低病毒载量HBeAg阴性慢性HBV感染者肝组织学特点及不同诊断指标对非活动携带的诊断价值

目的探讨低病毒载量HBeAg阴性慢性HBV感染者的肝组织学特点,评价不同临床标准对非活动HBsAg携带(IC)的诊断价值。方法选择HBV DNA4.3lg IU/mL、ALT2×正常值上限(ULN)、HBeAg阴性的慢性HBV感染者为研究对象,观察其肝组织特点,炎症活动指数(HAI)≤3或病变轻微定义为病理学的IC。临床诊断标准:A组为2015年中国指南标准(ALT正常,HBV DNA2.3 lg IU/mL),B组为2015年亚太与美国指南标准(ALT正常,HBV DNA3.3 lg IU/mL),C组为ALT2×ULN、HBV DNA2.3 lg IU/mL,D组为ALT2×ULN,HBV DNA3.3 lg IU/mL)。以肝组织学结果为"金标准"评价四组IC临床诊断标准的价值。结果 171例患者入选,其中男性125例,女46例,年龄22~69岁,平均(45.5±4.2)岁。HAI 1~11分,平均(4.3±2.1)分,其中≤3分者94例,占55.0%;纤维化积分(S)0~4分,平均(2.0±1.6)分,其中0~1分101例,占59.1%。不同临床IC诊断标准筛选的病例与病理IC的符合率没有显著差异。四种筛查方法的约登指数为0.08~0.11,AUC为0.544~0.558,判断IC的价值有限。所有入选病例中符合中国、亚太与欧美指南IC临床诊断的患者,仅有50%~60%符合病理IC,而临床非IC的患者中,有33.3%~51.4%符合病理学的IC诊断。结论低病毒载量HBeAg阴性慢性HBV感染者中有50%~60%的患者符合病理的IC诊断,而临床非IC的患者中,有33.3%~51.4%符合病理学的IC诊断。若以病理结果为IC诊断的"金标准",现有指南推荐的临床标准诊断IC的效率不高,判断价值有限,亚太与美国指南(2015)略有优势。

Diagnostic value of different criteria for inactive HBsAg carriers and liver histological features in HBeAg-negative chronic hepatitis B patients with low HBV DNA level

Objective To investigate the histological characteristics of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with low viral load and to evaluate the diagnostic value of different criteria for inactive hepatitis B surface antigen (HBsAg) carriers (IC).Methods HBeAg-negative CHB patients with HBV DNA ＜ 4.3 log10 IU/mL and alanine aminotransferase (ALT) ＜ 2 the upper limit of normal (ULN) were enrolled in the study.All patients underwent liver biopsy.Patients with histological activity index (HAI) ≤ 3 or mild liver pathological damage were defined as pathologically IC.Four clinical criteria were applied in the study.For diagnosis of IC,group A was based on the 2015 Chinese guidelines (normal ALT,HBV DNA ＜ 2.3 log11 IU/mL),group B was on the 2015 APASL or AASLD guidelines (normal ALT,HBV DNA ＜ 3.3 log10 IU/mL),group C was on ALT ＜ 2 ULN and HBV DNA ＜ 2.3 log10 IU/mL,and Group D was on normal ALT and HBV DNA ＜ 3.3 log10 IU/mL.Diagnostic value of the 4 clinical criteria of IC was evaluated using liver biopsy,which was the golden standard.Results A total of 171 patients were enrolled,including 125 males and 46 females,with mean age of 45.5 ± 4.24 (22-69) year old.HAI ranged from 1 to 11 with the average value of 4.3±2.1,which was ≤ 3 in 94 cases (55.0％).Fibrosis score ranged from0 to4 with the average value of 2.0±1.6.A total of 101 (59.1 ％) cases had fibrosis score from 0 to 1.There was no significant difference in IC diagnosis rate among the 4 groups with different clinical IC diagnostic criteria.The Yourdon's index for the 4 criteria was 0.08 ～ 0.11 and the area under the curve (AUC) was 0.544 ～ 0.558,respectively,which suggested their limitation of IC diagnosis.There were only 50％ ～ 60％ patients pathologically diagnosed of IC in patients according to Chinese and APASL/AASLD guidelines.However,in the non-IC patients diagnosed with clinical criteria,there were 33.3％ ～ 51.4％ patients meeting the pathological IC diagnosis.Conclusion There were 50％ ～ 60％ patients meeting the pathological IC among HBeAg-negative CHB patients with low viral load.Among the non-IC patients diagnosed by clinical criteria,33.3％ ～ 51.4％ patients were pathologically diagnosed of IC.Based on the diagnostic golden standard of histology,clinical diagnosis of IC with current Chinese,APASL and AASLD guidelines showed low sensitivity and limited value.