血清总胆红素水平在炎症性肠病中临床意义的meta分析

doi:10.3969/j.issn.1004-583X.2023.08.001

摘要/Abstract

摘要：

目的探讨血清总胆红素(serum total bilirubin, STB)在炎症性肠病(Inflammatory Bowel Disease,IBD)患者中的临床意义。方法计算机检索PubMed、Embase、Web of Science、Cochrane Library、中国知网、维普、万方、中国生物医学文献(CBM)等数据库从建库至2022年11月有关STB与IBD相关性的病例对照研究, 使用NOS评分对纳入文献进行评价,采用RevMan5.4.1和Stata13.1软件进行统计学分析。结果共纳入14篇文献18项研究,包括6067例参与者(IBD组2972例和对照组3905例)。Meta分析结果显示:①IBD患者STB水平低于对照组(SMD=-0.80, 95%CI: -0.99~-0.61, P<0.01);②活动期IBD患者STB水平较缓解期更低(SMD=-0.76, 95%CI: -1.33~-0.19, P=0.009);③随着IBD严重程度的增加,STB呈下降趋势(轻度比中度:SMD=-0.35,95%CI: -0.52~-0.18, P<0.01;中度比重度:SMD=-0.59,95%CI: -0.78~-0.39, P<0.01;轻度比重度:SMD=-0.88,95%CI: -1.10~-0.66,P<0.01); ④STB水平与血沉(Erythrocyte Sedimentation Rate,ESR)、C反应蛋白(C-reactive protein,CRP)及IBD疾病活动度评分呈负相关,与血红蛋白(Hemoglobin,Hb)呈正相关(ESR:r=-0.41, 95%CI:-0.45~-0.35,P<0.01; CRP: r=-0.37, 95%CI: -0.48~-0.26, P<0.01;临床评分: r=-0.54, 95%CI:-0.70~-0.39, P<0.01; Hb: r=0.45, 95%CI: 0.40~0.50, P<0.01);⑤正常范围内低水平的STB发生IBD的风险为高水平的3.15倍(OR=3.15,95%CI:2.24~4.44,P<0.01)。结论正常范围内低水平的STB可能与IBD的发生风险增加有关,且其水平与IBD疾病活动性及严重程度相关,对于IBD的临床评估可能有参考价值。

关键词: 胆红素, 炎性肠疾病, 荟萃分析, 病例对照研究

Abstract:

Objective To systematically evaluate the clinical significance of serum total bilirubin (STB) in patients with inflammatory bowel disease (IBD). Methods Case-control studies on the correlation between STB and IBD published from their inception to November 2022 were searched in online databases, including the PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wanfang, and Chinese Biomedical Databases (CBM). The quality of recruited articles was assessed using the Newcastle-Ottawa Scale (NOS). RevMan 5.4.1 and Stata13.1 were used for data analysis. Results A total of 14 articles, involving 6067 participants in 18 case-control studies (2972 in IBD group and 3905 in control group) were enrolled in this meta-analysis. STB was significantly lower in IBD patients than that of controls (SMD=-0.80, 95%CI:-0.99, -0.61, P<0.01). STB level in the active stage of IBD was significantly lower than that in remission stage (SMD=-0.76, 95%CI:-1.33, -0.19, P=0.009). STB decreased with the increase of IBD severity (mild vs moderate: SMD=-0.35, 95%CI:-0.52,-0.18, P<0.01; moderate vs severe: SMD=-0.59, 95%CI:-0.78, -0.39, P<0.01; mild vs severe: SMD=-0.88, 95%CI:-1.10, -0.66, P<0.01). STB level was negatively correlated with erythrocyte sedimentation rate (ESR) (r=-0.41, 95%CI:-0.45, -0.35, P<0.01), C-reactive protein (CRP) (r=-0.37, 95%CI:-0.48, -0.26, P<0.01) and clinical score (r=-0.54, 95%CI:-0.70, -0.39; P<0.01), and positively correlated with hemoglobin (Hb)(r=0.45, 95%CI:0.40, 0.50; P<0.01). The risk of IBD in patients with low-level STB within the normal range was 3.15 times higher than that of patients with high-level STB (OR=3.15, 95%CI:2.24, 4.44, P<0.01). Conclusion Low-level STB within the normal range is correlated with the increased risk, disease activity and severity of IBD, which may have reference values for clinical evaluation of IBD.

Key words: bilirubin, inflammatory bowel disease, meta analysis, case-control study

中图分类号:

R574

陈晓天, 霍丽娟. 血清总胆红素水平在炎症性肠病中临床意义的meta分析[J]. 临床荟萃, 2023, 38(8): 677-685.

Chen Xiaotian, Huo Lijuan. Meta-analysis of clinical significance of serum total bilirubin level in inflammatory bowel disease[J]. Clinical Focus, 2023, 38(8): 677-685.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2023.08.001

https://huicui.hebmu.edu.cn/CN/Y2023/V38/I8/677

图/表 14

图1 文献筛选流程图

Fig. 1 Flow chart of document screening

表1 纳入文献的基本特征

Tab.1 Basic characteristics of the eligible literature

作者	年份	国家	病例组	对照组	样本量(男/女)		结局指标	STB水平分组	低水平STB发生 IBD的OR值	NOS 评分
作者	年份	国家	病例组	对照组	病例组	对照组	结局指标	STB水平分组	低水平STB发生 IBD的OR值	NOS 评分
$L e n í ˇ c e k [5]$	2014	捷克	CD	健康人	31/59	126/103	①	-	-	7
Schieffer^[6](UC1)	2017	美国	UC	健康人	187	187	①⑧	≤0.5 mg/dl 0.51~0.60 mg/dl 0.61~0.80 mg/dl ≥0.81	1.98(1.09-3.63) 0.84(0.42-1.69) 0.78(0.40-1.55) 参照	7
Schieffer^[6](CD1)	2017	美国	CD	健康人	254	254	①⑧	≤0.5 mg/dl 0.51~0.60 mg/dl 0.61~0.80 mg/dl ≥0.81	1.91(1.26-2.91) 1.00(0.62-1.63) 1.11(0.69-1.79) 参照	7
Schieffer^[6](UC2)	2017	美国	UC	健康人	124	124	①⑧	≤0.4 mg/dl 0.41~0.50 mg/dl 0.51~0.67 mg/dl ≥0.68	6.07(3.01-12.75) 4.68(2.17-10.45) 2.73(1.22-6.21) 参照	7
Schieffer ^[6](CD2)	2017	美国	CD	健康人	233	233	①⑧	≤0.4 mg/dl 0.41~0.50 mg/dl 0.51~0.67 mg/dl ≥0.68	3.60(2.19-5.99) 1.55(0.85-2.81) 1.35(0.76-2.41) 参照	7
Tian ^[11]	2018	中国武汉	UC	健康人	170	200	①⑧	<8.14 μmol/L 8.14~11.01 mg/dl 11.02~14.77 mg/dl >14.77	2.56(1.54-4.25) 2.42(1.44-4.07) 1.52(0.97-2.51) 参照	7
陈影影^[12]	2018	中国徐州	UC	肠镜无异常者	27/28	38/37	①③	-	-	6
蒋传林^[13]	2018	中国武汉	CD	健康人	50/30	92/68	①⑧	<7.63 μmol/L 7.63~11.00 μmol/L 11.01~14.72 μmol/L >14.72	4.86(1.87-10.75) 3.14(1.38-8.44) 2.82(0.56-3.78) 参照	7
Su^[14]	2019	中国广西	CD	健康人	47/24	82/43	①②③	-	-	9
Shi ^[15]	2019	中国西安	UC	健康人	47/53	68/72	①②③④⑤⑧	<8.3 μmol/L 8.3~11.1 μmol/L 11.1~14.472 μmol/L ≥14.472	5.14(2.32-11.39) 2.69(1.23-5.90) 1.99(0.90-4.39) 参照	7
Zhao ^[16](UC)	2019	中国南京	UC	健康人	124/87	134/121	①④⑤⑥⑦	-	-	8
Zhao ^[16](CD)	2019	中国南京	CD	健康人	169/73	134/121	①④⑤⑥⑦	-	-	8
王春莹^[17]	2020	中国西安	UC	健康人	58/32	56/34	①②③⑥	-	-	6
谭丽^[18]	2020	中国吉林	UC	健康人	189/172	43/68	①③	-	-	7
Zhang^[19]	2020	中国南京	UC	健康人	264/184	190/118	①④⑤⑦	-	-	7
Zhou^[7]	2022	中国四川	CD	健康人	66/76	125/114	①⑥	-	-	7
刘奇^[20]	2022	中国河南	UC	肠镜无异常者	28/30	32/33	①③	-	-	6
黄冠华^[21]	2022	中国河南	UC	健康人	31/23	28/22	①②③⑥	-	-	6

表1 纳入文献的基本特征

Tab.1 Basic characteristics of the eligible literature

作者	年份	国家	病例组	对照组	样本量(男/女)		结局指标	STB水平分组	低水平STB发生 IBD的OR值	NOS 评分
作者	年份	国家	病例组	对照组	病例组	对照组	结局指标	STB水平分组	低水平STB发生 IBD的OR值	NOS 评分
$L e n í ˇ c e k [5]$	2014	捷克	CD	健康人	31/59	126/103	①	-	-	7
Schieffer^[6](UC1)	2017	美国	UC	健康人	187	187	①⑧	≤0.5 mg/dl 0.51~0.60 mg/dl 0.61~0.80 mg/dl ≥0.81	1.98(1.09-3.63) 0.84(0.42-1.69) 0.78(0.40-1.55) 参照	7
Schieffer^[6](CD1)	2017	美国	CD	健康人	254	254	①⑧	≤0.5 mg/dl 0.51~0.60 mg/dl 0.61~0.80 mg/dl ≥0.81	1.91(1.26-2.91) 1.00(0.62-1.63) 1.11(0.69-1.79) 参照	7
Schieffer^[6](UC2)	2017	美国	UC	健康人	124	124	①⑧	≤0.4 mg/dl 0.41~0.50 mg/dl 0.51~0.67 mg/dl ≥0.68	6.07(3.01-12.75) 4.68(2.17-10.45) 2.73(1.22-6.21) 参照	7
Schieffer ^[6](CD2)	2017	美国	CD	健康人	233	233	①⑧	≤0.4 mg/dl 0.41~0.50 mg/dl 0.51~0.67 mg/dl ≥0.68	3.60(2.19-5.99) 1.55(0.85-2.81) 1.35(0.76-2.41) 参照	7
Tian ^[11]	2018	中国武汉	UC	健康人	170	200	①⑧	<8.14 μmol/L 8.14~11.01 mg/dl 11.02~14.77 mg/dl >14.77	2.56(1.54-4.25) 2.42(1.44-4.07) 1.52(0.97-2.51) 参照	7
陈影影^[12]	2018	中国徐州	UC	肠镜无异常者	27/28	38/37	①③	-	-	6
蒋传林^[13]	2018	中国武汉	CD	健康人	50/30	92/68	①⑧	<7.63 μmol/L 7.63~11.00 μmol/L 11.01~14.72 μmol/L >14.72	4.86(1.87-10.75) 3.14(1.38-8.44) 2.82(0.56-3.78) 参照	7
Su^[14]	2019	中国广西	CD	健康人	47/24	82/43	①②③	-	-	9
Shi ^[15]	2019	中国西安	UC	健康人	47/53	68/72	①②③④⑤⑧	<8.3 μmol/L 8.3~11.1 μmol/L 11.1~14.472 μmol/L ≥14.472	5.14(2.32-11.39) 2.69(1.23-5.90) 1.99(0.90-4.39) 参照	7
Zhao ^[16](UC)	2019	中国南京	UC	健康人	124/87	134/121	①④⑤⑥⑦	-	-	8
Zhao ^[16](CD)	2019	中国南京	CD	健康人	169/73	134/121	①④⑤⑥⑦	-	-	8
王春莹^[17]	2020	中国西安	UC	健康人	58/32	56/34	①②③⑥	-	-	6
谭丽^[18]	2020	中国吉林	UC	健康人	189/172	43/68	①③	-	-	7
Zhang^[19]	2020	中国南京	UC	健康人	264/184	190/118	①④⑤⑦	-	-	7
Zhou^[7]	2022	中国四川	CD	健康人	66/76	125/114	①⑥	-	-	7
刘奇^[20]	2022	中国河南	UC	肠镜无异常者	28/30	32/33	①③	-	-	6
黄冠华^[21]	2022	中国河南	UC	健康人	31/23	28/22	①②③⑥	-	-	6

图2 IBD组与对照组STB水平比较的森林图

Fig. 2 Forest plot for comparison of STB level between IBD group and control group

表2 IBD组与对照组STB水平比较的亚组分析结果

Tab. 2 Subgroup analysis of comparison of STB level between IBD group and control group

分组方法	亚组	研究数量	异质性(I²)	SMD(95%CI)	P值
疾病类型	UC	11	79.2%	-0.63(-0.79~-0.47)	<0.01
	CD	7	94.9%	-1.05(-1.43~-0.68)	<0.01
研究国家	美国	4	93.3%	-0.49(-0.59~-0.39)	<0.01
	中国	13	0.0%	-0.89(-1.15~-0.63)	<0.01
	捷克	1	0.0%	-0.94(-1.19~-0.69)	<0.01
对照组人群	健康人	16	92.3%	-0.78(-0.98~-0.58)	<0.01
	肠镜检查无异常者	2	0.0%	-1.02(-1.29~-0.76)	<0.01
NOS评分	6分	4	0.0%	-0.93(-1.09~-0.76)	<0.01
	7分	11	90.0%	-0.65(-0.85~-0.44)	<0.01
	≥8分	3	97.1%	-1.24(-2.01~-0.47)	0.002

图3 IBD活动期与缓解期STB水平比较的森林图

Fig. 3 Forest plot for comparison of STB levels of patients in active stage and remission stage

图4 IBD不同严重程度STB水平比较的森林图

Fig. 4 Forest plot for comparison of STB levels in different severities of IBD

图5 IBD患者STB水平与ESR相关性的森林图

Fig. 5 Forest plot of correlation between STB level and ESR in IBD patients

图6 IBD患者STB水平与CRP相关性的森林图

Fig. 6 Forest plot of correlation between STB level and CRP in IBD patients

图7 IBD患者STB水平与临床评分相关性的森林图

Fig. 7 Forest plot of correlation between STB level and clinical score of IBD patients

图8 IBD患者STB水平与Hb相关性的森林图

Fig. 8 Forest plot of correlation between STB level and Hb in IBD patients

图9 低水平STB发生IBD风险的OR值的森林图

Fig. 9 Forest plot of OR of IBD risk in low level STB

图10 所有研究的剪补法分析图

Fig. 10 Trim-and-fill method for all studies

图11 所有研究的敏感性分析——逐一剔除法

Fig. 11 Sensitivity analysis of all studies--step-wise rejection method

图12 分析低水平STB发生IBD的风险时纳入研究的敏感性分析——逐一剔除法

Fig. 12 Sensitivity analysis of all studies when analyzing the risk of IBD in low level STB--step-wise rejection method

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