[Analysis of liver pathological characteristics and exploration of noninvasive markers of liver fibrosis in children with chronic hepatitis B].

Objective: To analyze and summarize the characteristics of liver pathology and their relation to clinical markers and further explore noninvasive markers of liver fibrosis in children with chronic hepatitis B. Methods: Data of 80 hospitalized children with chronic hepatitis B who underwent liver biopsy without antiviral treatment from 2011 to 2020 were retrospectively analyzed. Inflammation and liver fibrosis characteristics were analyzed in children of different ages and genders. Variables with good correlation with liver fibrosis stage were selected to establish a non-invasive diagnostic score of liver fibrosis in children. Measurement data was used to compare the t-test or rank sum test. Mantel-Haenszel χ (2) test was used for bidirectional ordered grouping data. Spearman's rank correlation test was used for rank correlation analysis. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of the newly established diagnostic score in children with liver fibrosis. Results: The median age of the children was 6.4 years. HBV DNA level was high (P50 = 7.6 log(10) IU/ml), and serum alanine aminotransferase (ALT) in P50 was 171 U/L (< ULN: 5 cases, ULN-2ULN: 10 cases, > 2 ULN: 65 cases). Pathological analysis showed that the incidence of liver tissue inflammation was 97.5%, and the proportion of patients with G≥2 was 42.5%, while S≥2 was 36.3%. The incidence rate of liver fibrosis and liver cirrhosis was 81.3%, and 1.3%, respectively. The changes in liver tissue inflammation and fibrosis were gradually aggravated with the increase of age, and the proportion of high-grade inflammation and liver fibrosis in male children was higher than that in female children. Serum levels of glutamyl transpeptidase (GGT), γ-glutamyltransferase/platelet ratio (GPR) and HBeAg had a good correlation with fibrosis stage (r(s) = 0.397, 0.389, and - 0.311) in children with chronic hepatitis B. The combination of GGT, GPR and HBeAg can establish a non-invasive diagnostic score for evaluating liver fibrosis in children. When the score is less than 1.5, it can be diagnosed as S0, and 1.5 ≤ score < 3.5, it can be diagnosed as S1; 3.5 ≤ score < 5.5, the diagnosis of fibrosis is S2; score≥ 5.5, the diagnosis of fibrosis is S≥3. The sensitivity and specificity were 80%, 83%, 86%, and 53%, 55%, 67%, respectively. Conclusion: The incidence of liver tissue inflammation in children with chronic hepatitis B with elevated and fluctuating transaminase levels is high, and the pathological changes of liver tissue aggravate with the age of the children. GGT, GPR and HBeAg have a good correlation with liver fibrosis in children with chronic hepatitis B. Therefore, combining the above-mentioned markers to establish a new noninvasive diagnostic score has certain diagnostic value for liver fibrosis stage S0-S3 in children with chronic hepatitis B.目的： 分析总结儿童乙型肝炎患者肝脏病理学特征及其与临床指标间的相关性，进一步探索可用于儿童肝脏纤维化评估的非侵入性指标。 方法： 回顾性分析2011年至2020年住院的80例行肝活检的未经抗病毒治疗的乙型肝炎患儿资料。分析不同年龄段及不同性别患儿的炎症和纤维化特征，选取与肝纤维化分期相关性较好的变量建立儿童肝纤维化非侵入性诊断评分。采用t检验或秩和检验比较计量资料，双向有序分组资料采用Mantel-Haenszel χ(2)检验，等级相关性分析采用Spearman秩相关性检验，采用受试者操作特征曲线(ROC)评估新建立诊断评分对儿童肝纤维化的诊断价值。 结果： 患儿中位年龄为6.4岁；HBV DNA水平较高(P50 = 7.6 log(10) IU/ml）;血清丙氨酸转氨酶（ALT）P50 = 171 U/L [<正常值上限（ULN）：5例；1~2 ULN：10例；> 2 ULN：65例]。病理学分析显示肝组织炎症的发生率为97.5%，G≥2者占比为42.5%；S≥2者占比为36.3%，肝纤维化的发生率为81.3%，肝硬化发生率为1.3%。肝组织炎症和纤维化改变随着患儿年龄增加逐渐加重，且男性患儿高等级炎症及纤维化改变的比例高于女性患儿。慢性乙型肝炎儿童的血清γ-谷氨酰转移酶（GGT）水平、γ-谷氨酰转移酶/血小板比值（GPR）及HBeAg水平与纤维化分期具有较好相关性（r(s)分别为0.397、0.389、-0.311），将GGT、GPR及HBeAg联合，可建立评估儿童患者肝纤维化的非侵入性诊断评分，当评分< 1.5时，可诊断纤维化S0，1.5≤评分< 3.5时，可诊断纤维化S1；3.5≤评分< 5.5时，诊断纤维化S2；评分≥5.5时，诊断纤维化S≥3。其敏感度分别为80%、83%、86%，特异度分别为53%、55%、67%。 结论： 转氨酶升高波动的慢性乙型肝炎患儿肝组织炎症发生率高，且肝组织病理改变随着患儿年龄增长而加重。GGT、GPR及HBeAg与乙型肝炎患儿肝脏纤维化相关性好，联合上述指标建立新的非侵入性诊断评分对慢性乙型肝炎儿童S0~S3期纤维化有一定诊断价值。.