3.245, 95% CI: 1.409-7.473), preoperative platelet count≤24.5×10⁹/L (OR=3.437, 95% CI: 1.194-9.895), and preoperative blood glucose≤4.8 mmol/L (OR=2.955, 95% CI: 1.286-6.791) were independent risk factors for early postoperative mortality after OLT. RCS analysis indicated that intraoperative erythrocyte transfusion volume and urine volume showed linear correlations with the risk of early postoperative mortality, while preoperative platelet count exhibited a nonlinear correlation with the risk of early postoperative mortality.

Conclusions

Low preoperative platelet count, preoperative hypoglycemia, high intraoperative erythrocyte transfusion volume, and low intraoperative urine volume are independent risk factors for early postoperative mortality. Preoperative measures should be taken to increase platelet counts above 24.5×10⁹/L, while the optimal range for perioperative blood glucose requires further clarification.

Key words: Liver transplantation, Early mortality, Risk factors, Platelet count, Preoperative blood glucose, Erythrocyte transfusion volume, Intraoperative urine output

表1 两组行同种异体原位肝移植术患者基线资料的比较

变量	早期生存组(499例)	早期死亡组(36例)	统计量	P值
一般情况
年龄(岁)^a	53.0 (46.0, 59.5)	51.5 (42.3, 59.5)	-0.97	0.331
性别^b			0.60	0.437
女	98 (19.6)	9 (25.0)
男	401 (80.4)	27 (75.0)
BMI (kg/m²)^a	24.1 (21.8, 26.3)	24.2 (21.5, 26.0)	-0.43	0.667
MELD评分 (分)^a	14.1 (9.0, 21.6)	22.6 (14.5, 32.1)	-3.64	<0.001^c
肝脏原发疾病^b
肝细胞癌	214 (42.9)	10 (27.8)	3.15	0.076
乙型肝炎肝硬化	112 (22.44)	9 (25.00)	0.13	0.723
酒精性肝硬化	48 (9.62)	8 (22.22)	4.43	0.035^c
自身免疫性肝硬化	27 (5.41)	3 (8.33)	0.13	0.718
急性肝衰竭	30 (6.01)	2 (5.56)	<0.001	1.000
合并症^b
高血压	93 (18.64)	8 (22.22)	0.28	0.596
糖尿病	108 (21.64)	7 (19.44)	0.10	0.756
门静脉高压症	268 (53.71)	22 (61.11)	0.74	0.389
脾功能亢进	196 (39.28)	9 (25.00)	2.90	0.089
腹腔积液	251 (50.30)	22 (61.11)	1.57	0.210
肺部感染	37 (7.41)	6 (16.67)	2.74	0.098
腹腔感染	12 (2.40)	5 (13.89)	10.90	<0.001^c
肝肾综合征	25 (5.01)	6 (16.67)	6.36	0.012^c
肝性脑病	67 (13.43)	12 (33.33)	10.57	0.001^c
上消化道出血	37 (7.41)	4 (11.11)	0.23	0.631
术前辅助检查^a
血红蛋白 (g/L)	105.4 (82.5, 129.5)	93.0 (75.0, 120.0)	-1.93	0.053
血小板计数 (×10⁹/L)	66.0 (43.5, 122.5)	56.5 (28.5, 90.0)	-2.00	0.046^c
AST (U/L)	47.00 (32.0, 88.0)	57.50 (44.8, 147.6)	-2.33	0.020^c
ALT (U/L)	30.0 (20.0, 53.0)	41.5 (20.8, 84.8)	-1.71	0.087
总胆红素 (μmol/L)	54.5 (22.7, 305.6)	251.8 (36.2, 504.4)	-3.08	0.002^c
白蛋白 (g/L)	33.6 (29.5, 37.2)	30.6 (25.9, 33.8)	-3.18	<0.001^c
血肌酐 (μmol/L)	65.4 (54.1, 80.0)	78.47 (55.8, 167.1)	-2.15	0.032^c
血糖 (mmol/L)	6.4 (5.1, 6.5)	6.4 (4.6, 6.4)	-1.57	0.116
血钾 (mmol/L)	3.9 (3.6, 4.2)	3.8 (3.5, 4.1)	-0.87	0.386
凝血酶原活动度 (%)	62.4 (45.7, 77.6)	58.5 (32.2, 70.3)	-2.23	0.026^c
部分凝血酶活化时间 (s)	36.5 (30.0, 48.4)	51.6 (35.5, 78.7)	-3.51	<0.001^c
纤维蛋白原 (g/L)	1. 6 (1.1, 2.2)	1.2 (0.8, 1.8)	-2.01	0.044^c
术中情况^a
手术时长 (min)	472.5 (407.5, 550.0)	485.0 (435.0, 560.0)	-1.64	0.100
功能性热缺血时间 (min)	3.0 (2.0, 3.0)	3.0 (3.0, 3.0)	-0.63	0.525
冷缺血时间 (h)	6.0 (4.0, 7.0)	6.0 (4.0, 8.0)	-0.06	0.952
无肝期时长 (min)	119.0 (101.3, 144.3)	130.0 (108.0, 155.0)	-1.42	0.155
红细胞输注量 (ml)	800.0 (0.0, 1 600.0)	1 600.0 (800.0, 2 100.0)	-3.63	<0.001^c
输血浆量 (ml)	800.0 (400.0, 800.0)	800.0 (800.0, 1 200.0)	-2.22	0.027^c
输液量 (ml)	5 100.0 (4 300.0, 6 300.0)	4 325.0 (3 525.0, 5 825.0)	-3.35	0.001^c
出血量 (ml)	800.0 (500.0, 1 200.0)	1 100.0 (800.0, 1 700.0)	-2.88	0.004^c
尿量 (ml)	1 668.8 (1 140.0, 2 200.0)	935.0 (462.5, 1 623.75)	-4.65	<0.001^c

表1 两组行同种异体原位肝移植术患者基线资料的比较

变量	早期生存组(499例)	早期死亡组(36例)	统计量	P值
一般情况
年龄(岁)^a	53.0 (46.0, 59.5)	51.5 (42.3, 59.5)	-0.97	0.331
性别^b			0.60	0.437
女	98 (19.6)	9 (25.0)
男	401 (80.4)	27 (75.0)
BMI (kg/m²)^a	24.1 (21.8, 26.3)	24.2 (21.5, 26.0)	-0.43	0.667
MELD评分 (分)^a	14.1 (9.0, 21.6)	22.6 (14.5, 32.1)	-3.64	<0.001^c
肝脏原发疾病^b
肝细胞癌	214 (42.9)	10 (27.8)	3.15	0.076
乙型肝炎肝硬化	112 (22.44)	9 (25.00)	0.13	0.723
酒精性肝硬化	48 (9.62)	8 (22.22)	4.43	0.035^c
自身免疫性肝硬化	27 (5.41)	3 (8.33)	0.13	0.718
急性肝衰竭	30 (6.01)	2 (5.56)	<0.001	1.000
合并症^b
高血压	93 (18.64)	8 (22.22)	0.28	0.596
糖尿病	108 (21.64)	7 (19.44)	0.10	0.756
门静脉高压症	268 (53.71)	22 (61.11)	0.74	0.389
脾功能亢进	196 (39.28)	9 (25.00)	2.90	0.089
腹腔积液	251 (50.30)	22 (61.11)	1.57	0.210
肺部感染	37 (7.41)	6 (16.67)	2.74	0.098
腹腔感染	12 (2.40)	5 (13.89)	10.90	<0.001^c
肝肾综合征	25 (5.01)	6 (16.67)	6.36	0.012^c
肝性脑病	67 (13.43)	12 (33.33)	10.57	0.001^c
上消化道出血	37 (7.41)	4 (11.11)	0.23	0.631
术前辅助检查^a
血红蛋白 (g/L)	105.4 (82.5, 129.5)	93.0 (75.0, 120.0)	-1.93	0.053
血小板计数 (×10⁹/L)	66.0 (43.5, 122.5)	56.5 (28.5, 90.0)	-2.00	0.046^c
AST (U/L)	47.00 (32.0, 88.0)	57.50 (44.8, 147.6)	-2.33	0.020^c
ALT (U/L)	30.0 (20.0, 53.0)	41.5 (20.8, 84.8)	-1.71	0.087
总胆红素 (μmol/L)	54.5 (22.7, 305.6)	251.8 (36.2, 504.4)	-3.08	0.002^c
白蛋白 (g/L)	33.6 (29.5, 37.2)	30.6 (25.9, 33.8)	-3.18	<0.001^c
血肌酐 (μmol/L)	65.4 (54.1, 80.0)	78.47 (55.8, 167.1)	-2.15	0.032^c
血糖 (mmol/L)	6.4 (5.1, 6.5)	6.4 (4.6, 6.4)	-1.57	0.116
血钾 (mmol/L)	3.9 (3.6, 4.2)	3.8 (3.5, 4.1)	-0.87	0.386
凝血酶原活动度 (%)	62.4 (45.7, 77.6)	58.5 (32.2, 70.3)	-2.23	0.026^c
部分凝血酶活化时间 (s)	36.5 (30.0, 48.4)	51.6 (35.5, 78.7)	-3.51	<0.001^c
纤维蛋白原 (g/L)	1. 6 (1.1, 2.2)	1.2 (0.8, 1.8)	-2.01	0.044^c
术中情况^a
手术时长 (min)	472.5 (407.5, 550.0)	485.0 (435.0, 560.0)	-1.64	0.100
功能性热缺血时间 (min)	3.0 (2.0, 3.0)	3.0 (3.0, 3.0)	-0.63	0.525
冷缺血时间 (h)	6.0 (4.0, 7.0)	6.0 (4.0, 8.0)	-0.06	0.952
无肝期时长 (min)	119.0 (101.3, 144.3)	130.0 (108.0, 155.0)	-1.42	0.155
红细胞输注量 (ml)	800.0 (0.0, 1 600.0)	1 600.0 (800.0, 2 100.0)	-3.63	<0.001^c
输血浆量 (ml)	800.0 (400.0, 800.0)	800.0 (800.0, 1 200.0)	-2.22	0.027^c
输液量 (ml)	5 100.0 (4 300.0, 6 300.0)	4 325.0 (3 525.0, 5 825.0)	-3.35	0.001^c
出血量 (ml)	800.0 (500.0, 1 200.0)	1 100.0 (800.0, 1 700.0)	-2.88	0.004^c
尿量 (ml)	1 668.8 (1 140.0, 2 200.0)	935.0 (462.5, 1 623.75)	-4.65	<0.001^c

图1 最小绝对收缩和选择算法（LASSO）筛选肝移植术后早期死亡相关因素　A. 系数路径图；B. 交叉验证曲线

表2 肝移植术后早期死亡危险因素的单因素及多因素分析结果

变量	单因素分析			多因素分析
变量	OR	95% CI	P值	OR	95% CI	P值
MELD评分>20.8分	4.369	2.172~8.789	<0.001^a	1.923	0.847~4.364	0.118
合并酒精性肝硬化	2.685	1.159~6.220	0.021^a	2.403	0.912~6.327	0.076
合并腹腔感染	6.546	2.169~19.756	0.001^a	2.100	0.574~7.689	0.262
手术时长>432.5 min	2.446	1.229~4.867	0.011^a	1.509	0.632~3.606	0.354
无肝期时长>104.5 min	2.388	1.181~4.827	0.015^a	1.899	0.824~4.377	0.132
术中红细胞输注量>1 650 ml	4.668	2.312~9.427	<0.001^a	3.313	1.397~7.857	0.007^a
术中输液量≤4 375 ml	3.076	1.552~6.094	0.001^a	1.740	0.777~3.893	0.178
术中尿量≤1 115 ml	6.114	2.969~12.589	<0.001^a	3.245	1.409~7.473	0.006^a
术前血小板计数≤24.5×10⁹/L	6.899	2.911~16.346	<0.001^a	3.437	1.194~9.895	0.022^a
术前血糖≤4.8 mmol/L	2.640	1.288~5.412	0.008^a	2.955	1.286~6.791	0.011^a

表2 肝移植术后早期死亡危险因素的单因素及多因素分析结果

变量	单因素分析			多因素分析
变量	OR	95% CI	P值	OR	95% CI	P值
MELD评分>20.8分	4.369	2.172~8.789	<0.001^a	1.923	0.847~4.364	0.118
合并酒精性肝硬化	2.685	1.159~6.220	0.021^a	2.403	0.912~6.327	0.076
合并腹腔感染	6.546	2.169~19.756	0.001^a	2.100	0.574~7.689	0.262
手术时长>432.5 min	2.446	1.229~4.867	0.011^a	1.509	0.632~3.606	0.354
无肝期时长>104.5 min	2.388	1.181~4.827	0.015^a	1.899	0.824~4.377	0.132
术中红细胞输注量>1 650 ml	4.668	2.312~9.427	<0.001^a	3.313	1.397~7.857	0.007^a
术中输液量≤4 375 ml	3.076	1.552~6.094	0.001^a	1.740	0.777~3.893	0.178
术中尿量≤1 115 ml	6.114	2.969~12.589	<0.001^a	3.245	1.409~7.473	0.006^a
术前血小板计数≤24.5×10⁹/L	6.899	2.911~16.346	<0.001^a	3.437	1.194~9.895	0.022^a
术前血糖≤4.8 mmol/L	2.640	1.288~5.412	0.008^a	2.955	1.286~6.791	0.011^a

图2 独立危险因素与肝移植术后早期死亡的限制性立方样条（RCS）曲线　A. 术中输血；B. 术中尿量；C. 术前血小板计数；D. 术前血糖

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Analysis of risk factors for early mortality after orthotopic liver transplantation

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Analysis of risk factors for early mortality after orthotopic liver transplantation