Meta-analysis of clinical significance of serum total bilirubin level in inflammatory bowel disease

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

Abstract

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

CLC Number:

R574

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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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2023.08.001

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

Figures/Tables 14

Fig. 1 Flow chart of document screening

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

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

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

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

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

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

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

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

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

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

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

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

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

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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