小剂量血浆置换联合双重血浆分子吸附系统/血液灌流治疗慢加急性肝衰竭的效果分析

鲁杰; 李顶春; 刘叶; 袁琳娜; 段志文; 李武

doi:10.3969/j.issn.1001-5256.2022.11.017

小剂量血浆置换联合双重血浆分子吸附系统/血液灌流治疗慢加急性肝衰竭的效果分析

DOI: 10.3969/j.issn.1001-5256.2022.11.017

昆明医科大学第一附属医院感染与肝病科，昆明 650032

基金项目:

国家自然科学基金 (82160801);

云南省“万人计划”名医专项 (Yunrenweifa (2020)20, RLMY20200015);

云南省科技厅-应用基础研究联合专项资金项目 (2018FE001 (-214))

伦理学声明：本研究方案于2021年2月26日由昆明医科大学伦理委员会审批，批号：2021-206。

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：鲁杰负责课题设计，资料分析，撰写论文；李顶春、刘叶、袁琳娜参与收集数据；段志文负责修改论文；李武指导撰写论文并最后定稿。

详细信息

通信作者:
李武，liwukm@qq.com

计量
- 文章访问数: 332
- HTML全文浏览量: 114
- PDF下载量: 53
- 被引次数: 0
出版历程
- 收稿日期: 2022-04-25
- 录用日期: 2022-06-20
- 出版日期: 2022-11-20

Clinical efficacy of low-dose plasma exchange combined with double plasma molecular absorption system/hemoperfusion in treatment of acute-on-chronic liver failure

Department of Infection and Liver Diseases, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China

Research funding:

National Natural Science Foundation of China (82160801);

Yunnan Province Famous Doctor Project (Yunrenweifa (2020)20, RLMY20200015);

Yunnan Provincial Department of Science and Technology -Applied Basic Research Joint Special Fund Project (2018FE001 (-214))

More Information

Corresponding author: LI Wu, liwukm@qq.com(ORCID: 0000-0002-1222-3629)

摘要

摘要: 目的研究小剂量血浆置换(PE)的组合人工肝治疗慢加急性肝衰竭(ACLF)的临床疗效以及对分层后病死率的影响。方法纳入2018年1月—2020年12月于昆明医科大学第一附属医院感染与肝病科收治的ACLF患者共272例，分为小剂量PE联合双重血浆分子吸附系统(DPMAS)/血液灌流(HP)组(n=190)和单纯内科治疗组(n=82)。收集两组患者治疗前、后的实验室指标，比较临床疗效；将两组患者按《肝衰竭诊治指南(2018年版)》分层(前期、早中期、晚期或A、B、C型)，随访所有患者出院后12周(短期)、48周(长期)的一般情况及死亡。正态分布的计量资料两组间比较采用独立样本t检验，治疗前后比较采用配对样本t检验；不符合正态分布计量资料两组间比较用Mann-Whitney U检验，治疗前后比较采用Wilcoxon检验。计数资料组间比较采用χ²检验。结果小剂量PE联合DPMAS/HP与单纯内科治疗均能降低ACLF患者的ALT、AST、TBil、血氨水平，升高Alb水平，两组治疗前后差异均有统计学意义(P值均＜0.05)，但是小剂量PE联合DPMAS/HP治疗比单纯内科治疗组能更好地清除ALT、TBil和血氨，改善Alb，各指标治疗前后差值比较均有统计学意义(P值均＜0.05)。小剂量PE联合DPMAS/HP治疗后能显著降低胆汁酸、INR、中性粒细胞/淋巴细胞比值、MELD评分，升高血小板与白细胞比率，治疗前后差异均有统计学意义(P值均＜0.05)，而单纯内科治疗不能改善以上指标，治疗前后差异无统计学意义(P值均＞0.05)。与单纯内科治疗组相比，小剂量PE联合DPMAS/HP治疗能降低ACLF患者短期病死率，尤其是能显著降低前期、早中期、A型患者短期病死率，两组间差异均有统计学意义(P值均＜0.05)。在小剂量PE联合DPMAS/HP治疗组中，前期患者短期/长期病死率均显著低于晚期，A型患者短期/长期病死率均显著低于C型，差异均有统计学意义(P值均＜0.05)。结论小剂量PE联合DPMAS/HP治疗具有较好的临床疗效，能有效降低ACLF的短期病死率，尤其能显著降低前期、早中期和A型患者的短期病死率。
- 慢加急性肝功能衰竭 /
- 血浆置换 /
- 肝, 人工 /
- 治疗结果
Abstract: Objective To investigate the clinical efficacy of low-dose plasma exchange (PE) combined with artificial liver in the treatment of acute-on-chronic liver failure (ACLF) and its effect on mortality rate after stratification. Methods A total of 272 ACLF patients who were admitted to Department of Infection and Hepatology, The First Affiliated Hospital of Kunming Medical University, from January 2018 to December 2020 were enrolled and divided into low-dose PE+double plasma molecular absorption system (DPMAS)/hemoperfusion (HP) group (n=190) and medical treatment group(n=82). Laboratory markers were collected before and after treatment, and clinical outcome was compared between the two groups; stratified analysis (early stage, early-middle stage, late stage or types A, B, C) was performed for the two groups according to Diagnostic and treatment guidelines for liver failure (2018 edition), and all patients were followed up to observe general status and death at 12 weeks (short-term) and 48 weeks (long-term) after discharge. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the paired samples t-test was used for comparison before and after treatment; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Wilcoxon test was used for comparison before and after treatment; the chi-square test was used for comparison of categorical data between groups. Results Both low-dose PE combined with DPMAS/HP and medical treatment alone could reduce the levels of alanine aminotransferase (ALT), aspartate aminotransferase, total bilirubin (TBil), and blood ammonia and increase the level of albumin (Alb), and both groups had significant changes in these indices after treatment (all P < 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP better reduced ALT, TBil, and blood ammonia and improved Alb, with significant changes in these indices after treatment (all P < 0.05). Low-dose PE combined with DPMAS/HP could significantly reduce bile acid, international normalized ratio, neutrophil-lymphocyte ratio, and MELD score and increase platelet-to-white blood cell ratio (all P < 0.05), while medical treatment alone could not improve the above indices (all P > 0.05). Compared with medical treatment alone, low-dose PE combined with DPMAS/HP could reduce the short-term mortality rate of ACLF patients, especially the short-term mortality rate of ACLF patients with early-stage, early-middle-stage or type A ACLF, and there were significant differences between the two groups (all P < 0.05). In the low-dose PE+DPMAS/HP group, the patients with early-stage ACLF had significantly lower short- and long-term mortality rates than those with late-stage ACLF, and the patients with type A ACLF had significantly lower short- and long-term mortality rates than those with type C ACLF (all P < 0.05). Conclusion Low-dose PE combined with DPMAS/HP has good clinical efficacy and can effectively reduce the short-term mortality rate of ACLF, especially the short-term mortality rate of patients with early-stage, early-middle-stage, or type A ACLF.
- Acute-On-Chronic Liver Failure /
- Plasma Exchange /
- Liver, Artificial /
- Treatment Outcome

HTML全文

表 1 两组患者一般资料比较

Table 1. Comparison of general data of the two groups of patients

指标	小剂量PE+DPMAS/HP组(n=190)	单纯内科治疗组(n=82)	统计值	P值
分期(前期/早中期/晚期，例)	73/89/28	36/34/12	χ²=-0.676	0.499
分型(A型/B型/C型，例)	67/34/89	14/12/56	χ²=-3.409	0.001
女/男(例)	37/153	17/65	χ²=0.057	0.811
年龄(岁)	46.8±11.5	52.0±11.5	t=-3.396	0.001
ACLF病因[例(%)]
HBV	114(60.0)	26(31.7)	χ²=18.356	＜0.001
HCV	4(2.1)	4(4.9)	χ²=0.724	0.395
药物	15(7.9)	19(23.2)	χ²=12.221	＜0.001
酒精性肝病	48(25.3)	19(23.2)	χ²=0.135	0.713
自身免疫性肝病	15(7.9)	8(9.8)	χ²=0.256	0.613
其他肝病	8(4.2)	8(9.8)	χ²=2.259	0.133

下载: 导出CSV

表 2 两组患者治疗前后临床疗效对比

Table 2. Comparison of clinical efficacy between the two groups

指标	组别	治疗前	治疗后	统计值	P值
Alb(g/L)	小剂量PE+DPMAS/HP组	31.3(28.0~35.4)	36.0(34.0~37.3)	Z=-7.125	＜0.001
	单纯内科治疗组	29.3±6.5	31.7±4.9	t=3.354	0.001
AST(U/L)	小剂量PE+DPMAS/HP组	178.6(84.7~441.8)	86.1(58.9~159.2)	Z=-9.425	＜0.001
	单纯内科治疗组	136.5(59.8~298.3)	60.3(34.4~101.5)	Z=-6.752	＜0.001
ALT(U/L)	小剂量PE+DPMAS/HP组	149.4(52.3~484.7)	58.0(39.8~114.0)	Z=-10.097	＜0.001
	单纯内科治疗组	50.5(34.3~203.3)	43.8(24.0~71.0)	Z=-4.639	＜0.001
TBil(mg/dL)	小剂量PE+DPMAS/HP组	19.6(12.8~25.2)	8.2(4.9~13.7)	Z=-10.184	＜0.001
	单纯内科治疗组	12.0(6.7~22.4)	6.7(3.5~12.1)	Z=-3.497	＜0.001
血氨(μmol/L)	小剂量PE+DPMAS/HP组	88.0(77.7~105.3)	45.5(26.1~63.0)	Z=-11.825	＜0.001
	单纯内科治疗组	92.8(74.5~127.5)	68.5(55.0~89.4)	Z=-7.427	＜0.001
胆汁酸(μmol/L)	小剂量PE+DPMAS/HP组	223.7(163.4~282.9)	160.0(109.2~221.7)	Z=-6.069	＜0.001
	单纯内科治疗组	134.7(71.2~222.0)	138.0(79.7~218.0)	Z=-0.981	0.327
INR	小剂量PE+DPMAS/HP组	1.7(1.3~2.3)	1.7(1.4~2.0)	Z=-3.500	0.002
	单纯内科治疗组	1.5(1.3~2.2)	1.6(1.4~1.9)	Z=-0.890	0.373
NLR	小剂量PE+DPMAS/HP组	3.8(2.4~5.8)	5.1(2.8~8.8)	Z=-3.050	0.002
	单纯内科治疗组	3.6(2.3~6.3)	3.4(1.9~7.8)	Z=-0.243	0.808
PWR	小剂量PE+DPMAS/HP组	14.5(9.8~22.6)	16.2(11.6~24.9)	Z=-2.551	0.011
	单纯内科治疗组	16.2(8.3~25.0)	18.4(13.7~23.0)	Z=-0.784	0.433
MELD	小剂量PE+DPMAS/HP组	19.0(14.6~24.4)	17.2(11.9~22.9)	Z=-4.796	＜0.001
	单纯内科治疗组	16.5(11.2~21.6)	15.4(10.5~20.2)	Z=-0.793	0.428

下载: 导出CSV

表 3 两组治疗前后差值的比较

Table 3. Comparison of the Δvalue between the two groups

指标	小剂量PE+DPMAS/HP组	单纯内科治疗组	Z值	P值
ΔAlb(g/L)	-3.7(-7.5~0.7)	-1.8(-5.5~2.3)	-2.797	0.005
ΔALT(U/L)	74.5(6.8~336.5)	22.2(0.3~172.0)	-2.695	0.007
ΔAST(U/L)	60.7(13.3~278.0)	67.8(-18.3~187.2)	-0.180	0.857
ΔTBil(mg/dL)	10.0(4.6~15.5)	2.9(-0.8~11.8)	-4.070	＜0.001
Δ血氨(μmol/L)	38.1(26.1~63.0)	23.1(11.0~43.0)	-1.828	0.034

下载: 导出CSV

表 4 两组患者分期后病死率比较

Table 4. Comparison of mortality after staging between the two groups of patients

指标	小剂量PE+DPMAS/HP组(n=190)	单纯内科治疗组(n=82)	χ²值	P值
短期病死率[例(%)]
前期	16(12.3)	15(41.7)	4.620	0.032
早中期	29(32.6)	21(61.8)	8.683	0.003
晚期	15(53.6)	8(66.7)	0.598	0.443
长期病死率[例(%)]
前期	38(52.1)	24(66.7)	2.099	0.147
早中期	69(77.5)	28(82.4)	0.344	0.558
晚期	22(78.6)	10(83.3)	0.119	0.730

下载: 导出CSV

表 5 两组患者分型后病死率比较

Table 5. Comparison of mortality after classification between the two groups of patients

指标	小剂量PE+DPMAS/HP组(n=190)	单纯内科治疗组(n=82)	χ²值	P值
短期病死率[例(%)]
A型	10(14.9)	6(42.9)	5.700	0.017
B型	10(29.4)	6(50.0)	1.657	0.198
C型	40(44.9)	32(57.1)	2.046	0.153
长期病死率[例(%)]
A型	33(49.3)	8(57.1)	0.288	0.591
B型	25(73.5)	9(75.0)	0.010	0.921
C型	71(79.8)	45(80.4)	0.007	0.932

下载: 导出CSV

参考文献(20)

[1]	HERNAEZ R, SOLÀ E, MOREAU R, et al. Acute-on-chronic liver failure: an update[J]. Gut, 2017, 66(3): 541-553. DOI: 10.1136/gutjnl-2016-312670.
[2]	ZHANG XL. Clinical study of combined non-biological artificial liver technology in the treatment of liver failure under the condition of blood stress[D]. Kunming: Kunming Medical University, 2018. 张秀灵. 血源紧张条件下组合型非生物人工肝技术治疗肝衰竭的临床研究[D]. 昆明: 昆明医科大学, 2018.
[3]	ZHANG XL, DUAN ZW, YANG RD, et al. Clinical study of plasma exchange combined with dual plasma molecular adsorption system in the treatment of patients with early and mid-stage liver failure under the condition of blood stress[J]. J Prac Hepatol, 2019, 22(2): 289-290. DOI: 10.3969/j.issn.1672-5069.2019.02.034. 张秀灵, 段志文, 杨瑞东, 等. 血源紧张条件下血浆置换联合双重血浆分子吸附系统治疗早中期肝衰竭患者临床研究[J]. 实用肝脏病杂志, 2019, 22(2): 289-290. DOI: 10.3969/j.issn.1672-5069.2019.02.034.
[4]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007. 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35(1): 38-44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.
[5]	Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Expert consensus on clinical application of artificial liver and blood purification (2022 edition)[J]. J Clin Hepatol, 2022, 38(4): 767-775. DOI: 10.3969/j.issn.1001-5256.2022.04.007. 中华医学会肝病学分会重型肝病与人工肝学组. 人工肝血液净化技术临床应用专家共识(2022年版)[J]. 临床肝胆病杂志, 2022, 38(4): 767-775 DOI: 10.3969/j.issn.1001-5256.2022.04.007.
[6]	FAN Q, LI Z, Liver transplantation for chronic acute liver failure[J]. Qgran Transplant, 2022, 13(3): 333-337. DOI: 10.3969/j.issn.1674-7445.2022.03.008. 范祺, 李照. 慢加急性肝衰竭的肝移植治疗[J]. 器官移植, 2022, 13(3): 333-337. DOI: 10.3969/j.issn.1674-7445.2022.03.008.
[7]	SUN KY, MAO JX, LIU Y, et al. Influencing factors of curative effect of plasma exchange in patients with HBV-related acute-on-chronic liver failure waiting for liver transplantation[J/CD]. Chin J Hepat Surg(Electronic Edition), 2022, 11(3): 252-257. DOI: 10.3877/cma.j.issn.2095-3232.2022.03.008. 孙克彦, 毛家玺, 刘业, 等. HBV相关性慢加急性肝衰竭等待肝移植患者血浆置换疗效影响因素[J/CD]. 中华肝脏外科手术学电子杂志, 2022, 11(3): 252-257. DOI: 10.3877/cma.j.issn.2095-3232.2022.03.008.
[8]	LARSEN FS, SCHMIDT LE, BERNSMEIER C, et al. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial[J]. J Hepatol, 2016, 64(1): 69-78. DOI: 10.1016/j.jhep.2015.08.018.
[9]	YUAN S, QIAN Y, TAN D, et al. Therapeutic plasma exchange: A prospective randomized trial to evaluate 2 strategies in patients with liver failure[J]. Transfus Apher Sci, 2018, 57(2): 253-258. DOI: 10.1016/j.transci.2018.02.001.
[10]	BJURSTEN LM, RASMUSSON L, OH S, et al. Titanium dioxide nanotubes enhance bone bonding in vivo[J]. J Biomed Mater Res A, 2010, 92(3): 1218-1224. DOI: 10.1002/jbm.a.32463.
[11]	YAO J, LI S, ZHOU L, et al. Therapeutic effect of double plasma molecular adsorption system and sequential half-dose plasma exchange in patients with HBV-related acute-on- chronic liver failure[J]. J Clin Apher, 2019, 34(4): 392-398. DOI: 10.1002/jca.21690.
[12]	SUN J, GUO H, YU X, et al. A neutrophil-to-lymphocyte ratio-based prognostic model to predict mortality in patients with HBV-related acute-on-chronic liver failure[J]. BMC Gastroenterol, 2021, 21(1): 422. DOI: 10.1186/s12876-021-02007-w.
[13]	CHIRIAC S, STANCIU C, SINGEAP AM, et al. Prognostic value of neutrophil-to-lymphocyte ratio in cirrhotic patients with acute-on-chronic liver failure[J]. Turk J Gastroenterol, 2020, 31(12): 868-876. DOI: 10.5152/tjg.2020.19838.
[14]	JIE Y, GONG J, XIAO C, et al. Low platelet to white blood cell ratio indicates poor prognosis for acute-on-chronic liver failure[J]. Biomed Res Int, 2018, 2018: 7394904. DOI: 10.1155/2018/7394904.
[15]	YANG L, WU T, LI J, et al. Artificial liver treatment improves survival in patients with hepatitis B virus-related acute-on-chronic liver failure: A case-control matched analysis[J]. Hepatol Res, 2020, 50(6): 656-670. DOI: 10.1111/hepr.13497.
[16]	LIU H, ZHANG Q, LIU L, et al. Effect of artificial liver support system on short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure[J]. Artif Organs, 2020, 44(10): E434-E447. DOI: 10.1111/aor.13710.
[17]	GUO X, WU F, GUO W, et al. Comparison of plasma exchange, double plasma molecular adsorption system, and their combination in treating acute-on-chronic liver failure[J]. J Int Med Res, 2020, 48(6): 300060520932053. DOI: 10.1177/0300060520932053.
[18]	CHEN JJ, HUANG JR, YANG Q, et al. Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-on-chronic liver failure: a nationwide prospective multicenter study in China[J]. Hepatobiliary Pancreat Dis Int, 2016, 15(3): 275-281. DOI: 10.1016/s1499-3872(16)60084-x.
[19]	CHEN YY, LI H, XU BY, et al. Plasma exchange-based non-bioartificial liver support system improves the short-term outcomes of patients with hepatitis B virus-associated acute-on-chronic liver failure: A multicenter prospective cohort study[J]. Front Med (Lausanne), 2021, 8: 779744. DOI: 10.3389/fmed.2021.779744.
[20]	TAN ZQ. Analysis of risk factors for the prognosis of patients with hepatitis B-related acute-on-chronic liver failure[D]. Nanchang: Nanchang University, 2021. 谭志强. 乙型肝炎相关慢加急性肝衰竭患者预后的危险因素分析[D]. 南昌: 南昌大学, 2021.