多元判别分析评分与FIB-4诊断慢性HBV感染者肝纤维化程度的准确性比较

刘宏宇; 李小婷; 江建宁; 金超; 蔡彩莲; 王可杉; 零芳蓬; 范冰凌; 苏明华

doi:10.12449/JCH250412

多元判别分析评分与FIB-4诊断慢性HBV感染者肝纤维化程度的准确性比较

DOI: 10.12449/JCH250412

广西医科大学第一附属医院感染性疾病科，南宁 530021

基金项目:

国家自然科学基金 (82160123)

伦理学声明：本研究方案于2024年8月27日经由广西医科大学第一附属医院伦理委员会审批，批号：2024-E610-01，患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：刘宏宇负责文章结构设计、文章撰写及数据分析；金超、蔡彩莲、王可杉、零芳蓬、范冰凌负责数据收集；李小婷负责数据整理；江建宁、苏明华负责指导文章撰写、修改并最后定稿。

详细信息

通信作者:
苏明华， smh9292@163.com （ORCID： 0000-0001-7831-6580）

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出版历程
- 收稿日期: 2024-09-18
- 录用日期: 2024-10-19
- 出版日期: 2025-04-25

Accuracy of multivariate discriminant analysis versus fibrosis-4 in evaluating the liver fibrosis degree in patients with chronic HBV infection

Department of Infectious Diseases，The First Affiliated Hospital of Guangxi Medical University，Nanning 530021，China

Research funding:

National Natural Science Foundation of China (82160123)

More Information

Corresponding author: SU Minghua， smh9292@163.com （ORCID： 0000-0001-7831-6580）

摘要

摘要: 目的比较多元判别分析评分（MDA）和FIB-4对HBV感染者肝纤维化程度的诊断准确性，探讨MDA作为诊断疾病进展指标的可能性。方法纳入2010年4月—2024年4月在广西医科大学第一附属医院行肝活检的HBV感染者263例，收集患者临床资料。根据病理结果，分为非显著纤维化组（F<2，n=126）和显著纤维化组（F≥2，n=137），分析MDA、FIB-4与肝纤维化程度的相关性，比较两者评估显著性肝纤维化的准确性；62例患者完成随访，根据末次随访时是否发展为肝硬化分为进展组（n=21）与未进展组（n=41），分析并比较MDA、FIB-4诊断疾病进展的效能。符合正态分布的计量资料两组间比较采用成组t检验；非正态分布的计量资料两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Bonferroni法。计数资料的组间比较采用χ²检验。采用Spearman相关法进行相关性分析。采用Wilcoxon符号秩和检验对基线与随访终点的资料进行配对分析；二元Logistic回归分析患者进展为肝硬化的影响因素。利用受试者操作特征曲线（ROC曲线）分析指标的诊断效能，ROC曲线下面积（AUC）的比较采用Z检验，采用配对χ²检验比较两指标的灵敏度、特异度和准确率。结果 FIB-4、MDA与肝纤维化程度的相关系数分别为0.378、-0.325（P值均<0.001）。FIB-4诊断显著性肝纤维化的AUC、灵敏度、特异度、阳性预测值、阴性预测值及准确率分别为0.688、64.96%、68.87%、67.42%、63.36%、65.40%，最佳截断值为1.01；MDA诊断显著性肝纤维化AUC、灵敏度、特异度、阳性预测值、阴性预测值及准确率分别为0.653、52.55%、78.57%，72.73%、60.37%、65.02%，最佳截断值为0.29；MDA的灵敏度低于FIB-4（P=0.004），但特异度较高（P=0.001）。基线时，进展组患者年龄较未进展组大（t=2.611，P=0.011）。在进展组，与基线时相比，随访终点时FIB-4升高、MDA降低（P值均<0.001）；未进展组无明显变化（P值均>0.05）。多因素Logistic回归分析结果显示，AST（OR=0.940，95%CI：0.885～0.998，P<0.05）、MDA（OR=0.445，95%CI：0.279～0.710，P<0.001）是疾病进展的独立影响因素；对于诊断疾病进展为肝硬化，MDA的AUC为0.893，最佳截断值为-0.01。结论 MDA诊断显著性肝纤维化的准确性与FIB-4相当；MDA<-0.01对于诊断肝纤维化发展为肝硬化有较高的准确性，有助于减少临床上肝活检的需要。
- 乙型肝炎病毒 /
- 肝纤维化 /
- 诊断
Abstract: Objective To investigate the accuracy of multiple discriminant analysis （MDA） versus fibrosis-4 （FIB-4） in assessing liver fibrosis degree in patients with HBV infection， as well as the possibility of MDA as an indicator for disease progression. Methods A total of 263 patients with HBV infection who underwent liver biopsy in The First Affiliated Hospital of Guangxi Medical University from April 2010 to April 2024 were included， and their clinical data were collected. According to the results of pathological examination， they were divided into non-significant fibrosis group （F<2） with 126 patients and significant fibrosis group （F≥2） with 137 patients. The correlation of MDA and FIB-4 with liver fibrosis degree was analyzed， and MDA and FIB-4 were compared in terms of their accuracy in assessing significant liver fibrosis. A total of 62 patients completed follow-up， and according to the presence or absence of progression to liver cirrhosis at the last follow-up visit， they were divided into progressive group with 21 patients and non-progressive group with 41 patients； the efficacy of MDA and FIB-4 in diagnosing disease progression was analyzed and compared. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data. The Spearman’s correlation coefficient was used for correlation analysis. The Wilcoxon signed rank sum test was used for the analysis of baseline data and data at the end of follow-up， and the binary Logistic regression analysis was used to investigate the influencing factors for progression to liver cirrhosis. The receiver operating characteristic （ROC） curve was used to investigate the diagnostic efficacy of indicators， the Z-test was used for comparison of the area under the ROC curve （AUC）， and the paired chi-square test was used for comparison of the sensitivity， specificity， and accuracy of the two indicators. Results The correlation coefficient between FIB-4 and liver fibrosis degree was 0.378， while the correlation coefficient between MDA and liver fibrosis degree was -0.325 （both P<0.001）. FIB-4 had an AUC of 0.688， a sensitivity of 64.96%， a specificity of 68.87%， a positive predictive value of 67.42%， a negative predictive value of 63.36%， an accuracy of 65.40%， and a cut-off value of 1.01， while MDA had an AUC of 0.653， a sensitivity of 52.55%， a specificity of 78.57%， a positive predictive value of 72.73%， a negative predictive value of 60.37%， an accuracy of 65.02%， and a cut-off value of 0.29， suggesting that compared with FIB-4， MDA had a lower sensitivity （P=0.004） and a higher specificity （P=0.001）. The progressive group had a significantly higher age than the non-progressive group at baseline （t=2.611， P=0.011）. For the progressive group， there was an increase in FIB-4 and a reduction in MDA from baseline to the end of follow-up （both P<0.001）， while the non-progressive group showed no significant changes （both P>0.05）. The multivariate Logistic regression analysis showed that aspartate aminotransferase （odds ratio ［OR］=0.940， 95% confidence interval ［CI］： 0.885‍ ‍—‍ ‍0.998， P<0.05） and MDA （OR=0.445， 95%CI： 0.279‍ ‍—‍ ‍0.710， P<0.001） were independent influencing factors for disease progression. MDA had an AUC of 0.893 and an optimal cut-off value of -0.01 in diagnosing the disease progression of liver cirrhosis. Conclusion MDA has a comparable accuracy to FIB-4 in the diagnosis of significant liver fibrosis， and MDA<-0.01 has a high accuracy in diagnosing the progression of liver fibrosis to liver cirrhosis， which can help to reduce the need for liver biopsy in clinical practice.
- Hepatitis B Virus /
- Hepatic Fibrosis /
- Diagnosis

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图 1 不同纤维化程度FIB-4及MDA中位数分布

Figure 1. Median distribution of FIB-4 and MDA in patients with different degrees of fibrosis

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表 1 显著性与非显著性肝纤维化HBV感染者临床资料比较

Table 1. Clinical data of HBV infected patients with significant and non-significant fibrosis

临床特征	显著肝纤维化组（n=137）	非显著肝纤维化组（n=126）	统计值	P值
性别［例（%）］			χ²=0.180	0.671
女	37（27.01）	37（29.37）
男	100（72.99）	89（70.63）
HBeAg［例（%）］			χ²=0.013	0.911
阳性	40（29.20）	36（28.57）
阴性	97（70.80）	90（71.43）
抗病毒［例（%）］			χ²=5.946	0.015
否	98（71.53）	72（57.14）
是	39（28.47）	54（42.86）
lg HBV DNA（IU/mL）	4.20（2.70～5.72）	3.42（2.70～5.68）	Z=-1.022	0.307
年龄（岁）	39.00（35.00～47.00）	38.00（32.00～47.00）	Z=-1.570	0.118
Alb（g/L）	41.10（38.30～43.30）	41.65（39.80～43.95）	Z=-1.810	0.071
ALT（g/L）	32.00（22.00～47.00）	28.00（19.25～38.00）	Z=-2.110	0.035
AST（g/L）	31.00（24.00～43.00）	26.00（20.00～32.00）	Z=-4.070	<0.001
ALP（U/L）	69.00（59.00～90.00）	65.00（55.00～81.75）	Z=-1.580	0.115
PLT（10⁹/L）	174.20（139.10～226.70）	214.25（180.18～246.53）	Z=-4.740	<0.001
FIB-4	1.18（0.81～1.92）	0.86（0.66～1.18）	Z=-5.270	<0.001
MDA	0.11（-2.71～3.59）	2.65（0.43～4.50）	Z=-4.280	<0.001
炎症分级^1）［例（%）］			χ²=60.020	<0.001
G0	8（5.84）	6（4.76）
G1	31（22.63）	80（63.49）
G2	49（35.77）	35（27.78）
G3	42（30.66）	5（3.97）
G4	7（5.11）	0
METAVIR评分^2）［例（%）］			χ²=263.000	<0.001
F0	0	46（36.51）
F1	0	80（63.49）
F2	63（45.99）	0
F3	48（35.04）	0
F4	26（18.98）	0
注：1）根据病理结果将组织炎症程度分为G0～G4级；2）METAVIR评分用于评价肝脏纤维化程度，由轻到重分为F0～F4。

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表 2 FIB-4、MDA在不同METAVIR评分患者中的比较

Table 2. Comparison of FIB-4 and MDA in patients with different METAVIR scores

组别	例数	FIB-4	MDA
F0组	46	0.86（0.63～1.11）	2.52（0.81～4.53）
F1组	80	0.86（0.66～1.21）	2.75（0.33～4.56）
F2组	63	1.04（0.73～1.45）	1.29（-1.08～4.88）
F3组	48	1.27（0.89～2.13）^1）4）	0.06（-3.02～3.68）^1）4）
F4组	26	1.75（0.95～3.04）^1）2）4）	-3.02（-8.55～-0.64）^{1）2）3）4）}
H值		-40.584	-36.030
P值		P<0.001	P<0.001
注：与F1组比较，1）P<0.05；与F2组比较，2）P<0.05；与F3比较，3）P<0.05；与F0比较，4）P<0.05。

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表 3 FIB-4、MDA对显著性肝纤维化的诊断效能

Table 3. Diagnostic efficacy of FIB-4 and MDA for significant liver fibrosis

血清学模型	AUC（95%CI）	最佳截断值	灵敏度（%）	特异度（%）	阳性预测值（%）	阴性预测值（%）	准确率（%）	P值
FIB-4	0.688（0.625～0.752）	1.01	64.96	68.87	67.42	63.36	65.40	<0.001
MDA	0.653（0.586～0.719）	0.29	52.55	78.57	72.73	60.37	65.02	<0.001

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表 4 进展组与未进展组中FIB-4和MDA变化情况

Table 4. Changes in FIB-4 and MDA in the progression group and non-progression group

组别	例数	基线	随访终点	差值及其95%CI	Z值	P值
进展组	21
FIB-4		1.27（0.85～1.45）	1.89（1.67～2.68）	0.86（0.53～1.79）	4.015	<0.001
MDA		1.74（0.07～2.75）	-2.20（-4.72～-0.20）	-3.72（-6.37～-2.42）	3.945	<0.001
未进展组	41
FIB-4		0.84（0.70～1.16）	1.01（0.70～1.33）	0.07（-0.07～0.19）	0.978	0.328
MDA		2.86（0.65～4.45）	3.31（0.86～4.78）	0.35（-0.76～1.51）	0.667	0.505
注：差值指随访终点与基线的差值。

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表 5 慢性HBV感染者进展为肝硬化二元logistic回归分析

Table 5. Binary Logistic regression analysis for progression of chronic HBV infection to cirrhosis

自变量	单因素分析				多因素分析
自变量	β值	SE	P值	OR（95%CI）	β值	SE	P值	OR（95%CI）
男性	-0.85	0.65	0.196	0.429（0.119～1.546）
规律抗病毒	-0.60	0.68	0.375	0.549（0.146～2.066）
HBeAg阳性	-0.98	0.83	0.238	0.374（0.073～1.918）
随访结束时年龄	0.05	0.03	0.086	1.053（0.993～1.117）
Alb	-0.25	0.09	0.003	0.778（0.658～0.919）
ALT	0.02	0.01	0.047	1.024（1.001～1.049）	0.08	0.04	0.050	1.083（1.000～1.172）
AST	0.04	0.02	0.030	1.046（1.004～1.088）	-0.06	0.03	0.044	0.940（0.885～0.998）
ALP	0.02	0.01	0.104	1.023（0.995～1.052）
PLT	-0.03	0.01	<0.001	0.969（0.953～0.986）
FIB-4	2.55	0.74	<0.001	12.855（2.998～55.113）
MDA	-0.54	0.15	<0.001	0.585（0.438～0.781）	-0.81	0.24	<0.001	0.445（0.279～0.710）

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表 6 FIB-4、MDA在诊断疾病进展中的准确性

Table 6. The accuracy of FIB-4 and MDA in diagnosing disease progression

血清学模型	AUC（95%CI）	最佳截断值	灵敏度（%）	特异度（%）	阳性预测值（%）	阴性预测值（%）	准确率（%）	P值
FIB-4	0.871（0.781～0.961）	1.37	85.71	80.49	68.00	89.19	80.65	<0.001
MDA	0.893（0.813～0.974）	-0.01	80.95	85.37	73.91	89.74	83.87	<0.001

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