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FibroTouch、FibroScan及ARFI在原发性胆汁性胆管炎相关肝纤维化中的诊断价值
DOI: 10.3969/j.issn.1001-5256.2021.04.019
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：王民负责研究实施，资料分析，撰写论文；罗文萍、张冠华参与收集数据，修改论文；赵新颜负责病理读片；马红、田瑛负责课题制定及指导；王宇负责拟定写作思路，指导撰写文章并最后定稿。
Diagnostic value of FibroTouch, FibroScan, and acoustic radiation force impulse for liver fibrosis in patients with primary biliary cholangitis
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摘要:
目的 评估FibroTouch与FibroScan、声辐射力脉冲成像(ARFI)对原发性胆汁性胆管炎(PBC)患者肝纤维化程度的诊断效能。 方法 回顾性纳入2014年9月—2018年10月在首都医科大学附属北京友谊医院行肝穿刺活检明确诊断为PBC的患者。采用METAVIR评分系统评估肝纤维化和炎症程度。在肝活检1周内分别应用瞬时弹性成像(FibroTouch和FibroScan)和ARFI技术检测肝脏硬度值(LS)；以病理结果作为金标准，采用受试者工作特征曲线下面积(AUC)比较3种超声弹性成像技术对PBC肝纤维化的诊断价值，并分析其影响因素；采用Youden指数计算不同程度肝纤维化的诊断界值。多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Bonferroni法校正P值。采用Spearman进行相关性分析，采用多重线性回归模型进行多因素分析。 结果 研究共纳入68例PBC患者，其中肝纤维化F0、F1、F2、F3和F4分别为13、15、18、12和10例。FibroTouch获得的LS(FT-LS)、FibroScan获得的LS(FS-LS)和ARFI获得的LS (ARFI-LS)与肝纤维化程度均呈强正相关(r值分别为0.798、0.782和0.742，P值均＜0.001)。FT-LS诊断F≥2、F≥3、F=4 AUC分别为0.922、0.881、0.926，对应的cut-off值分别为10.5、15.8和17.5 kPa；FS-LS诊断F≥2、F≥3、F=4 AUC分别为0.918、0.878、0.939，对应的cut-off值分别为10.1、12.9和18.2 kPa；ARFI-LS诊断F≥2、F≥3、F=4 AUC分别为0.904、0.869、0.928，对应的cut-off值分别为1.45、1.83和2.08 m/s。3种超声成像技术对各期纤维化程度的诊断差异无统计学意义(P＞0.05)。多因素分析结果显示，FT-LS的影响因素有肝纤维化程度(β=0.399，P＜0.001)、TBil水平(β=0.466，P＜0.001)和PTA(β=-0.195，P=0.020)；FS-LS的影响因素有肝纤维化程度(β=0.370，P＜0.001)、AST(β=0.450，P＜0.001)、PTA(β=-0.303，P=0.001)和ALP(β=-0.187，P=0.042)；而ARFI-LS的影响因素有肝纤维化程度(β=0.489，P＜0.001)、AST(β=0.467，P＜0.001)和PLT(β=-0.188，P=0.028)。 结论 FibroTouch与FibroScan和ARFI在诊断PBC肝纤维化程度的效能相似，特别是对显著纤维化(F≥2)和肝硬化(F=4)具有较高的诊断效能，可作为诊断PBC患者肝纤维化程度的可靠手段。 Abstract:Objective To investigate the diagnostic efficiency of FibroTouch, FibroScan, and acoustic radiation force impulse (ARFI) for liver fibrosis in patients with primary biliary cholangitis (PBC). Methods A retrospective analysis was performed for the patients who underwent liver biopsy and were then diagnosed with PBC in Beijing Friendship Hospital, Capital Medical University, from September 2014 to October 2018, and the METAVIR scoring system was used to evaluate the degree of liver fibrosis and inflammation. Within 1 week after liver biopsy, FibroTouch, FibroScan, and ARFI were used to measure liver stiffness (LS); with pathological results as the gold standard, the area under the ROC curve (AUC) was used to compare the value of FibroTouch, FibroScan, and ARFI in the diagnosis of liver fibrosis in PBC patients, and related influencing factors were analyzed; Youden index was used to calculate the cut-off values of LS for different degrees of liver fibrosis. The Kruskal-Wallis H test was used for comparison between multiple groups, and P value corrected by the Bonferroni method was used for further comparison between two groups. A Spearman correlation analysis was performed, and a multiple linear regression model was used for multivariate analysis. Results A total of 68 patients with PBC were enrolled in the study, among whom 13 had F0 liver fibrosis, 15 had F1 liver fibrosis, 18 had F2 liver fibrosis, 12 had F3 liver fibrosis, and 10 had F4 liver fibrosis. LS obtained by FibroTouch (FT-LS), LS obtained by FibroScan (FS-LS), and LS obtained by ARFI (ARFI-LS) were strongly positively correlated with the degree of liver fibrosis (r=0.798, 0.782, and 0.742, all P < 0.001). FT-LS had AUCs of 0.922, 0.881, and 0.926, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.5 kPa, 15.8 kPa, and 17.5 kPa, respectively; FS-LS had AUCs of 0.918, 0.878, and 0.939, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.1 kPa, 12.9 kPa, and 18.2 kPa, respectively; ARFI-LS had AUCs of 0.904, 0.869, and 0.928, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 1.45 m/s, 1.83 m/s, and 2.08 m/s, respectively. There was no significant difference in diagnosing the same stage of liver fibrosis between FibroTouch, FibroScan, and ARFI (P > 0.05). The multivariate analysis showed that degree of liver fibrosis (β=0.399, P < 0.001), total bilirubin (β=0.466, P < 0.001), and prothrombin time activity (β=-0.195, P=0.020) were influencing factors for FT-LS; degree of liver fibrosis (β=0.370, P < 0.001), aspartate aminotransferase (β=0.450, P < 0.001), prothrombin time activity (β=-0.303, P=0.001), and alkaline phosphatase (β=-0.187, P=0.042) were influencing factors for FS-LS; degree of liver fibrosis (β=0.489, P < 0.001), aspartate aminotransferase (β=0.467, P < 0.001), and platelet count (β=-0.188, P=0.028) were influencing factors for ARFI-LS. Conclusion FibroTouch has similar efficiency to FibroScan and ARFI in the diagnosis of liver fibrosis in PBC patients, with relatively high diagnostic efficiency for significant liver fibrosis (F≥2) and liver cirrhosis (F=4), and therefore, it can be used as a reliable method for the diagnosis of liver fibrosis in PBC patients. -
Key words:
- Liver Cirrhosis, Biliary /
- Liver Cirrhosis /
- Elasticity Imaging Techniques /
- Diagnosis
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表 1 68例PBC患者的临床基本特征
指标 参数 男/女(例) 8/60 年龄(岁) 51.5(44.3~58.8) BMI(kg/m2) 22.7(20.3~24.8) ALT(U/L) 44(27~75) AST(U/L) 58.9(34.0~95.9) ALP(U/L) 198.0(117.3~334.3) GGT(U/L) 162.0(78.8~260.8) TBil(μmol/L) 16.11(11.88~24.93) Alb(g/L) 36.8(34.1~40.8) Cr(mmol/L) 58.5(52.6~65.3) PLT(×109/L) 178.5(99.8~236.3) PTA(%) 98.4(98.3~112.4) 肝纤维化分期[例(%)] F0 13(19.1) F1 15(22.1) F2 18(26.5) F3 12(17.6) F4 10(14.7) 
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表 2 不同肝纤维化分期的FT-LS、FS-LS和ARFI-LS水平
指标 F0 F1 F2 F3 F4 H值 P值 FT-LS(kPa) 5.5(4.6~7.5) 8.0(7.0~10.5) 13.7(11.3~16.1) 16.9(11.7~25.4) 43.2(19.9~51.2) 43.242 ＜0.001 FS-LS(kPa) 5.6(4.9~8.0) 7.0(6.5~8.3) 11.9(8.8~15.0) 15.1(9.5~29.9) 34.4(24.9~46.1) 42.110 ＜0.001 ARFI-LS(m/s) 1.27(1.09~1.57) 1.35(1.19~1.53) 1.81(1.55~2.08) 1.92(1.86~2.19) 2.42(2.15~2.61) 38.798 ＜0.001
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表 3 FT-LS、FS-LS和ARFI-LS对PBC肝纤维化的诊断效能
纤维化分期 AUC(95%CI) cut-off值 敏感度 特异度 F≥2 FT-LS 0.922(0.831~0.973) 10.5 kPa 0.900 0.857 FS-LS 0.918(0.826~0.971) 10.1 kPa 0.800 0.929 ARFI-LS 0.904(0.808~0.962) 1.45 m/s 0.950 0.714 F≥3 FT-LS 0.881(0.780~0.947) 15.8 kPa 0.727 0.913 FS-LS 0.878(0.776~0.945) 12.9 kPa 0.818 0.869 ARFI-LS 0.869(0.765~0.939) 1.83 m/s 0.909 0.804 F=4 FT-LS 0.926(0.836~0.975) 17.5 kPa 0.900 0.879 FS-LS 0.939(0.853~0.982) 18.2 kPa 0.900 0.914 ARFI-LS 0.928(0.838~0.976) 2.08 m/s 1.000 0.845
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