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红细胞分布宽度与血小板计数比值评估代谢相关脂肪性肝病及肝硬化的价值分析
DOI: 10.3969/j.issn.1001-5256.2022.04.013
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：白一彤负责研究设计，数据收集，资料分析，撰写论文；白一彤、林连捷、裴冬梅参与文章的修改并最后定稿。
Value of red blood cell distribution width-to-platelet ratio in evaluating metabolic-associated fatty liver disease and liver cirrhosis
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摘要:
目的 评估红细胞分布宽度与血小板计数比值(RPR指数)在评价代谢相关性脂肪性肝病患者严重程度及预测脂肪肝相关肝硬化中的临床意义。 方法 选取2019年1月—2020年6月中国医科大学附属盛京医院收治的代谢相关性脂肪性肝病患者192例(A组)、脂肪肝相关肝硬化患者210例(B组)、同时期于本院体检中心健康体检的对照组206例(C组)。对研究对象进行一般测量、血细胞分析、血生化检测及腹部CT检查，并通过公式计算RPR、APRI、FIB-4指数。方差齐的计量资料3组间比较采用单因素方差分析，两两比较采用SNK法；方差不齐的计量资料3组间比较采用Kruskal -Wallis H检验，两两比较采用Mann-Whitney U检验；计数资料组间比较采用χ2检验，采用受试者工作特征曲线(ROC曲线)分析各变量预测肝硬化的准确性。 结果 3组间两两比较，RDW-SD、Alb、CREA、BMI、RPR以及APRI差异均有统计学意义(P值均＜0.001)。WBC、PLT、ALT、AST、DBil、BUN以及FIB-4在A组与B组比较，差异均有统计学意义(P值均＜0.05)。腰围、空腹血糖在A组分别与B组、C组比较时，差异均有统计学意义(P值均＜0.001)。针对RPR指数，对轻、中、重度代谢相关性脂肪性肝病3组间进行两两比较，差异均有统计学意义(P值均＜0.05)。最后对RPR、APRI、FIB-4三种无创模型预测脂肪肝相关肝硬化的诊断效能进行ROC曲线分析，AUC分别为0.932、0.815、0.877。 结论 RPR指数在肝病的不同阶段存在差异，随着脂肪肝的加重，RPR指数逐渐增高，并且对脂肪肝相关肝硬化的预警价值高于APRI和FIB-4指数。 Abstract:Objective To investigate the clinical significance of red blood cell distribution width-to-platelet ratio (RPR index) in evaluating the severity of metabolic-associated fatty liver disease and predicting fatty liver-associated cirrhosis. Methods A total of 192 patients with metabolic-associated fatty liver disease and 210 patients with fatty liver-associated cirrhosis who were admitted to Shengjing Hospital of China Medical University from January 2019 to June 2020 were enrolled as group A and group B, respectively, and 206 individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group (group C). All subjects underwent general measurement, blood cell analysis, blood biochemical test, and abdominal CT examination, and related formulas were used to calculate RPR, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index. A one-way analysis of variance was used for comparison of continuous data with homogeneity of variance between groups, and the SNK method was used for comparison between two groups; the Kruskal-Wallis H test was used for comparison of continuous data with heterogeneity of variance between groups, and the Mann-Whitney U test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups; the receiver operating characteristic (ROC) curve was used to analyze the accuracy of the prediction of liver cirrhosis. Results There were significant differences in red blood cell distribution width-standard deviation, albumin, creatinine, body mass index, RPR, and APRI between any two groups (all P < 0.001), and there were significant differences in white blood cell count, platelet count, alanine aminotransferase, aspartate aminotransferase, direct bilirubin, blood urea nitrogen, and FIB-4 between group A and group B (all P < 0.05). There were significant differences in waist circumference and fasting blood glucose between groups A and B and between groups A and C (all P < 0.001). There was a significant difference in RPR between any two groups of the mild, moderate, and severe metabolic-associated fatty liver disease groups (all P < 0.05). In terms of diagnostic efficiency, the three noninvasive models RPR, APRI, and FIB-4 had an area under the ROC curve of 0.932, 0.815, and 0.877, respectively, in predicting fatty liver-associated cirrhosis. Conclusion There is a difference in RPR index between different stages of liver disease, and RPR index gradually increases with the aggravation of metabolic-associated fatty liver disease. RPR index has a higher value than APRI and FIB-4 in the warning of fatty liver-associated cirrhosis. -
图 1 RDW-SD、PLT、RPR指数预测脂肪肝相关肝硬化的ROC曲线
Figure 1. ROC curve of RDW-SD, PLT and RPR index in predicting fatty liver related cirrhosis
图 2 3种无创模型预测脂肪肝相关肝硬化的ROC曲线
Figure 2. ROC curve of non-invasive models predicting fatty liver related cirrhosis
表 1 纳入患者的临床数据比较
Table 1. Comparison of clinical data of patients
变量 A组(n=192) B组(n=210) C组(n=206) 统计值 P值 男/女(例) 101/91 115/95 99/107 χ2=1.943 0.379 年龄(岁) 49.82±8.68 49.36±7.98 49.49±8.57 F=0.158 0.854 WBC(×109/L) 6.10(4.70~7.54) 3.55(2.54~4.74)1) 5.93(5.14~6.63) H=216.061 ＜0.001 PLT(×109/L) 236.00(171.00~291.00) 89.00(60.50~127.00)1) 234.00(216.00~253.25) H=429.452 ＜0.001 RDW-SD(fL) 42.30(39.88~48.00) 53.10(49.80~58.30)1) 40.70(39.60~42.15)1)2) H=336.315 ＜0.001 Alb(g/L) 37.80(32.10~41.70) 29.80(27.38~32.93)1) 43.60(41.29~46.03)1)2) H=378.093 ＜0.001 ALT(U/L) 22.50(13.75~36.00) 26.00(17.00~41.50)1) 22.00(15.75~31.00) H=14.133 ＜0.001 AST(U/L) 21.00(15.00~29.75) 27.50(18.00~52.00)1) 20.53(15.59~30.42) H=27.270 ＜0.001 DBil(μmol/L) 9.30(7.00~14.70) 18.95(13.35~26.00)1) 11.08(8.98~13.46) H=161.010 ＜0.001 CREA(μmol/L) 57.20(37.15~74.95) 65.80(54.90~86.00)1) 63.02(53.82~74.20)1)2) H=33.449 ＜0.001 BUN(mmol/L) 4.00(2.99~5.02) 5.57(4.23~7.48)1) 4.17(3.61~4.81) H=98.987 ＜0.001 CRP(mg/L) 6.38(5.33~7.78) 6.54(5.24~7.68) 6.43(5.38~7.98) H=0.420 0.809 空腹血糖(mmol/L) 6.38(5.43~9.23) 5.54(4.92~6.59)1) 5.49(5.11~6.13)1) H=48.550 ＜0.001 BMI(kg/m2) 26.14±4.59 23.29±3.581) 21.77±3.231)2) F=66.620 ＜0.001 腰围(cm) 88.1±9.2 84.4±12.51) 82.8±10.41) F=12.960 ＜0.001 注：与A组比较，1)P＜0.01；与B组比较，2)P＜0.01。 
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表 2 MAFLD组、肝硬化组及健康组3种无创模型参数比较
Table 2. Comparison of parameters of three non-invasive models among MAFLD group, cirrhosis group and healthy group
变量 A组 B组 C组 H值 P值 RPR 0.19(0.16~0.25) 0.61(0.41~0.95)1) 0.15(0.11~0.20)1)2) 384.398 ＜0.001 APRI 0.35(0.26~0.59) 1.21(0.79~1.85)1) 0.30(0.23~0.43)1)2) 362.650 ＜0.001 FIB-4 1.07(0.74~1.48) 4.93(3.13~7.23)1) 0.95(0.76~1.21) 460.801 ＜0.001 注：与A组比较，1)P＜0.01；与B组比较，2)P＜0.01。
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表 3 轻、中、重度MAFLD患者RPR指数比较
Table 3. Comparison of RPR index among mild, moderate and severe MAFLD patients
组别 例数 RPR 轻度组 64 0.14(0.15~0.18) 中度组 70 0.18(0.16~0.20)1) 重度组 58 0.22(0.19~0.27)1)2) H值 96.638 P值 ＜0.001 注：与轻度组比较，1)P＜0.01；与中度组比较，2)P＜0.01。
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表 4 RDW-SD、PLT、RPR指数诊断肝硬化效能分析
Table 4. Efficiency analysis of RDW-SD, PLT and RPR indexes in diagnosing liver cirrhosis
无创诊断模型 AUC 95%CI Cut-off 敏感度(%) 特异度(%) P值 RDW-SD 0.833 0.801~0.866 0.563 4 79.17 77.17 ＜0.000 1 PLT 0.799 0.764~0.834 0.521 6 76.92 75.24 ＜0.000 1 RPR 0.932 0.910~0.951 0.814 0 83.97 97.43 ＜0.000 1
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表 5 3种无创诊断模型诊断肝硬化效能分析
Table 5. Three efficacy analysis of non-invasive diagnostic models in the diagnosis of liver cirrhosis
无创诊断模型 AUC 95%CI Cut-off 敏感度(%) 特异度(%) P值 RPR 0.932 0.910~0.951 0.814 0 83.97 97.43 ＜0.000 1 APRI 0.815 0.783~0.845 0.537 9 71.47 82.32 ＜0.000 1 FIB-4 0.877 0.849~0.902 0.646 9 81.09 83.60 ＜0.000 1
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