关键词: 肝硬化, 乙型肝炎, 生物学标记, 诊断, 纤维化, 无创肝纤维化模型

Abstract: Background　In recent years，intensive studies in chronic hepatitis B have yielded many noninvasive predictive models to substitute liver biopsy for fibrosis assessment and follow-up.However，the biomarkers required in some noninvasive models are limited in clinical use due to challenges in clinical measurement.Meanwhile，the diagnostic value of the models is also lack of large-scale clinical verification.Objective　To compare the values of six noninvasive fibrotic models of APRI，FIB-4，Forns，HB-F，APGA，and Hui in predicting significant hepatic fibrosis and cirrhosis in chronic hepatitis B patients，to acquire a simple feasible model with the highest diagnostic efficacy for clinical popularization.Methods　Two hundred and twenty-one patients with chronic hepatitis B recruited from the Affiliated Hospital of Southwest Medical University during June 2013 to December 2018 were analyzed retrospectively.All of them underwent liver biopsy，and had routine blood，biochemical and prothrombin time tests within four subsequent weeks.According to the Metavir scoring system，the degree of liver fibrosis of the patients was classified into three groups：F01（n=78，Metavir score=0-1），F23（n=98，Metavir score=2-3），and F4（n=45，Metavir score=4）.Significant fibrosis was defined as Metavir score≥2，cirrhosis was defined as Metavir score=4.Then the scores of six models of noninvasive index（APRI，FIB-4，Forns，HB-F，APGA and Hui ） were calculated.The area under the ROC curve（AUC） analyses of these models in diagnosing significant fibrosis and cirrhosis were performed in patients with ALT ≥ 2ULN or ALT< 2ULN，respectively.Results　 There was significant difference in the scores of six models among the three groups（P<0.05）.The scores of all the models were found to be positively with the severity of liver fibrosis（P<0.05）.For patients with ALT ≥ 2ULN，the AUCs of six models to predict significant fibrosis were 0.836 for APRI，0.738 for FIB-4，0.807 for Forns，0.836 for HB-F，0.912 for APGA，and 0.819 for Hui.The AUCs of APRI，FIB-4，Forns，HB-F，APGA and Hui for predicting cirrhosis were 0.732，0.705，0.789，0.784，0.811 and 0.863，respectively.For patients with ALT< 2ULN，the AUCs of APRI，FIB-4，Forns，HB-F，APGA and Hui were 0.790，0.811，0.825，0.768，0.820，0.787，respectively for predicting significant fibrosis，and 0.815，0.872，0.892，0.857，0.863，0.881 for assessing cirrhosis，respectively.The value of APGA in predicting significant fibrosis in patients with ALT ≥2ULN：when the cutoff value was determined as >0.955，39 of the 42 cases with a APGA score >0.955 were identified with significant fibrosis（Metavir score≥2）；when the cutoff value was determined as >1.005，32 cases with a APGA score >1.005 had significant fibrosis（Metavir score≥2）.The value of APGA in predicting cirrhosis in patients with ALT ≥2ULN：when the cutoff value was determined as >0.955，13 of the 42 cases with a APGA score >0.955 were identified with cirrhosis（Metavir score=4）；when the cutoff value was determined as >1.265，6 of the 7 cases with a APGA score >1.265 had cirrhosis（Metavir score=4）.The value of APGA in predicting significant fibrosis in patients with ALT<2ULN：when the cutoff value was determined as >0.815，93 of the 132 cases with a APGA score >0.955 were identified with significant fibrosis（Metavir score≥2）；when the cutoff value was determined as >1.005，45 of the 47 cases with a APGA score >1.005 were identified with significant fibrosis（Metavir score≥2）.The value of APGA in predicting cirrhosis in patients with ALT<2ULN：when the cutoff value was determined as >0.935，28 of the 70 cases with a APGA score >0.935 were identified with cirrhosis（Metavir score=4）；when the cutoff value was determined as >1.155，3 of the 16 cases with a APGA score >1.155 were diagnosed with cirrhosis（Metavir score=4）.Conclusion　The APGA model has a higher efficacy in diagnosing both significant hepatic fibrosis and cirrhosis for chronic hepatitis B patients with ALT ≥ 2ULN or ALT< 2ULN.Moreover，the measurement of APGA is simple and easy，so the model deserves extensive clinical promotion.

Key words: Liver cirrhosis, Hepatitis B, Biological markers, Diagnosis, Fibrosis, Noninvasive evaluation model of liver fibrosis