能量代谢指标与失代偿期乙型肝炎肝硬化患者短期内自发性细菌性腹膜炎发生风险的相关性

陈秀敏; 林升龙; 王香梅; 马华晳; 张冬青; 廖资渊; 林明华; 高海兵

doi:10.3969/j.issn.1001-5256.2022.06.018

能量代谢指标与失代偿期乙型肝炎肝硬化患者短期内自发性细菌性腹膜炎发生风险的相关性

DOI: 10.3969/j.issn.1001-5256.2022.06.018

福建医科大学孟超肝胆医院重症肝病科，福州 350025

基金项目:

福建省医学创新课题 (2020CXB038);

福州市科技计划项目 (2021-S-240)

伦理学声明：研究方案于2018年7月6日通过福建医科大学孟超肝胆医院伦理委员会审核批准，批号：科审2018-027-01。

利益冲突声明：本研究不存在研究者、伦理委员会、受试者及公开研究成果有关的利益冲突。

作者贡献声明：陈秀敏、林升龙和高海兵负责提出研究选题，设计研究方案，实施研究过程，起草论文；林升龙和王香梅负责统计分析；马华晳、张冬青和廖资渊负责采集和整理数据；林明华负责指导性支持，设计论文框架，修订论文，终审论文。

详细信息

通信作者:
高海兵，gaohb605@163.com

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出版历程
- 收稿日期: 2021-11-15
- 录用日期: 2021-12-27
- 出版日期: 2022-06-20

Association of energy metabolic markers with the short-term risk of spontaneous bacterial peritonitis in patients with decompensated hepatitis B virus-related liver cirrhosis

Department of Severe Liver Diseases, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou 350025, China

Research funding:

Fujian Medical Innovation Program (2020CXB038);

Science and Technology Program of Fuzhou City (2021-S-240)

More Information

Corresponding author: GAO Haibing, gaohb605@163.com (ORCID:0000-0002-7266-1487)

摘要

摘要: 目的探讨失代偿期乙型肝炎肝硬化(HBV-LC)患者的间接能量代谢指标与自发性细菌性腹膜炎(SBP)发生风险的相关性。方法回顾性分析2017年11月—2019年11月福建医科大学孟超肝胆医院收治住院的失代偿期HBV-LC患者的临床资料，比较住院后2周内发生SBP和无SBP患者的基线临床参数和能量代谢指标的差异，采用logistic多因素回归分析患者发生SBP的相关风险因素。符合正态分布的计量资料两组间比较采用t检验；非正态分布的计量资料两组间比较采用Kruskal-Wallis H秩和检验。计数资料两组间比较采用χ²检验或Fisher精确检验。绘制受试者工作特征曲线(ROC曲线)分析新建立logistic回归模型的诊断效应，以最大Youden指数对应的点为模型的截断值，采用DeLong检验比较ROC曲线下面积(AUC)。结果纳入失代偿期HBV-LC患者50例，住院后2周内发生SBP患者23例(46%)，无SBP患者27例(54%)。SBP患者的甘油三酯、前白蛋白以及凝血酶原活动度(PTA)均显著低于无SBP患者(P值均＜0.05)；而SBP患者的国际标准化比值、C反应蛋白(CRP)和终末期肝病模型评分则显著高于无SBP患者(P值均＜0.05)。比较两组患者的基线能量代谢指标：SBP患者的呼吸熵(RQ)和碳水化合物氧化率(CHO)均较无SBP患者低[RQ: 0.79(0.76~0.86) vs 0.85(0.79~0.91), P=0.041; CHO: 20.50%(15.25%~41.05%) vs 41.6%(22.25%~68.05%), P=0.041]。logistic多因素回归分析提示PTA为失代偿期HBV-LC患者住院期间发生SBP的独立危险因素(比值比=0.004，P=0.008)，并以PTA、CRP、RQ和CHO等变量构建回归模型，模型AUC为85.0%，当曲线的Youden指数为最大值时，模型截断值为0.60，特异度为85.19%，敏感度为73.91%，模型的区分度优于CRP(AUC=74.5%, P=0.049)和PCT(AUC=56.4%, P＜0.01)。结论失代偿期HBV-LC患者短期内发生SBP的患者能量代谢指标RQ和CHO明显降低，结合PTA、CRP和CHO/RQ比值等指标，有助于临床医师早期判断SBP的高风险患者，并加强对高风险患者的营养支持。
- 乙型肝炎病毒 /
- 肝硬化 /
- 腹膜炎 /
- 能量代谢
Abstract: Objective To investigate the association of energy metabolic markers with the risk of spontaneous bacterial peritonitis (SBP) in patients with decompensated hepatitis B virus-related liver cirrhosis (HBV-LC). Methods A retrospective analysis was performed for the clinical data of the patients with decompensated HBV-LC who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2019, and baseline clinical parameters and energy metabolic markers were compared between the patients with SBP and those without SBP within 2 weeks after admission. A multivariate logistic regression analysis was performed to investigate the risk factors for SBP. The t-test was used for comparison of normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between two groups; the Fisher's exact test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency of the newly established logistic regression model, and with the corresponding point of Youden index as the cut-off value, the DeLong test was used to compare the area under the ROC curve (AUC). Results A total of 50 patients with decompensated HBV-LC were included, among whom 23 (46%) developed SBP within 2 weeks after admission and 27 (54%) had no SBP during hospitalization. Compared with the non-SBP patients, the SBP patients had significantly lower triglyceride, prealbumin, and prothrombin time activity (PTA) and significantly higher international normalization ratio, C-reactive protein (CRP), and Model for End-Stage Liver Disease score (all P < 0.05). Comparison of baseline energy metabolic markers showed that compared with the non-SBP patients, the SBP patients had significantly lower respiratory quotient (RQ) [0.79(0.76-0.86) vs 0.85(0.79-0.91), P=0.041] and carbohydrate oxidation (CHO) rate [20.50%(15.25%-41.05%) vs 41.6%(22.25%-68.05%), P=0.041]. The multivariate logistic regression analysis showed that PTA was an independent risk factor for SBP in the patients with decompensated HBV-LC during hospitalization (odd ratio=0.004, P=0.008), and the regression model established based on the variables including PTA, CRP, RQ, and CHO had an AUC of 85.0% and a cut-off value of 0.60 at the maximum Youden index, with a specificity of 85.19% and a sensitivity of 73.91%, suggesting that this model had a better discriminatory ability than CRP (AUC=74.5%, P=0.049) and procalcitonin (AUC=56.4%, P < 0.01). Conclusion There are significant reductions in the energy metabolic markers RQ and CHO in the patients with decompensated HBV-LC who develop SBP within a short term, and their combination with PTA, CRP, and CHO/RQ ratio can help clinicians identify the patients at a high risk of SBP in the early stage and enhance nutrition support for such patients.
- Hepatitis B virus /
- Liver Cirrhosis /
- Peritonitis /
- Energy Metabolism

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图 1 新模型、CRP和PCT的ROC曲线图

Figure 1. The ROC curves of the new model, CRP and PCT

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表 1 基线特征比较

Table 1. Comparison of baseline characteristics

指标	所有患者(n=50)	SBP组(n=23)	无SBP组(n=27)	统计值	P值
性别[例(%)]					0.689
女	7(14)	4(17)	3(11)
男	43(86)	19(83)	24(89)
肝衰竭[例(%)]				χ²=2.7	0.103
是	21(42)	13(57)	8(30)
否	29(58)	10(43)	19(70)
年龄(岁)	49.98±11.61	53.13±11.62	47.30±11.11	t=1.8	0.078
身高(cm)	168(165~170)	165(163~170)	168(165~170)	H=230.5	0.117
体质量(kg)	62.1(55.2~72.0)	63.0(53.7~71.0)	61.0(55.9~71.9)	H=304.5	0.915
体表面积(m²)	1.73±0.17	1.71±0.16	1.74±0.18	H=-0.7	0.517
BMI[例(%)]					0.793
下降	5(10)	2(9)	3(11)
正常	32(64)	14(61)	18(67)
超重	10(20)	6(26)	4(15)
肥胖	3(6)	1(4)	2(7)

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表 2 实验室指标比较

Table 2. Comparison of laboratory parameters

指标	所有患者(n=50)	SBP组(n=23)	无SBP组(n=27)	统计值	P值
总胆红素(μmol/L)	124.95(43.75~274.40)	185.80(83.40~280.60)	77.70(29.30~245.45)	H=403.0	0.073
白蛋白(g/L)	33.2±5.8	31.6±5.4	34.6±5.9	t=-1.8	0.071
前白蛋白(g/L)	55(45~88)	50(38~65)	78(51~126)	H=177.5	0.010
胆碱酯酶(U/L)	3401(2230~5029)	3120(2094~4299)	4111(2367~5396)	H=256.5	0.298
血糖(mmol/L)	5.27(4.74~7.18)	5.50(4.68~6.58)	5.22(4.84~7.28)	H=311.0	0.992
甘油三酯(mmol/L)	0.88(0.71~1.20)	0.81(0.69~0.94)	1.09(0.76~1.27)	H=208.5	0.048
总胆固醇(mmol/L)	2.94±1.19	2.69±1.15	3.15±1.20	t=-1.4	0.179
低密度脂蛋白(mmol/L)	1.57±0.70	1.52±0.73	1.62±0.68	t=-0.5	0.600
高密度脂蛋白(mmol/L)	0.56(0.21~0.90)	0.46(0.17~0.65)	0.74(0.29~1.04)	H=216.5	0.069
血肌酐(μmol/L)	73(63~87)	70(65~85)	73(61~88)	H=306.5	0.946
PTA(%)	0.56±0.22	0.45±0.16	0.66±0.21	t= -4.0	＜0.001
INR	1.55(1.20~2.04)	1.99(1.50~2.46)	1.25(1.12~1.67)	H= 482.0	＜0.001
血红蛋白(g/L)	124.12±21.03	118.78±17.31	128.67±23.10	t=-1.7	0.091
血小板(×10⁹/L)	81.0(53.5~110.3)	74.0(51.5~95.0)	92.0(57.5~124.5)	H=234.5	0.142
MELD评分	16.81±6.84	19.83±6.22	14.25±6.37	t=3.1	0.003
CRP(mg/L)	8.37(3.32~14.79)	13.42(6.82~21.44)	6.79(2.05~9.42)	H=462.5	0.003
PCT(ng/mL)	0.36(0.11~0.71)	0.55(0.08~0.76)	0.35(0.15~0.60)	H=350.5	0.442
注：PCT，降钙素原。

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表 3 能量代谢指标比较

Table 3. Comparison of energy metabolism indices

指标	所有患者(n=50)	SBP组(n=23)	无SBP组(n=27)	统计值	P值
REE(kcal)	1 513.30±323.65	1 493.78±266.95	1 529.93±369.44	t=-0.4	0.691
pREE((kcal)	1396(1312~1565)	1383(1259~1504)	1401(1327~1594)	H=266.0	0.392
RQ	0.82(0.78~0.89)	0.79(0.76~0.86)	0.85(0.79~0.91)	H=205.0	0.041
npRQ	0.82(0.78~0.90)	0.79(0.76~0.86)	0.85(0.79~0.91)	H=210.0	0.051
FAT(%)	49.70(28.15~65.33)	55.80(40.85~69.30)	43.80(15.35~61.40)	H=385.0	0.149
CHO(%)	31.55(18.15~52.83)	20.50(15.25~41.05)	41.60(22.25~68.05)	H=205.0	0.041
PRO(%)	15.2(8.0~22.1)	15.1(5.1~24.4)	15.5(8.4~19.3)	H=302.5	0.884
CHO/RQ	0.38(0.23~0.59)	0.26(0.20~0.48)	0.49(0.28~0.62)	H=202.5	0.036
注：pREE，预测静息能量消耗；FAT，脂肪氧化率。

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表 4 logistic回归模型参数

Table 4. The parameters of logistic regression model

参数	系数	比值比	95%置信区间	Z值	P值
截距	2.18		0.611~163.911	1.559	0.119
PTA	-5.43	0.004	0.000~0.179	-2.634	0.008
CHO/RQ	-0.93	0.396	0.011~13.843	-0.517	0.605
CRP	0.08	1.086	1.012~1.204	1.899	0.058

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