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五种肝硬化无创诊断方法对代偿期乙型肝炎肝硬化患者中医证型的诊断价值分析
DOI: 10.3969/j.issn.1001-5256.2022.01.016
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: 于中杰负责课题设计，资料分析，撰写论文；冯蕾心、刘建鹏、王晗笑参与收集数据，修改论文；赵文霞负责拟定思路，指导撰写文章并定稿。
Value of five noninvasive diagnostic methods for liver cirrhosis in diagnosis of traditional Chinese medicine syndrome types in patients with compensated hepatitis B cirrhosis
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摘要:
目的 探讨5种肝硬化无创诊断[FibroScan肝脏硬度值(LSM值)、AST和PLT比值指数(APRI)、肝纤维化4因子指数(FIB-4)、GGT-PLT比值(GPR)、红细胞体积分布宽度-PLT比值(RPR)]在乙型肝炎肝硬化代偿期中与中医证型的相关性。 方法 回顾性分析2017年1月—2020年1月河南中医药大学第一附属医院确诊为乙型肝炎肝硬化代偿期的327例患者临床相关资料，分为肝郁脾虚证(n=160)、肝胆湿热证(n=84)、肝肾阴虚证(n=13)、脾肾阳虚证(n=5)、瘀血阻络证(n=65)，采集临床相关资料以及血常规、肝功能、LSM值、肝胆脾胰彩超等信息，并对患者进行中医辨证分型，建立APRI、FIB-4、GPR、RPR模型。符合正态分布的计量资料多组间均数比较用单因素方差分析，进一步两两比较采用LSD-t法；不符合正态分布的计量资料多组间比较用多个独立样本Kruskal-Wallis H秩和检验，采用Kruskal-Wallis单因素ANOVE(k样本)进行多重比较；采用二元logistic回归分析进行进中医证型与肝硬化无创诊断的关系；使用受试者工作特征曲线(ROC曲线)评价5种肝硬化无创诊断方法预测乙型肝炎肝硬化代偿期中医证型的诊断能力。 结果 logistic回归分析结果显示，在肝胆湿热证中，AST(OR=1.981，95%CI：1.8225~2.139，P＜0.05)、LSM(OR=2.002，95%CI：1.840~2.160，P＜0.05)是代偿期乙型肝炎肝硬化的影响因素；在肝郁脾虚证中，门静脉宽度(OR=4.402，95%CI：4.050~4.754，P＜0.05)、LSM值(OR=3.901，95%CI：3.589~4.213，P＜0.05]、APRI[OR=1.891，95%CI：1.740~2.042，P＜0.05]、FIB-4(OR=1.845，95% CI：1.697~1.993，P＜0.05)是代偿期乙型肝炎肝硬化的影响因素；在瘀血阻络证中，LSM值(OR=2.465，95%CI：2.268~ 2.662, P＜0.05]、APRI(OR=1.298，95%CI：1.194~1.402, P＜0.05)、FIB-4(OR=1.849，95%CI：1.701~1.997, P＜0.05)是代偿期乙型肝炎肝硬化的影响因素；ROC曲线显示，LSM值与RPR模型评估肝胆湿热证的诊断价值明显优于其他诊断方法；LSM值与FIB-4模型评估肝郁脾虚证的诊断价值明显优于其他诊断方法；5种无创诊断方法均能较好地评估瘀血阻络证。 结论 5种无创诊断方法可对不同证型具有不同评估优势，对乙型肝炎肝硬化代偿期患者中医证型诊断提供参考价值。 Abstract:Objective To investigate the association of five noninvasive diagnostic methods for liver cirrhosis, i.e., liver stiffness measurement (LSM) on FibroScan, aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase-to-platelet ratio (GPR), and red blood cell distribution width-to-platelet ratio (RPR), with traditional Chinese medicine (TCM) syndrome types in patients with compensated hepatitis B cirrhosis. Methods A retrospective analysis was performed for the clinical data of 327 patients who were diagnosed with compensated hepatitis B cirrhosis in The First Affiliated Hospital of Henan University of Chinese Medicine from January 2017 to January 2020, and based on their TCM syndrome type, they were divided into liver depression and spleen deficiency group with 160 patients, liver-gallbladder damp-heat syndrome group with 84 patients, liver-kidney Yin deficiency group with 13 patients, spleen-kidney Yang deficiency group with 5 patients, and blood stasis obstructing the collaterals group with 65 patients. Related data were collected, including clinical data, routine blood test results, liver function, LSM, and color Doppler ultrasound findings of liver, gallbladder, spleen, and pancreas. TCM syndrome differentiation was performed, and the models of APRI, FIB-4, GPR, and RPR were established. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the multiple independent samples Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between multiple groups, and the one- way Kruskal-Wallis ANOVA (k-sample) was used for multiple comparison; the binary logistic regression analysis was used to investigate the association between TCM syndrome types and non-invasive diagnosis of liver cirrhosis; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of five noninvasive methods for predicting TCM syndrome type in compensated hepatitis B cirrhosis. Results The logistic regression analysis showed that in the liver-gallbladder damp-heat syndrome group, aspartate aminotransferase OR=1.981, 95%CI: 1.8225-2.139, P < 0.05), and LSM (OR=2.002, 95%CI: 1.840-2.160, P < 0.05) were influencing factors for compensated hepatitis B cirrhosis; in the liver depression and spleen deficiency group, portal vein width (OR=4.402, 95%CI: 4.050-4.754, P < 0.05), LSM (OR=3.901, 95%CI: 3.589-4.213, P < 0.05), APRI (OR=1.891, 95%CI: 1.740-2.042, P < 0.05), and FIB-4 (OR=1.845, 95%CI: 1.697-1.993, P < 0.05) were influencing factors for compensated hepatitis B cirrhosis; in the blood stasis obstructing the collaterals group, LSM (OR=2.465, 95%CI: 2.268-2.662, P < 0.05), APRI (OR=1.298, 95%CI: 1.194-1.402, P < 0.05), and FIB-4 (OR=1.849, 95%CI: 1.701-1.997, P < 0.05) were influencing factors for compensated hepatitis B cirrhosis. The ROC curve analysis showed that LSM and RPR had a significantly better diagnostic value than the other methods in evaluating liver-gallbladder damp-heat syndrome, and LSM and FIB-4 had a significantly better diagnostic value than the other methods in evaluating liver depression and spleen deficiency; all five noninvasive diagnostic methods had a good value in evaluating the syndrome of blood stasis obstructing the collaterals. Conclusion The five noninvasive diagnostic methods have their own advantages in evaluating different syndrome types, which provide a reference for the diagnosis of TCM syndrome types in patients with compensated hepatitis B cirrhosis. -
Key words:
- Liver Cirrhosis /
- Hepatitis B /
- TCM syndrome /
- Diagnosis
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表 1 中医证型分布情况
证型 例数 性别 年龄（岁） 男(例) 女(例) 肝郁脾虚证 160 120 40 42.96±10.74 肝胆湿热证 84 60 24 43.17±11.12 肝肾阴虚证 13 8 5 45.46±10.41 脾肾阳虚证 5 4 1 46.60±9.74 瘀血阻络证 65 46 19 47.80±10.92 统计值 χ2=1.569 F=2.451 P值 0.814 0.056 
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表 2 代偿期乙型肝炎肝硬化患者主要中医证型基线资料比较
相关指标 肝郁脾虚证(n=160) 肝胆湿热证(n=84) 瘀血阻络证(n=65) 统计量 P值 PLT(×109/L) 138.00(85.25~177.25) 110.50(92.25~142.75) 44.00(34.00~55.50)1)2) χ2=155.337 ＜0.05 ALT(U/L) 34.00(21.95~43.63) 68.85(48.75~109.43)1) 29.50(17.95~39.75)2) χ2=123.210 ＜0.05 AST(U/L) 28.95(23.60~39.63) 61.40(40.15~94.03)1) 27.60(21.55~38.05)2) χ2=86.659 ＜0.05 Alb(g/L) 44.97±3.13 46.25±3.331) 31.41±2.461)2) F=542.512 ＜0.05 GLB(g/L) 29.04±4.46 28.76±4.71 29.09±4.62 F=0.128 0.88 GGT(U/L) 31.20(20.83~53.13) 39.10(27.33~65.15)1) 27.70(21.70~44.05)2) χ2=13.079 ＜0.05 门静脉主干宽度(mm) 12.79±0.76 12.18±0.991) 13.40±0.581)2) F=43.373 ＜0.05 LSM值(kPa) 16.00(13.40~18.08) 18.65(16.63~25.00)1) 24.40(22.30~26.50)1)2) χ2=131.312 ＜0.05 APRI 1.10(0.62~1.35) 1.30(0.88~2.00)1) 1.55(1.26~2.31)1) χ2=54.280 ＜0.05 FIB-4 1.90(1.38~2.74) 2.66(1.99~3.54)1) 6.19(4.66~8.37)1)2) χ2=129.893 ＜0.05 GPR 0.67(0.27~1.18) 0.81(0.49~1.27)1) 1.52(0.94~2.46)1)2) χ2=57.485 ＜0.05 RPR 0.37±0.16 0.39±0.10 1.10±0.341)2) F=351.219 ＜0.05 注：与肝郁脾虚证相比，1)P＜0.05；与肝胆湿热证相比, 2)P＜0.05。
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表 3 各无创诊断评估肝郁脾虚证比较
无创诊断方法 AUC(95%CI) cut-off值 敏感度(%) 特异度(%) 阳性预测值 阴性预测值 阳性似然比 阴性似然比 LSM值 0.982(0.955~0.995) 0.875 98.12 89.33 95.2 95.7 9.20 0.02 APRI 0.899(0.853~0.934) 0.629 86.87 76.00 88.5 73.1 3.62 0.17 FIB-4 0.950(0.913~0.974) 0.776 85.62 92.00 95.8 75.0 10.70 0.16 GPR 0.618(0.553~0.680) 0.303 55.63 74.67 82.4 44.1 2.20 0.59 RPR 0.752(0.692~0.806) 0.533 61.25 92.00 94.2 52.7 7.66 0.42
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表 4 各无创诊断评估肝胆湿热证比较
无创诊断方法 AUC(95%CI) cut-off值 敏感度(%) 特异度(%) 阳性预测值 阴性预测值 阳性似然比 阴性似然比 LSM值 0.922(0.868~0.958) 0.806 95.24 85.33 87.9 94.1 6.49 0.06 APRI 0.834(0.767~0.888) 0.570 80.95 76.00 79.1 78.1 3.37 0.25 FIB-4 0.848(0.783~0.900) 0.536 86.90 66.67 74.5 82.0 2.61 2.61 GPR 0.844(0.778~0.896) 0.553 72.62 82.67 82.4 72.9 4.19 0.33 RPR 0.958(0.914~0.983) 0.777 85.71 92.00 92.3 85.2 10.71 0.16
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表 5 各无创诊断评估瘀血阻络证比较
无创诊断方法 AUC(95%CI) cut-off值 敏感度(%) 特异度(%) 阳性预测值 阴性预测值 阳性似然比 阴性似然比 LSM值 0.969(0.925~0.991) 0.893 100.00 89.33 89.0 100.0 9.37 0.00 APRI 0.895(0.831~0.940) 0.731 98.46 74.67 77.1 98.2 3.89 0.02 FIB-4 0.949(0.899~0.979) 0.845 93.85 90.67 89.7 94.4 10.05 0.07 GPR 0.941(0.888~0.973) 0.765 93.85 82.67 82.4 93.9 5.41 0.07 RPR 0.935(0.880~0.969) 0.893 100.00 89.33 89.0 100.0 9.37 0.00
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