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[乙肝肝硬化患者长期核苷(酸)类似物抗病毒治疗后HBV DNA低于HBV RNA检测下限的分析及意义]

[Analysis and significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term NAs antiviral therapy in patients with hepatitis B virus cirrhosis].

作者信息

Wang C Y, Cao Y, Feng Y M, Li J, Jiang B, Zhang Y, Wen J, Zhu Y J, Li J

机构信息

Department of Chronic Liver Disease,Tianjin Second People's Hospital, Tianjin 300192, China.

Hepatopathy Research Institute, Tianjin Second People's Hospital, Tianjin 300192, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2022 Jul 20;30(7):758-762. doi: 10.3760/cma.j.cn501113-20201126-00629.

Abstract

To analyze the significance of HBV DNA below the lower detection limit of HBV RNA levels after long-term nucleos(t)ide analogues (NAs) antiviral therapy in patients with hepatitis B virus cirrhosis. 97 cases with hepatitis B virus cirrhosis treated with NAs antiviral therapy for at least 3 years between May 2018 to July 2019 were selected. High-sensitivity HBV DNA (<20 IU/ml), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), HBsAg, HBeAg and HBV RNA at least twice every 6 months were detected. According to Child-Pugh classification, HBeAg, HBsAg level, and HBV RNA level intergroup comparison was performed. Rank sum test, test and linear regression analysis were performed on the data. Compared with the HBV RNA level of child-Pugh class A patients, the HBV RNA level of Child-Pugh class B+C patients were significantly higher [4.1 (0,4.9) log copies/ml and 2.0 (0,3.5) log copies/ml], and the difference was statistically significant (=2.370, <0.05). According to different HBeAg levels, they were divided into HBeAg positive and negative group, and the quantitative comparison of HBV RNA levels between the two groups were 2.0 (0, 4.5) log copies/ml and 1.0 (1.0, 2.0) log copies/ml, respectively, and the difference was statistically significant (=3.233, <0.05). According to different HBsAg levels, they were divided into three groups: HBsAg≤100 IU/ml, 100<HBsAg<1 000 IU/ml, and HBsAg≥1 000 IU/ml, and the quantitative comparison of HBV RNA levels among the three groups were 0 (0, 2.0) log, 2.0 (0,4.6) log and 2.2 (2.0, 4.7) log copies/ml, respectively, and the difference was statistically significant (=11.265, <0.05). Gender, age, ALT, AST, GGT, HBsAg, and HBeAg were included for linear regression analysis, and the HBsAg and AST levels were correlated with HBV RNA quantification (<0.05). Adverse events occurrence during 1-year follow-up were recorded. 19 (31.7%) out of 60 cases had adverse events with detectable HBV RNA, and 3 (8.1%) out of 37 cases had adverse events with undetectable HBV RNA, and the difference was statistically significant (=7.24, <0.05). HBV RNA can still be detected after HBV DNA falls below the detection limit in patients with hepatitis B virus cirrhosis treated with long-term NAs antiviral therapy. HBV RNA quantification level is higher in patients with Child Pugh class B and C. Patients with detectable HBV RNA has higher proportion of adverse events, and AST and HBsAg levels may be correlated with serum HBV RNA.

摘要

分析长期核苷(酸)类似物(NAs)抗病毒治疗后乙肝病毒肝硬化患者中低于HBV RNA水平检测下限的HBV DNA的意义。选取2018年5月至2019年7月间接受NAs抗病毒治疗至少3年的97例乙肝病毒肝硬化患者。每6个月至少检测两次高灵敏度HBV DNA(<20 IU/ml)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转移酶(GGT)、HBsAg、HBeAg和HBV RNA。根据Child-Pugh分级进行组间HBeAg、HBsAg水平及HBV RNA水平比较。对数据进行秩和检验、检验及线性回归分析。与Child-Pugh A级患者的HBV RNA水平相比,Child-Pugh B + C级患者的HBV RNA水平显著更高[4.1(0,4.9)log拷贝/ml和2.0(0,3.5)log拷贝/ml],差异有统计学意义(=2.370,<0.05)。根据不同HBeAg水平分为HBeAg阳性组和阴性组,两组HBV RNA水平定量比较分别为2.0(0,4.5)log拷贝/ml和1.0(1.0,2.0)log拷贝/ml,差异有统计学意义(=3.233,<0.05)。根据不同HBsAg水平分为三组:HBsAg≤100 IU/ml、100<HBsAg<1000 IU/ml、HBsAg≥1000 IU/ml,三组HBV RNA水平定量比较分别为0(0,2.0)log、2.0(0,4.6)log和2.2(2.0,4.7)log拷贝/ml,差异有统计学意义(=11.265,<0.05)。纳入性别、年龄、ALT、AST、GGT、HBsAg和HBeAg进行线性回归分析,HBsAg和AST水平与HBV RNA定量相关(<0.05)。记录1年随访期间不良事件发生情况。60例可检测到HBV RNA的患者中有19例(31.7%)发生不良事件,37例未检测到HBV RNA的患者中有3例(8.1%)发生不良事件,差异有统计学意义(=7.24,<0.05)。长期接受NAs抗病毒治疗的乙肝病毒肝硬化患者HBV DNA降至检测下限后仍可检测到HBV RNA。Child Pugh B级和C级患者的HBV RNA定量水平更高。可检测到HBV RNA的患者不良事件比例更高,且AST和HBsAg水平可能与血清HBV RNA相关。

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