HBeAg阴性低病毒载量慢性乙型肝炎患者的肝组织学状态与转归  

Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load

作　　者：邓德丽 江建宁[1] 苏明华[1] 王荣明[1] 臧伟伟 零小樟 韦慧兰 梁先帅 周珲堃 何文明 郭荣晟 Deng Deli;Jiang Jianning;Su Minghua;Wang Rongming;Zang Weiwei;Ling Xiaozhatig;Wei Huilan;Liang Xianshuai;Zhou Huikun;He Wenming;Guo Rongsheng(Department of Infectious Diseases,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院感染性疾病科,南宁530021

出　　处：《中华肝脏病杂志》2020年第12期1013-1017,共5页Chinese Journal of Hepatology

基　　金：国家自然科学基金项目(81960115):“十三五”国家科技重大专项(2017ZX10202201);广西病毒性肝炎防治研究重点实验室开放课题基金项目(GXCDCKL201802、GXCDCKL202001);区域性高发肿瘤早期防治研究教育部重点实验室自主课题(GKE2018-05、GKE2019-04);广西医科大学青年科学基金项目(GXMUYSF201910)。

摘　　要：目的回顾性分析HBeAg阴性的HBV DNA低病毒载量慢性乙型肝炎(CHB)患者的血清学、病毒学、生物化学及肝组织学状态及其临床转归,探讨HBeAg阴性低病毒载量的CHB患者抗病毒治疗的必要性。方法从慢性:HBV感染者随访队列中纳入HBV DNA水平<4lg拷贝/ml,并做肝活组织病理检查的99例HBeAg阴性的CHB患者,其中23例做了第二次肝活组织病理检查。分析患者肝组织炎症、纤维化程度及肝细胞HBSAg和HBcAg状态与年龄、性别、家族史,HBV DNA载量、血清学标志物等指标的关系。比较两次肝活组织病理检查病理肝组织学差异。分析核苷(酸)类似物(NAs)治疗对患者转归的影响。多因素分析采用二分类logistic回归模型,Log-Rank检验比较未NAs治疗患者与NAs治疗患者的肝细胞癌(HCC)累计发生率。结果基线肝组织学状况:58.6%(58/99)患者肝组织病理达到明显肝组织损伤(G≥2和/或S≥2)﹔单因素logistic回归分析显示肝硬化(LC)家族史、HBsAg阳性家族史、丙氨酸转氨酶、天冬氨酸转氨酶四个因素与明显肝组织损伤呈正相关,多因素logistic回归显示的LC家族史是患者明显肝组织损伤(G≥2和/或S≥2)的主要危险因素。23例患者间隔4.5年行第二次肝活组织病理检查,其中10例未治疗的患者第二次肝活组织病理检查肝组织学有进展,明显肝组织损伤从50.0%上升到90.0%,另13例NAs治疗后第二次肝活组织病理检查肝组织学有改善,明显肝组织损伤从61.5%下降到46.2%。未抗病毒治疗患者5年HCC累计发生率显著高于NAs治疗患者(17.7%对比3.8%,P=0.046)。结论HBeAg阴性低病毒载量的CHB患者,大多数肝活组织病理检查达到抗病毒指征,尤其是有LC家族史的患者,不抗病毒治疗肝组织损伤进行性加重、HCC发生率高﹔建议HBeAg阴性低病毒载量的CHB患者,尤其是年龄大于30岁、有LC或HCC家族史的患者,无论丙氨酸转氨酶水平如何,应该及早启动抗病毒�Objective To retrospectively analyze the serological,virological,biochemical,liver histological status and clinical outcomes in HBcAg-negative chronic hepatitis B(CHB)patients with low HBV viral load,and to explore the necessity of antiviral therapy for these paticnts.Methods A total of 99 HBeAg-negative CHB patients with HBV DNA level<4 lg copies/ml who performed liver biopsy at the bascline were enrolled from the follow-up cohort.Among them,23 cases received the second liver biopsy during follow-up.The relationships among the degree of infammation and fibrosis of liver tissues,the status of HBsAg and HBcAg,agc,gender,family history,HBV DNA load,serological markers and other indicators were analyzed.The pathological differences between two liver biopsy examinations were compared.The effect of nucleos(t)ide analogues(NAs)treatment on patient's clinical outcomes were analyzed.For multivariate analysis,a binary logistic regression model was performed.Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma(HCC)in NAs-treated and non-NA streated patients.Results Baseline liver histology status showed that 58.6%(58/99)patients had obvious liver tissue damage in their baseline liver tissue pathology(G≥2 and or S≥2).Univariate logistic regression analysis showed that a liver cihosis(LC)family history,a HBsAg-positive family history,baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage.Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage.Twenty-three cases had received a second liver biopsy after an interval of 4.5 years.In 10 untreated cases,the second liver biopsy results showed the rate of obvious liver tissue damage(G≥2 and or S≥2)increased from 50.0%to 90.0%.In the other 13 cases who received NAs treatment,the second liver biopsy showed improvement in liver histology,and the rate of obvious liver tissue damage decreased from 61.5% to

关 键 词：肝炎 乙型 慢性 肝细胞癌 核苷(酸)类似物 肝组织炎症活动度 肝组织纤维化 

分 类 号：R512.62[医药卫生—内科学]