传统非侵入性纤维化模型对慢性乙型肝炎合并代谢相关脂肪性肝病发生显著肝纤维化的诊断价值

Abstract

目的 评价传统非侵入性纤维化模型对慢性乙型肝炎 (CHB) 合并代谢相关脂肪性肝病 (MAFLD) 发生显著肝纤维化的诊断价值。 方法 纳入2014年9月—2020年12月在广东省中医院肝病科行肝脏病理检查且同时符合CHB和MAFLD诊断标准的患者共499例。采用Scheuer评分系统评价肝纤维化程度。呈非正态分布的计量资料组间比较采用Mann－Whitney U检验；采用Spearman对各无创诊断方法与肝脏纤维化程度进行相关性分析；绘制受试者工作特征曲线 (ROC曲线) ，评价FibroScan、GPR、APRI、FIB－4、LPRI对CHB合并MAFLD的诊断价值；利用二元Logistic回归分析构建联合模型，将联合模型与5种指标单独应用时的ROC曲线下面积 (AUC) 进行比较；采用Delong检验对各无创诊断方法进行AUC的两两比较。 结果 无或轻度肝纤维化组 (S0 ~ S1) 198例，显著肝纤维化组 (S≥2) 301例。S≥2组的各项临床指标均高于S0 ~ S1组，其中ALT、AST、GGT、TBil、GPR、FIB－4、APRI、LPRI、LSM差异均有统计学意义 (P值均<0.05) 。Spearman相关性分析结果显示，GPR、FIB－4、APRI、LSM、LPRI与肝脏纤维化分期均呈正相关 (r值分别为0.393、0.414、0.449、0.553、0.580，P值均<0.001) 。ROC曲线分析显示，GPR、FIB－4、APRI、LSM、LPRI单独应用诊断显著性肝纤维化的AUC分别为0.704、0.715、0.740、0.787、0.802；利用二元Logistic回归分析构建GPR、FIB－4、APRI、LSM的联合模型LGAF，LGAF诊断显著性肝纤维化的AUC为0.814；将LGAF分别与GPR、FIB－4、APRI、LSM、LPRI的AUC进行比较，除了与LPRI相比差异无统计学意义以外，其余均有统计学意义 (Z值分别为5.184、4.884、4.117、2.120，P值均<0.05) 。 结论 FibroScan、GPR、APRI、FIB－4、LPRI五项数据模型对CHB合并MAFLD发生显著肝纤维化的诊断价值与CHB合并NAFLD发生显著纤维化的诊断价值相似，对于临床实际无创评估肝纤维化的应用有参考及指导价值。

Alternate abstract:

Objective To investigate the value of traditional noninvasive fibrosis models in the diagnosis of significant liver fibrosis in patients with chronic hepatitis B (CHB) and metabolic associated fatty liver disease (MAFLD). Methods A total of 499 patients who underwent liver pathological examination in Department of Hepatology, Guangdong Provincial Hospital of Traditional Chinese Medicine, from September 2014 to December 2020 and met the diagnostic criteria for CHB and MAFLD were enrolled in this study. The Scheuer scoring system was used to evaluate the degree of liver fibrosis. The Mann－Whitney U test was used for comparison of normally distributed continuous data between groups. A Spearman correlation analysis was used to investigate the correlation of each noninvasive diagnostic method with the degree of liver fibrosis; the receiver operating characteristic (ROC) curve was plotted to investigate the value of FibroScan, gamma－glutamyl transpeptidase－to－platelet ratio (GPR), aspartate aminotransferase－to－platelet ratio index (APRI), fibrosis－4 (FIB－4), and liver stiffness measurement－to－platelet ratio index (LPRI) in the diagnosis of CHB with MAFLD; a binary Logistic regression analysis was used to construct a combined model, and the area under the ROC curve (AUC) was compared between the combined model and the five indicators used alone. The DeLong method was used for comparison of AUC between any two noninvasive diagnostic methods. Results There were 198 patients in the group with no or mild liver fibrosis (S0－S1) and 301 patients in the group with significant liver fibrosis (S≥2). The S≥2 group had higher clinical indicators than the S0－S1 group, with significant differences between the two groups in alanine aminotransferase, aspartate aminotransferase, gamma－glutamyl transpeptidase, total bilirubin, GPR, FIB－4, APRI, LPRI, and liver stiffness measurement (LSM) (all P<0.05). The Spearman correlation analysis showed that GPR, FIB－4, APRI, LSM, and LPRI were positively correlated with the stage of liver fibrosis (r = 0.393, 0.414, 0.449, 0.553, and 0.580, all P<0.001). The ROC curve analysis showed that GPR, FIB－4, APRI, LSM, and LPRI used alone had an AUC of 0.704, 0.715, 0.740, 0.787, and 0.802, respectively, in the diagnosis of significant liver fibrosis. The binary Logistic regression analysis was used to construct a combined LGAF model of GPR, FIB－4, APRI, and LSM, which had an AUC of 0.814 in the diagnosis of significant liver fibrosis. LGAF was compared with GPR, FIB－4, APRI, LSM, and LPRI, respectively, in terms of AUC, and the results showed that there was a significant difference between LGAF and all five indicators except LPRI (Z=5.184, 4.884, 4.117, and 2.120, all P<0.05). Conclusion The five data models of FibroScan, GPR, APRI, FIB－4, and LPRI have a similar value in the diagnosis of significant liver fibrosis in CHB with MAFLD compared with the combined LGAF model, which provides reference and guidance for the application of noninvasive assessment of liver fibrosis in clinical practice.