代谢相关脂肪性肝病肝纤维化危险因素分析及构建预测模型

doi:10.3969/j.issn.1004-583X.2025.05.006

摘要/Abstract

摘要：

目的探讨代谢相关脂肪性肝病(metabolic dysfunction-associated fatty liver disease,MAFLD)肝纤维化发生的相关危险因素,并构建预测肝纤维化的列线图。方法回顾性收集MAFLD患者的人口统计学资料及血生化指标等。根据FibroScan检测肝脏组织硬度值(liver stiffness measure,LSM), 判断患者是否存在肝纤维化。利用logistic回归分析MAFLD肝纤维化的潜在预测指标,并构建列线图模型;通过C指数评估模型的区分能力,通过校准图分析模型的一致性,并通过决策曲线评价模型的临床实用性。结果共纳入MAFLD患者282例,其中97例存在肝纤维化(LSM≥8 kPa),185例为非肝纤维化(LSM<8 kPa)。单因素分析显示,血小板、血小板/白细胞比值(platelet to white blood cell ratio,PWR)、碱性磷酸酶、丙氨酸氨基转移酶、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、γ-氨酸转肽酶、血尿酸(serum uric acid,UA)、同型半胱氨酸(homocysteine,HCY)是发生肝纤维化的影响因素(P<0.05)。多因素logistic回归分析显示PWR(OR=0.921, 95%CI:0.877~0.967,P<0.001)是肝纤维化的保护因素,HCY(OR=1.101, 95%CI:1.032~1.175,P=0.003)、AST(OR=1.021, 95%CI:1.011~1.031,P<0.001)、UA(OR=1.032, 95%CI:1.001~1.066,P=0.048)是肝纤维化的独立危险因素;基于上述因素构建的列线图模型具有良好的区分度(AUC=0.835,95%CI:0.779~0.891),校准曲线提示肝纤维化的预测概率与观测概率一致性较高,临床决策曲线确定列线图在阈值概率内有较高的净获益。结论基于PWR、HCY、AST、UA构建的列线图模型可较好地预测MAFLD肝纤维化相关风险,从而进行早期识别和干预,具有较高的临床应用价值。

关键词: 非酒精性脂肪性肝病, 代谢相关脂肪性肝病, 肝纤维化, 列线图, 危险因素

Abstract:

Objective To explore the related risk factors for the occurrence of liver fibrosis in metabolic dysfunction-associated fatty liver disease (MAFLD), and to construct a nomogram to predict liver fibrosis. Methods Demographic data and blood biochemical indicators of MAFLD patients were retrospectively collected. Liver fibrosis was determined by the liver stiffness measure (LSM) detected via FibroScan. Logistic regression analysis was conducted to identify potential predictive indicators for liver fibrosis in MAFLD, and a nomogram was then created. The discrimination ability, consistency, and clinical applicability of the nomogram were assessed through C-index, calibration plots, and decision curves, respectively. Results A total of 282 MAFLD patients were included. Among them, 97 patients had liver fibrosis (LSM≥8 kPa), and 185 patients did not have liver fibrosis (LSM<8 kPa). Univariate analysis indicated that platelet count (PLT), platelet-to-white blood cell ratio (PWR), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), serum uric acid (UA), and homocysteine (HCY) were influencing factors for liver fibrosis in MAFLD patients (P<0.05). The multivariate Logistic regression analysis revealed that the PWR (OR=0.921, 95%CI: 0.877-0.967, P<0.001) was a protective factor for liver fibrosis, HCY(OR=1.101, 95%CI: 1.032-1.175, P=0.003), AST(OR=1.021, 95%CI: 1.011-1.031, P<0.001), and UA(OR=1.032, 95%CI: 1.001-1.066, P=0.048) were independent risk factors for liver fibrosis in MAFLD patients. The nomogram constructed based on these factors had good discrimination (area under the curve [AUC]=0.835, 95%CI: 0.779-0.891), and the calibration curve indicated that the predicted probability of liver fibrosis was highly consistent with the observed probability. The clinical decision curve determined that the nomogram had a high net benefit within the threshold probability range. Conclusion The nomogram constructed based on PWR, HCY, AST and UA can well predict the risk of liver fibrosis in MAFLD patients, thereby enabling early identification and intervention. It has high clinical application value.

Key words: non-alcoholic fatty liver disease, metabolic dysfunction-associated fatty liver disease, liver fibrosis, nomogram, risk factors

中图分类号:

R575.5

肇雪婷, 白佳雯, 孙军. 代谢相关脂肪性肝病肝纤维化危险因素分析及构建预测模型[J]. 临床荟萃, 2025, 40(5): 417-422.

Zhao Xueting, Bai Jiawen, Sun Jun. Analysis of risk factors for liver fibrosis in metabolic dysfunction-associated fatty liver disease and construction of a nomogram[J]. Clinical Focus, 2025, 40(5): 417-422.

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链接本文: https://lchc.magtechjournal.com/CN/10.3969/j.issn.1004-583X.2025.05.006

https://lchc.magtechjournal.com/CN/Y2025/V40/I5/417

图/表 7

参考文献 21

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组别			例数	年龄 (岁)			性别[例(%)]						BMI[例(%)]								高血压病 [例(%)]	吸烟史 [例(%)]		饮酒史 [例(%)]
组别			例数	年龄 (岁)			男性			女性			正常			超重			肥胖		高血压病 [例(%)]	吸烟史 [例(%)]		饮酒史 [例(%)]
训练集			199	53(42,61)			122.0(61.3)			77.0(38.7)			37(18.6)			67(33.7)			95(47.7)		87(43.7)	63(31.7)		28(14.1)
验证集			83	50(40,60)			43.0(51.8)			40.0(48.2)			15(18.1)			29(34.9)			39(47.7)		31(37.3)	17(20.5)		5(6.02)
χ²/Z值				-0.502			2.177						0.043								0.976	3.600		3.670
P值				0.615			0.140						0.979								0.323	0.058		0.055
组别	HOMA-IR					FPG (mmol/L)			HbA₁c (%)			UA (mmol/L)			WBC (×10⁹/L)			PLT (×10⁹/L)		PWR		ALB (g/L)		ALT (IU/L)
训练集	7.86(4.4,13.8)					9.88(7.10, 13.5)			8.1(6.7, 9.6)			367(300,453)			7.5(6.14,9.05)			231(200,275)		28.98(24.62,36.9)		45(42,47)		44(27,78)
验证集	5.83(4.27, 10.38)					8.72(6.75, 12.76)			7.8(6.4, 9.6)			350(326,435)			7.36(5.89,8.6)			236(211,282)		34.0(41.0,47.0)		45(41,47)		55(29,83)
χ²/Z值	-1.938					-1.345			-0.944			-0.004			-1.122			-0.863		-2.351		-0.438		-0.758
P值	0.053					0.179			0.345			0.997			0.262			0.388		0.072		0.628		0.448
组别		AST (IU/L)			HCY (μmol/L)			GGT (IU/L)			ALP (IU/L)			TC (mmol/L)			TG (mmol/L)				HLD-C (mmol/L)		LDL-C (mmol/L)
训练集		30(22,62)			12(9,17)			55(36,88)			82(66,95)			5.24(4.28,6.22)			2.27(1.53,3.91)				1.11(0.98,1.33)		3.27(2.60,3.93)
验证集		37(23,59)			11(9,16)			54(36,91)			82(65,101)			5.37(4.3,6.06)			2.64(1.79,3.40)				1.20(1.04,1.33)		3.37(2.71,4.07)
χ²/Z值		-0.543			-0.969			-0.315			-0.196			-0.357			-1.203				-1.469		-0.839
P值		0.587			0.333			0.753			0.844			0.753			0.229				0.142		0.402

组别			例数	年龄 (岁)			性别[例(%)]						BMI[例(%)]								高血压病 [例(%)]	吸烟史 [例(%)]		饮酒史 [例(%)]
组别			例数	年龄 (岁)			男性			女性			正常			超重			肥胖		高血压病 [例(%)]	吸烟史 [例(%)]		饮酒史 [例(%)]
训练集			199	53(42,61)			122.0(61.3)			77.0(38.7)			37(18.6)			67(33.7)			95(47.7)		87(43.7)	63(31.7)		28(14.1)
验证集			83	50(40,60)			43.0(51.8)			40.0(48.2)			15(18.1)			29(34.9)			39(47.7)		31(37.3)	17(20.5)		5(6.02)
χ²/Z值				-0.502			2.177						0.043								0.976	3.600		3.670
P值				0.615			0.140						0.979								0.323	0.058		0.055
组别	HOMA-IR					FPG (mmol/L)			HbA₁c (%)			UA (mmol/L)			WBC (×10⁹/L)			PLT (×10⁹/L)		PWR		ALB (g/L)		ALT (IU/L)
训练集	7.86(4.4,13.8)					9.88(7.10, 13.5)			8.1(6.7, 9.6)			367(300,453)			7.5(6.14,9.05)			231(200,275)		28.98(24.62,36.9)		45(42,47)		44(27,78)
验证集	5.83(4.27, 10.38)					8.72(6.75, 12.76)			7.8(6.4, 9.6)			350(326,435)			7.36(5.89,8.6)			236(211,282)		34.0(41.0,47.0)		45(41,47)		55(29,83)
χ²/Z值	-1.938					-1.345			-0.944			-0.004			-1.122			-0.863		-2.351		-0.438		-0.758
P值	0.053					0.179			0.345			0.997			0.262			0.388		0.072		0.628		0.448
组别		AST (IU/L)			HCY (μmol/L)			GGT (IU/L)			ALP (IU/L)			TC (mmol/L)			TG (mmol/L)				HLD-C (mmol/L)		LDL-C (mmol/L)
训练集		30(22,62)			12(9,17)			55(36,88)			82(66,95)			5.24(4.28,6.22)			2.27(1.53,3.91)				1.11(0.98,1.33)		3.27(2.60,3.93)
验证集		37(23,59)			11(9,16)			54(36,91)			82(65,101)			5.37(4.3,6.06)			2.64(1.79,3.40)				1.20(1.04,1.33)		3.37(2.71,4.07)
χ²/Z值		-0.543			-0.969			-0.315			-0.196			-0.357			-1.203				-1.469		-0.839
P值		0.587			0.333			0.753			0.844			0.753			0.229				0.142		0.402

变量	回归系数	标准误	OR值	95%CI		Z值	P值
变量	回归系数	标准误	OR值	下限	上限	Z值	P值
年龄	-0.005	0.011	0.995	0.974	1.017	-0.463	0.644
性别	0.137	0.305	1.146	0.631	2.084	0.447	0.655
高血压病	0.529	0.299	1.698	0.945	3.050	1.771	0.076
吸烟史	0.053	0.317	1.054	0.566	1.962	0.166	0.868
饮酒史	0.524	0.412	1.689	0.753	3.786	1.272	0.203
BMI	0.544	0.407	1.723	0.776	3.825	1.336	1.336
PLT	-0.010	0.003	0.990	0.984	0.996	-3.662	<0.001
WBC	0.071	0.065	1.073	0.945	1.219	1.090	0.276
PWR	-0.090	0.021	0.914	0.877	0.952	-4.385	<0.001
ALB	-0.032	0.028	0.969	0.917	1.024	-1.115	0.265
ALP	0.014	0.006	1.014	1.002	1.026	2.369	0.018
ALT	0.012	0.003	1.013	1.007	1.019	3.703	<0.001
AST	0.022	0.005	1.023	1.013	1.033	4.550	<0.001
GGT	0.009	0.003	1.009	1.003	1.015	2.867	0.004
TC	-0.099	0.097	0.906	0.749	1.095	-1.017	0.309
TG	-0.025	0.037	0.975	0.907	1.049	-0.667	0.505
HDL-C	-0.753	0.464	0.471	0.190	1.169	-1.624	0.104
LDL-C	-0.054	0.142	0.947	0.717	1.251	-0.380	0.704
UA	0.030	0.013	1.030	1.004	1.057	2.349	0.019
HbA₁c	0.056	0.075	1.057	0.913	1.225	0.739	0.460
FPG	0.045	0.037	1.046	0.973	1.125	1.235	0.217
HOMA-IR	0.020	0.017	1.020	0.987	1.055	1.144	0.253
HCY	0.113	0.030	1.119	1.056	1.187	3.811	<0.001

变量	回归系数	标准误	OR值	95%CI		Z值	P值
变量	回归系数	标准误	OR值	下限	上限	Z值	P值
年龄	-0.005	0.011	0.995	0.974	1.017	-0.463	0.644
性别	0.137	0.305	1.146	0.631	2.084	0.447	0.655
高血压病	0.529	0.299	1.698	0.945	3.050	1.771	0.076
吸烟史	0.053	0.317	1.054	0.566	1.962	0.166	0.868
饮酒史	0.524	0.412	1.689	0.753	3.786	1.272	0.203
BMI	0.544	0.407	1.723	0.776	3.825	1.336	1.336
PLT	-0.010	0.003	0.990	0.984	0.996	-3.662	<0.001
WBC	0.071	0.065	1.073	0.945	1.219	1.090	0.276
PWR	-0.090	0.021	0.914	0.877	0.952	-4.385	<0.001
ALB	-0.032	0.028	0.969	0.917	1.024	-1.115	0.265
ALP	0.014	0.006	1.014	1.002	1.026	2.369	0.018
ALT	0.012	0.003	1.013	1.007	1.019	3.703	<0.001
AST	0.022	0.005	1.023	1.013	1.033	4.550	<0.001
GGT	0.009	0.003	1.009	1.003	1.015	2.867	0.004
TC	-0.099	0.097	0.906	0.749	1.095	-1.017	0.309
TG	-0.025	0.037	0.975	0.907	1.049	-0.667	0.505
HDL-C	-0.753	0.464	0.471	0.190	1.169	-1.624	0.104
LDL-C	-0.054	0.142	0.947	0.717	1.251	-0.380	0.704
UA	0.030	0.013	1.030	1.004	1.057	2.349	0.019
HbA₁c	0.056	0.075	1.057	0.913	1.225	0.739	0.460
FPG	0.045	0.037	1.046	0.973	1.125	1.235	0.217
HOMA-IR	0.020	0.017	1.020	0.987	1.055	1.144	0.253
HCY	0.113	0.030	1.119	1.056	1.187	3.811	<0.001

变量	回归系数	标准误	OR值	95%CI		Z值	P值
变量	回归系数	标准误	OR值	下限	上限	Z值	P值
PWR	-0.082	0.025	0.921	0.877	0.967	-3.308	<0.001
AST	0.021	0.005	1.021	1.011	1.031	3.760	<0.001
UA	0.032	0.016	1.032	1.001	1.066	1.981	0.048
HCY	0.096	0.033	1.101	1.032	1.175	2.964	0.003