非酒精性脂肪性肝病肝纤维化进展中胃肠激素的变化水平

朱沪敏; 刘旭东; 黄露; 李品桦; 吴铁雄; 庞华珍

doi:10.3969/j.issn.1001-5256.2021.10.021

非酒精性脂肪性肝病肝纤维化进展中胃肠激素的变化水平

DOI: 10.3969/j.issn.1001-5256.2021.10.021

1.
广西中医药大学研究生学院，南宁 530000
2.
广西中医药大学附属瑞康医院肝病科，南宁 530000

基金项目:

广西科技攻关项目 (GK AB18221009);

广西一流学科建设课题 (2019XK139);

广西中医药大学岐黄工程高层次人才团队培育项目 (2021007)

详细信息

通信作者:
刘旭东，lxdlhx@163.com

中图分类号: R575.5
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出版历程
- 收稿日期: 2021-03-02
- 录用日期: 2021-03-23
- 出版日期: 2021-10-20

Expression levels of gastrointestinal hormones in the progression of liver fibrosis in patients with nonalcoholic fatty liver disease

1.
Graduate School, Guangxi University of Chinese Medicine, Nanning 530000, China
2.
Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530000, China

Research funding:

Guangxi Key Science and Technology Program (GK AB18221009);

Guangxi First-class Discipline Construction Project (2019XK139);

Project of High-level Talent Team Cultivation in Qihuang Program of Guangxi University of Chinese Medicine (2021007)

摘要

摘要: 目的探讨非酒精性脂肪性肝病(NAFLD)肝纤维化进展中胃肠激素水平的变化，为消化系统功能损伤提供依据。方法选取2018年10月—2020年6月在广西中医药大学附属瑞康医院门诊就诊及病房住院治疗的NAFLD患者326例，采用FibroTouch进行肝脏弹性值(LSM)检测，按照有无肝纤维化分为无肝纤维化组(A组，LSM＜7.3 kPa，n=161)和肝纤维化组(B组，LSM≥7.3 kPa，n=165)。根据不同纤维化程度，进一步分为F0~1组(LSM＜7.3 kPa)、F2组(7.3 kPa≤LSM＜9.7 kPa)、F2~3组(9.7 kPa≤LSM＜12.4 kPa)、F3~4组(12.4 kPa≤LSM＜17.5 kPa)、F4组(LSM≥17.5 kPa)。收集患者的年龄、性别、肝功能指标、胃肠激素指标。计量资料符合正态分布组间比较采用独立样本t检验和单因素方差分析；不符合正态分布组间比较采用非参数Mann-Whitney U检验和Kruskal-Wallis H检验。应用Spearman分析LSM值与肝功能指标的相关性。结果 A组与B组患者肝功能、胃肠激素指标比较，ALT(Z=-3.778, P＜0.001)、AST(Z=-3.320, P=0.001)、GGT(Z=-3.040, P=0.002)、CCK(t=-2.944, P=0.003)、LPS(Z=-2.317, P=0.020)差异均有统计学意义。F0~1组(n=161)、F2组(n=89)、F2~3组(n=46)、F3~4组(n=16)、F4组(n=14) 5组间ALT(χ²=23.113, P＜0.001)、AST(χ²=23.415, P＜0.001)、ALP(χ²=15.962, P=0.003)、GGT(χ²=20.172, P＜0.001)、CCK(F=2.687, P=0.031)比较差异均有统计学意义。LSM值与DBil、ALT、AST、ALP、GGT呈正相关 (r值分别为0.128、0.266、0.225、0.137、0.213，P值均＜0.05)。结论 NAFLD肝纤维化进展能够影响胆囊收缩功能及胃肠功能，检测NAFLD肝纤维化患者血清CCK、LPS水平对胆囊收缩功能及胃肠功能相关的消化系统疾病的早诊早治有重要的临床价值。
- 非酒精性脂肪性肝病 /
- 肝硬化 /
- 胃肠激素类
Abstract: Objective To investigate the changes in gastrointestinal hormones during the progression of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), and to provide a basis for digestive function impairment. Methods A prospective analysis was performed for 326 patients with NAFLD who attended the outpatient service and were hospitalized and treated in Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from October 2018 to June 2020, and FibroTouch was used to measure liver stiffness measurement (LSM). According to the presence or absence of liver fibrosis, they were divided into non-liver fibrosis group (group A, 161 patients with LSM < 7.3 kPa) and liver fibrosis group (group B, 165 patients with LSM ≥7.3 kPa). According to the fibrosis degree, the patients were further divided into F0-1 group (LSM < 7.3 kPa), F2 group (7.3 kPa ≤LSM < 9.7 kPa), F2-3 group (9.7 kPa ≤LSM < 12.4 kPa), F3-4 group (12.4 kPa ≤LSM < 17.5 kPa), and F4 group (LSM ≥17.5 kPa). Related data were collected, including age, sex, liver function parameters, and gastrointestinal hormones. The independent samples t-test and the one-way analysis of variance were used for comparison of normally distributed continuous data between groups, and the nonparametric Mann-Whitney U test and the Kruskal-Wallis H test were used for comparison of non-normally distributed continuous data between groups. A Spearman correlation analysis was used to investigate the correlation between LSM and liver function parameters. Results Comparison of liver function and gastrointestinal hormones showed that there were significant differences between groups A and B in alanine aminotransferase (ALT) (Z=-3.778, P < 0.001), aspartate aminotransferase (AST) (Z=-3.320, P=0.001), gamma-glutamyl transpeptidase (GGT) (Z=-3.040, P=0.002), cholecystokinin (CCK) (t=-2.944, P=0.003), and lipopolysaccharide (LPS) (Z=-2.317, P=0.020). There were significant differences in ALT (χ²=23.113, P < 0.001), AST (χ²=23.415, P < 0.001), ALP (χ²=15.962, P=0.003), GGT (χ²=20.172, P < 0.001), and CCK (F=2.687, P=0.031) between the F0-1 group with 161 patients, the F2 group with 89 patients, the F2-3 group with 46 patients, the F3-4 group with 16 patients, and the F4 group with 14 patients. LSM was positively correlated with direct bilirubin, ALT, AST, alkaline phosphatase, and GGT (r=0.128, 0.266, 0.225, 0.137, and 0.213, all P < 0.05). Conclusion Liver fibrosis progression in NAFLD can affect gallbladder contraction function and gastrointestinal function, and measurement of the serum levels of CCK and LPS has an important clinical value in the early diagnosis and treatment of digestive diseases related to gallbladder contraction function and gastrointe stinal function in NAFLD patients with liver fibrosis.
- Non-Alcoholic Fatty Liver Disease /
- Liver Cirrhosis /
- Gastrointestinal Hormones

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表 1 5组间肝功能及胃肠激素指标比较

指标	F0~1组(n=161)	F2组(n=89)	F2~3组(n=46)	F3~4组(n=16)	F4组(n=14)	统计值	P值
TBil(μmol/L)	11.10(8.00~16.00)	10.70(8.25~14.25)	11.00(7.23~14.90)	12.60(7.43~14.35)	12.60(8.10~26.20)	χ²=1.940	0.773
DBil(μmol/L)	3.10(2.40~4.55)	3.30(2.50~4.30)	3.80(2.88~4.53)	3.80(2.88~4.63)	4.10(3.38~11.75)	χ²=8.739	0.068
IBil(μmol/L)	7.90(5.30~11.45)	7.60(5.50~9.65)	7.55(4.20~11.05)	8.75(5.25~9.45)	7.85(4.58~10.15)	χ²=1.863	0.761
TP(g/L)	73.49±6.16	74.24±5.51	72.29±6.73	74.62±6.21	72.49±10.90	F=0.939	0.441
Alb(g/L)	44.27±4.34	43.89±3.78	44.00±6.46	44.24±3.81	39.54±8.02	F=3.249	0.012
Glb(g/L)	29.30(26.10~31.95)	30.70(27.30~32.75)	29.15(26.38~32.20)	30.10(28.25~35.45)	29.65(26.00~37.78)	χ²=5.464	0.243
ALT(U/L)	25.00(16.50~35.00)	28.00(19.50~45.00)	44.50(23.00~90.00)	31.00(18.25~56.50)	47.50(34.50~76.75)	χ²=23.113	＜0.001
AST(U/L)	22.00(16.50~28.00)	23.00(18.00~32.50)	29.50(23.00~47.50)	26.50(16.50~40.25)	41.00(19.25~70.25)	χ²=23.415	＜0.001
ALP(U/L)	68.00(56.00~80.50)	66.00(57.00~78.50)	77.00(59.75~85.25)	70.50(58.25~102.50)	88.00(69.50~129.00)	χ²=15.962	0.003
GGT(U/L)	34.00(24.00~55.00)	38.00(27.00~57.00)	50.00(35.00~76.00)	37.50(33.00~50.00)	73.00(42.50~224.25)	χ²=20.172	＜0.001
CCK(ng/mL)	49.91±26.19	60.36±25.43	57.16±23.35	56.32±24.68	50.39±26.36	F=2.687	0.031
DAO(U/L)	9.74±2.10	9.42±2.81	9.81±2.64	8.91±2.15	9.18±2.14	F=0.787	0.534
D-LA(mmol/L)	25.59±10.95	23.81±8.61	25.10±12.15	23.21±7.52	25.66±8.97	F=0.557	0.694
G-17(pg/mL)	17.27(13.24~21.71)	17.77(14.10~22.39)	17.56(11.32~21.71)	20.97(13.25~23.13)	18.21(12.36~22.25)	χ²=2.650	0.618
LPS(EU/mL)	463.68(317.24~587.17)	412.40(222.89~533.94)	387.26(212.48~529.82)	411.17(124.25~598.58)	474.39(360.81~626.83)	χ²=7.922	0.094
MTL(pg/mL)	182.75(111.76~256.14)	170.36(110.37~245.35)	169.01(116.54~206.94)	206.01(145.96~243.70)	155.40(104.97~197.02)	χ²=3.819	0.431

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表 2 两组间肝功能指标、胃肠激素指标比较

指标	A组(n=161)	B组(n=165)	统计值	P值
肝功能
TBil(μmol/L)	11.10(8.00~16.00)	10.90(8.15~14.50)	Z=-0.671	0.502
DBil(μmol/L)	3.10(2.40~4.55)	3.50(2.60~4.40)	Z=-1.905	0.057
IBil(μmol/L)	7.90(5.30~11.45)	7.60(5.10~9.65)	Z=-1.358	0.174
TP(g/L)	73.49±6.16	73.58±6.52	t=-0.137	0.891
Alb(g/L)	44.27±4.34	43.58±5.20	t=1.296	0.196
Glb(g/L)	29.30(26.10~31.95)	30.10(27.10~32.70)	Z=-1.677	0.093
ALT(U/L)	25.00(16.50~35.00)	32.00(21.00~57.50)	Z=-3.778	＜0.001
AST(U/L)	22.00(16.50~28.00)	26.00(19.00~36.00)	Z=-3.320	0.001
ALP(U/L)	68.00(56.00~80.50)	69.00(58.50~85.00)	Z=-1.587	0.113
GGT(U/L)	34.00(24.00~55.00)	41.00(29.50~64.50)	Z=-3.040	0.002
胃肠激素
CCK(ng/mL)	49.91±26.19	58.23±24.81	t=-2.944	0.003
DAO(U/L)	9.74±2.10	9.46±2.65	t=1.074	0.284
D-LA(mmol/L)	25.59±10.95	24.26±9.61	t=1.159	0.247
G-17(pg/mL)	17.27(13.24~21.71)	18.31(12.99~22.17)	Z=-0.428	0.668
LPS(EU/mL)	463.68(317.24~587.17)	412.40(222.89~547.73)	Z=-2.317	0.020
MTL(pg/mL)	182.75(111.76~256.14)	171.44(116.49~240.04)	Z=-1.068	0.286

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