常见临床指标及无创肝纤维化评分对中国肝病型Wilson病进展期肝纤维化的诊断价值

梁晨; 刘晖; 白洁; 任艳; 王泰龄; 刘念晨; 白丽; 刘霜; 陈煜; 段钟平; 郑素军

doi:10.3969/j.issn.1001-5256.2021.03.014

常见临床指标及无创肝纤维化评分对中国肝病型Wilson病进展期肝纤维化的诊断价值

DOI: 10.3969/j.issn.1001-5256.2021.03.014

梁晨^{1a, 2},
刘晖^1b,
白洁^{1a, 2},
任艳^{1a, 2},
王泰龄³,
刘念晨^{1a, 2},
白丽^{1a, 2},
刘霜^{1a, 2},
陈煜^{1a, 2},
段钟平^{1a, 2},
郑素军^{1a, 2, ,}

1a.
首都医科大学附属北京佑安医院肝病中心四科，北京 100069
1b.
首都医科大学附属北京佑安医院病理科，北京100069
2.
肝衰竭与人工肝治疗研究北京市重点实验室，北京 100069
3.
中日友好医院病理科，北京 100029

基金项目:

北京市医院管理局消化内科学科协同发展中心项目 (XXZ0503);

科技创新服务能力建设-高精尖学科建设项目 (11920703)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。

作者贡献声明：梁晨负责资料查阅、写作；刘晖、郑素军负责写作框架设计；梁晨、刘晖、白洁、王泰龄参与数据收集、分析；任艳、刘念晨、白丽负责数据分析；刘霜、陈煜、段钟平、郑素军负责审核结果。

详细信息

作者简介:
梁晨(1996—)，女，主要从事遗传代谢性肝病研究

通信作者:
郑素军，zhengsujun003@126.com

中图分类号: R575.2;R589.9
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- 被引次数: 0
出版历程
- 收稿日期: 2020-09-07
- 录用日期: 2020-10-09
- 出版日期: 2021-03-20

Value of common clinical indices and noninvasive liver fibrosis scores in the diagnosis of advanced liver fibrosis in hepatic-type Wilson's disease in China

Chen LIANG^{1a, 2},
Hui LIU^1b,
Jie BAI^{1a, 2},
Yan REN^{1a, 2},
Tailing WANG³,
Nianchen LIU^{1a, 2},
Li BAI^{1a, 2},
Shuang LIU^{1a, 2},
Yu CHEN^{1a, 2},
Zhongping DUAN^{1a, 2},
Sujun ZHENG^{1a, 2
, ,}

1a.
The Fourth Department of Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
1b.
Department of Pathology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
2.
Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing 100069, China
3.
Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China

摘要

摘要: 目的探讨常见临床指标及无创肝纤维化评分与中国肝病型Wilson病(WD)的关系，及其对进展期肝纤维化的鉴别能力。方法回顾性收集1996年5月—2020年4月于北京佑安医院及中日友好医院诊治的236例中国WD患者临床资料，纳入有肝脏病理且临床资料齐全的肝病型WD患者26例，应用METAVIR评分判断肝纤维化分期，将患者分为进展期肝纤维化(F3期、F4期)和非进展期肝纤维化(F0期、F1期、F2期)两组，计算3种无创肝纤维化评分(Sheth指数、APRI指数、FIB-4指数)，比较两组间上述指数、相关临床指标差异。计量资料两组间比较采用独立样本t检验或Mann-Whitney U秩和检验；计数资料两组间比较采用Fisher检验。应用Spearman秩相关对有差异的指标进一步分析，筛选出与肝纤维化程度相关的临床指标及评分标准，绘制受试者工作特征曲线(ROC曲线)并计算曲线下面积(AUC)。结果本研究患者多在儿童及青少年时期发病，其中有10例(38.5%)患者K-F环为阳性，17例(65%)患者处于进展期肝纤维化阶段。进展期和非进展期肝纤维化患者比较，WBC(Z=-2.102，P=0.036)、Hb(t=-2.860，P=0.009)、PLT(t=-4.053，P＜0.001)、DBil(Z=-2.130，P=0.033)、Alb(t=-2.875，P=0.008)、Sheth指数(Z=-3.369，P=0.001)差异均有统计学意义。WBC、Hb、PLT、Alb水平与WD患者肝纤维化程度呈负相关(r值分别为-0.587、-0.610、-0.656、-0.411，P值均＜0.05)，DBil和Sheth指数与肝纤维化程度呈正相关(r值分别为0.486、0.711，P值均＜0.05)。ROC曲线分析显示，WBC、DBil、Sheth指数、Hb、PLT、Alb的AUC均＞0.7，其中Sheth指数的AUC最大，为0.908，其敏感度和特异度分别为70.6%和100.0%，阳性和阴性预测值分别为100.0%和64.3%。结论 Sheth指数的诊断效能优于其余单一临床指标，对中国肝病型WD进展期肝纤维化有较好的鉴别能力。
- 肝硬化 /
- 肝豆状核变性 /
- 诊断 /
- 中国
Abstract: Objective To investigate the association of common clinical indices and noninvasive liver fibrosis scores with hepatic-type Wilson's disease (WD) in Chinese patients and their ability to identify advanced liver fibrosis. Methods A retrospective analysis was performed for the clinical data of 236 Chinese patients with WD who were diagnosed and treated in Beijing YouAn Hospital and China-Japan Friendship Hospital from May 1996 to April 2020. A total of 26 patients with hepatic-type WD who underwent liver pathological examination and had complete clinical data were enrolled; the METAVIR score was used to determine liver fibrosis stage, and the patients were divided into advanced liver fibrosis (F3 and F4 stages) group and non-advanced liver fibrosis (F0, F1, and F2 stages) groups. Three noninvasive liver fibrosis scores [Sheth index, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index] were calculated for both groups, and the above indices and related clinical indices were compared between the two groups. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the Fisher's exact test was used for comparison of categorical data between two groups. The Spearman rank correlation test was used for further analysis of indices with statistical significance, and the clinical indices and scoring criteria correlated with liver fibrosis degree were screened out; the receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC) was calculated. Results Most of the patients in this study developed the disease in childhood and adolescence, and among these patients, 10 (38.5%) had positive K-F ring and 17 (65%) were in the stage of advanced liver fibrosis. There were significant differences between the advanced liver fibrosis group and the non-advanced liver fibrosis group in white blood cell count (WBC) (Z=-2.102, P=0.036), hemoglobin (Hb) (t=-2.860, P=0.009), platelet count (PLT) (t=-4.053, P < 0.001), direct bilirubin (DBil) (Z=-2.130, P=0.033), albumin (Alb) (t=-2.875, P=0.008), and Sheth index (Z=-3.369, P=0.001). WBC, Hb, PLT, and Alb were negatively correlated with liver fibrosis degree in WD patients (r=-0.587, -0.610, -0.656, and -0.411, all P < 0.05), and DBil and Sheth index were positively correlated with liver fibrosis degree (r=0.486 and 0.711, both P < 0.05). The ROC curve analysis showed that WBC, DBil, Sheth index, Hb, PLT, and Alb had an AUC of > 0.7, among which Sheth index had the largest AUC of 0.908, with a sensitivity of 70.6%, a specificity of 100.0%, a positive predictive value of 100.0%, and a negative predictive value of 64.3%. Conclusion Sheth index has a better diagnostic efficiency than the other clinical indices alone and can well identify advanced liver fibrosis in Chinese patients with hepatic-type WD.
- Liver Cirrhosis /
- Hepatolenticular Degeneration /
- Diagnosis /
- China

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图 1 相关临床指标、Sheth指数对WD进展期肝纤维化诊断的ROC曲线

下载: 全尺寸图片幻灯片

表 1 两组临床指标及无创肝纤维化评分比较

变量	全部患者 (n=26)	进展期纤维化组 (n=17)	非进展期纤维化组 (n=9)	统计值	P值
男/女(例)	14/12	8/9	6/3		0.429
K-F环(有/无或未知，例)	10/16	7/10	3/6		1.000
发病时年龄(岁)	19.77±14.37	20.18±16.34	19.00±10.52	t=0.195	0.847
WBC(×10⁹/L)	4.62(3.94~5.69)	4.14(3.68~5.32)	5.58(4.74~6.31)	Z=-2.102	0.036
Hb(g/L)	135.85±49.94	117.88±26.57	169.78±66.35	t=-2.860	0.009
PLT(×10⁹/L)	157.24±93.75	114.60±61.44	237.78±93.55	t=-4.053	＜0.001
ALT(U/L)	57.30(25.00~197.13)	52.60(23.00~150.00)	191.30(30.65~227.25)	Z=-1.617	0.106
AST(U/L)	68.00(24.40~108.80)	46.30(24.10~125.10)	71.80(25.30~103.30)	Z=-0.081	0.936
TBil(μmol/L)	16.05(10.18~25.78)	17.00(12.55~35.40)	9.70(7.55~23.85)	Z=-1.913	0.056
DBil(μmol/L)	5.45(2.50~9.75)	7.20(3.85~10.40)	2.50(1.20~6.30)	Z=-2.130	0.033
Alb(g/L)	38.30±6.28	36.34±6.61	42.01±3.45	t=-2.875	0.008
GGT(U/L)	74.95(36.38~136.00)	82.00(41.30~139.00)	73.30(27.60~155.55)	Z=-0.296	0.767
ALP(U/L)	162.20(66.75~332.13)	193.90(68.00~333.75)	130.50(65.55~311.25)	Z=-0.189	0.850
Sheth指数	0.89(0.55~1.22)	0.98(0.80~1.59)	0.51(0.45~0.75)	Z=-3.369	0.001
FIB-4指数	3.92(0.80~5.56)	2.62(0.82~4.84)	5.66(0.73~13.88)	Z=-1.644	0.100
APRI指数	0.98(0.59~2.28)	1.72(0.69~3.31)	0.79(0.55~0.98)	Z=-1.913	0.056

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表 2 WD患者临床指标、无创肝纤维化评分与肝纤维化程度的相关性

变量	95%CI	r值	P值
WBC(×10⁹/L)	3.36~9.04	-0.587	0.002
Hb(g/L)	115.67~156.02	-0.610	0.001
PLT(×10⁹/L)	119.37~195.10	-0.656	＜0.001
DBil(μmol/L)	4.66~10.54	0.486	0.012
Alb(g/L)	35.77~40.84	-0.411	0.037
Sheth指数	0.70~1.43	0.711	＜0.001

下载: 导出CSV

表 3 Sheth指数及相关临床指标对WD进展期肝纤维化的诊断效能结果

变量	AUC	P值	预测临界值	敏感度(%)	特异度(%)	阳性预测值(%)	阴性预测值(%)
WBC	0.755	0.036	4.615×10⁹/L	70.6	88.9	92.3	61.5
DBil	0.758	0.033	2.800 μmol/L	88.2	55.6	78.9	71.4
Sheth指数	0.908	0.001	0.905	70.6	100.0	100.0	64.3
Hb	0.889	0.001	137.500 g/L	88.2	88.9	93.7	80.0
PLT	0.869	0.002	172.500×10⁹/L	88.2	77.8	88.2	77.8
Alb	0.781	0.020	41.350 g/L	76.5	77.8	86.7	63.6

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