LPRI评分在乙型肝炎肝纤维化及肝硬化中的诊断价值

周家玲; 王冰琼; 孙亚朦; 孟彤彤; 武珊珊; 马红; 欧晓娟; 尤红; 贾继东; 吴晓宁

doi:10.3969/j.issn.1001-5256.2022.07.014

LPRI评分在乙型肝炎肝纤维化及肝硬化中的诊断价值

DOI: 10.3969/j.issn.1001-5256.2022.07.014

周家玲^{1, 2},
王冰琼^{1, 2},
孙亚朦^{1, 2},
孟彤彤^{1, 2},
武珊珊²,
马红^{1, 2},
欧晓娟^{1, 2},
尤红^{1, 2},
贾继东^{1, 2},
吴晓宁^{1, 2, , ,}

1.
首都医科大学附属北京友谊医院肝病中心，北京 100050
2.
国家消化系统疾病临床医学研究中心，北京 100050

基金项目:

国家“十二五”科技重大专项课题 (2013ZX10002004);

王宝恩肝纤维化研究基金资助 (CFHPC2022029)

伦理学声明：本研究方案2013年5月经由首都医科大学附属北京友谊医院伦理委员会审批，批号为BJFH-EC/2013-027，所有入组的患者均签署知情同意书。

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。

作者贡献声明：尤红、吴晓宁负责课题设计；贾继东、欧晓娟、马红、吴晓宁、周家玲、孙亚朦、王冰琼、孟彤彤参与数据收集及整理；武珊珊参与分析方法指导；周家玲负责资料分析、撰写论文；吴晓宁、王冰琼负责修改论文。

详细信息

通信作者:
吴晓宁，wuxiaoningbs@126.com

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出版历程
- 收稿日期: 2022-02-10
- 录用日期: 2022-04-02
- 出版日期: 2022-07-20

Application value of liver stiffness measurement-to-platelet ratio index score in diagnosis of hepatitis B liver fibrosis and liver cirrhosis

Jialing ZHOU^{1, 2},
Bingqiong WANG^{1, 2},
Yameng SUN^{1, 2},
Tongtong MENG^{1, 2},
Shanshan WU²,
Hong MA^{1, 2},
Xiaojuan OU^{1, 2},
Hong YOU^{1, 2},
Jidong JIA^{1, 2},
Xiaoning WU^{1, 2
, ,
,}

1.
Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
2.
National Clinical Research Center for Digestive Diseases, Beijing 100050, China

Research funding:

National Science and Technology Major Project (2013ZX10002004);

WBE Liver Fibrosis Foundation (CFHPC2022029)

More Information

Corresponding author: WU Xiaoning, wuxiaoningbs@126.com(ORCID: 0000-0001-5416-712X)

摘要

摘要: 目的肝纤维化程度的评估对于指导慢性乙型肝炎患者治疗及预测预后具有重要意义，本研究旨在评价LPRI评分对乙型肝炎肝纤维化/肝硬化初治人群的诊断价值。方法筛选首都医科大学附属北京友谊医院既往乙型肝炎研究队列2013年6月—2015年9月经肝穿刺确诊的慢性乙型肝炎患者276例。基于患者肝脏硬度测定(LSM)联合PLT计算LPRI评分，以肝脏病理为金标准，评价LPRI评分对于乙型肝炎肝纤维化及肝硬化的诊断价值。不符合正态分布计量资料多组间比较采用Kruskal-Wallis H秩和检验，计数资料组间比较采用χ²检验。各诊断模型与肝穿病理的相关性分析采用Spearman相关分析；通过DeLong法比较多个无创诊断模型(LPRI、LSM、APRI、FIB-4)的受试者工作特征曲线下面积(AUC)及诊断性能。采用Bootstrap方法对LPRI肝纤维化/肝硬化的诊断价值进行内部验证。结果根据肝纤维化程度的不同，分为F0/1组(n=63)、F2/3组(n=118)、F4组(n=95)，3组间Alb、TBil、PLT、LSM、AFP及HBV DNA水平均具有统计学差异(P值均＜0.05)。LPRI评分与肝穿病理有较好的相关性(r=0.501，P＜0.001)；对乙型肝炎显著性肝纤维化(AUC=0.88, 95%CI: 0.83~0.91)的诊断性能优于肝硬化(AUC=0.79, 95%CI: 0.73~0.83)。相比APRI评分和FIB-4指数，LPRI的诊断性能更好(P值均＜0.05)；与LSM联合后，LPRI评分能进一步补充LSM对肝硬化诊断的灵敏度(53%提高至82%)。经约登指数推荐的诊断显著性肝纤维化和肝硬化的LPRI评分界值分别为6.1(灵敏度71%，特异度92%)和6.9(灵敏度81%，特异度66%)。结论 LPRI评分作为一种简易方便的肝纤维化无创诊断指数，在慢性乙型肝炎患者肝纤维化/肝硬化的诊断和分期中有一定的应用价值。
- 乙型肝炎, 慢性 /
- 肝硬化 /
- 诊断
Abstract: Objective To investigate the diagnostic value of liver stiffness measurement-to-platelet ratio index (LPRI) score in previously untreated patients with hepatitis B liver fibrosis/liver cirrhosis, since the evaluation of liver fibrosis degree has great significance in guiding the treatment of chronic hepatitis B patients and predicting their prognosis. Methods A total of 276 chronic hepatitis B patients who were diagnosed by liver biopsy from June 2013 to September 2015 were selected from the hepatitis B study cohort of Beijing Friendship Hospital, Capital Medical University. LPRI score was calculated based on liver stiffness measurement (LSM) and platelet, and the value of LPRI score in the diagnosis of liver fibrosis and liver cirrhosis in hepatitis B patients was evaluated with liver pathology as the gold standard. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was used to investigate the correlation between each diagnostic model and liver biopsy, and the DeLong test was used to compare the area under the ROC curve (AUC) and diagnostic performance of several noninvasive diagnostic models, i.e., LPRI, LSM, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4). The Bootstrap method was used for the internal validation of the value of LPRI score in the diagnosis of liver fibrosis/cirrhosis. Results According to the stage of liver fibrosis, the patients were divided into F0/1 group with 63 patients, F2/3 group with 118 patients, and F4 group with 95 patients, and there were significant differences in albumin, total bilirubin, platelet count, LSM, alpha-fetoprotein, and HBV DNA between the three groups (all P < 0.05). LPRI score was significantly correlated with liver biopsy (r=0.501, P < 0.001); LPRI score had an AUC of 0.88 (95% confidence interval [CI]: 0.83-0.91) in the diagnosis of liver fibrosis and an AUC of 0.79 (95% CI: 0.73-0.83) in the diagnosis of liver cirrhosis, suggesting that the diagnostic performance of LPRI score for significant liver fibrosis was better than that for liver cirrhosis. LPRI had a better diagnostic performance than APRI and FIB-4 (both P < 0.05), and in combination with LSM, LPRI score further supplemented the sensitivity of LSM in the diagnosis of liver cirrhosis, with an increase from 53% to 82%. The cut-off values of LPRI score recommended by Youden index were 6.1 (with a sensitivity of 71% and a specificity of 92%) for significant liver fibrosis and 6.9 (with a sensitivity of 81% and a specificity of 66%) for liver cirrhosis. Conclusion As a simple and convenient noninvasive diagnostic index for liver fibrosis, LPRI score has a certain application value in the diagnosis and staging of liver fibrosis and liver cirrhosis in chronic hepatitis B patients.
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- Diagnosis

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图 1 LPRI、LSM、APRI及FIB-4与METAVIR评分相关关系的箱式图

Figure 1. The box diagram of correlation among LPRI, LSM, APRI, FIB-4 and METAVIR score

下载: 全尺寸图片幻灯片

图 2 不同肝纤维化诊断模型AUC的比较

注：a, 显著肝纤维化组(≥F2, n=213)；b, 肝硬化组(F4, n=95)

Figure 2. Comparison of AUC among different diagnostic models of liver fibrosis and cirrhosis

下载: 全尺寸图片幻灯片

表 1 入组患者的基线特征

Table 1. The baseline characteristics of all enrolled patients

项目	总体(n=276)	F0/1组(n=63)	F2/3组(n=118)	F4组(n=95)	χ²值	P值
人口学数据
年龄(岁)	39.0(31.0~48.0)	37.0(29.0~44.0)	39.0(31.8~46.3)	42.0(32.0~51.0)	2.205	0.332
男性(%)	70.4	66.7	70.3	77.1	146.962	＜0.001
BMI(kg/m²)	23.2(21.0~25.1)	22.9(20.6~24.8)	23.0(21.0~24.7)	24.2 (21.6~26.8)	3.891	0.143
血清生化学检测
ALT(U/L)	60.9(36.0~100.0)	70.9(45.0~109.0)	61.7(35.1~101.0)	57.0(34.0~93.0)	2.737	0.254
AST(U/L)	43.9(31.8~64.0)	43.0(30.2~61.0)	44.0(32.1~66.2)	43.1(31.0~66.5)	0.244	0.885
Alb(g/L)	43.0(39.7~46.3)	44.0(41.0~47.0)	43.1(40.6~46.6)	41.9(37.8~45.5)	8.096	0.017
TBil(μmol/L)	15.5(11.0~24.5)	12.2(10.1~17.8)	13.6(10.7~17.4)	29.0(16.0~50.3)	69.988	＜0.001
PLT(×10⁹/L)	154.5(116.3~192.0)	192.0(161.0~238.0)	154.0(120.0~187.5)	128.0(98.0~163.0)	25.752	＜0.001
LSM(kPa)	11.1(7.5~17.1)	6.8(5.3~8.4)	11.8(8.1~14.9)	17.2(11.3~22.3)	98.493	＜0.001
AFP(ng/mL)	4.1(2.2~9.0)	2.5(1.5~5.0)	5.0(2.8~9.7)	5.8(2.9~17.9)	45.271	＜0.001
病毒学检测
HBV DNA(log IU/mL)	6.3(5.1~7.5)	6.3(5.1~7.4)	6.2(5.0~7.2)	5.9(4.4~6.9)	10.769	0.005

下载: 导出CSV

表 2 不同肝纤维化模型LPRI与LSM、APRI、FIB-4的AUC比较

Table 2. The comparison of AUC between LPRI, LSM, APRI and FIB-4

不同模型比较	≥F2组(n=213)			F4组(n=94)
不同模型比较	△AUC	Z值	P值	△AUC	Z值	P值
LPRI vs LSM	0.010	0.52	0.600	0.010	0.63	0.530
LPRI vs APRI	0.180	6.08	＜0.000 1	0.220	6.40	＜0.000 1
LPRI vs FIB-4	0.132	4.60	＜0.000 1	0.170	5.43	＜0.000 1
注：△AUC，前后两种模型AUC的差值。

下载: 导出CSV

表 3 LPRI评分和LSM的肝纤维化诊断性能

Table 3. The diagnostic performance of LPRI score and LSM in significant fibrosis and cirrhosis

项目	LPRI		LSM		LSM联合LPRI
项目	≥F2组	F4组	≥F2组	F4组	≥F2组	F4组
约登指数推荐界值	6.1	6.9	9.4 kPa	17.0 kPa	-	-
灵敏度(%)	71	81	73	53	79	82
特异度(%)	92	66	88	89	84	65
阳性预测值(%)	95	55	96	71	94	55
阴性预测值(%)	47	87	50	78	54	87

下载: 导出CSV

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