目的探讨乙肝病毒(Hepatitis B Virus,HBV)感染患者血清中乙型肝炎病毒脱氧核苷酸(HBV-DNA)载量与乙肝五项指标的相关性。方法选取沛县人民医院于2022年1月—2023年1月收治的100例HBV感染患者作为研究对象,所有患者均接受HBV-DNA载量与...目的探讨乙肝病毒(Hepatitis B Virus,HBV)感染患者血清中乙型肝炎病毒脱氧核苷酸(HBV-DNA)载量与乙肝五项指标的相关性。方法选取沛县人民医院于2022年1月—2023年1月收治的100例HBV感染患者作为研究对象,所有患者均接受HBV-DNA载量与乙肝五项指标检测,并按照其HBV-DNA载量进行分组,分别为<50 IU/mL组69例、50~<10^(4) IU/mL组10例、10^(4)~10^(10) IU/mL组21例,对比3组检测结果。结果10^(4)~10^(10) IU/mL组乙型肝炎e抗体(Hepatitis B Virus e Antibody,HBeAb)、乙型肝炎e抗原(Hepatitis B e Antigen,HBeAg)、乙型肝炎表面抗原(Hapatitis B Surface Antigen,HBsAg)指标高于50~<10^(4) IU/mL组、<50 IU/mL组,50~<10^(4) IU/mL组各指标水平高于<50 IU/mL组,差异有统计学意义(P均<0.05)。相关性分析后显示,HBeAb、HBeAg、HBsAg与HBV-DNA载量呈正相关(r=0.512、0.549、0.673,P均<0.05)。结论HBV-DNA载量与HBeAb、HBeAg、HBsAg指标之间有正性关联,可为评估HBV感染程度提供一定参考依据。展开更多
目的探讨丙型肝炎病毒NS5A反式调节蛋白9(hepatitis C virus NS5Atransactivated protein 9,NS5ATP9)在乙型肝炎病毒(hepatitis B virus,HBV)共价闭合环状DNA(covalently closed circular DNA,cccDNA)形成与转录中的作用机制。方法利用...目的探讨丙型肝炎病毒NS5A反式调节蛋白9(hepatitis C virus NS5Atransactivated protein 9,NS5ATP9)在乙型肝炎病毒(hepatitis B virus,HBV)共价闭合环状DNA(covalently closed circular DNA,cccDNA)形成与转录中的作用机制。方法利用1.3拷贝HBV表达质粒转染Huh7和HepG2细胞、整合有4拷贝HBV基因组的HepG2.2.15细胞、在诱导型四环素启动子控制下表达HBV的HepAD38细胞构建NS5ATP9过表达或干扰的HBV细胞模型,收集样品和细胞上清液,提取RNA、HBV核心DNA(coreDNA)、cccDNA和蛋白,利用酶联免疫吸附试验、实时荧光定量聚合酶链反应(polymerase chain reaction,PCR)、Southern blot和Western blot技术检测HBV总RNA、前基因组RNA(pregenomic RNA,pgRNA)、乙型肝炎病毒s抗原(hepatitis B virus s antigene,HBsAg)、乙型肝炎病毒e抗原(hepatitis B virus e antigene,HBeAg)、松弛环状DNA(relax circular DNA,rcDNA)以及cccDNA水平。在HepG2细胞中转染乙型肝炎病毒x蛋白(hepatitis B virus x protein,HBx),通过免疫荧光成像及免疫共沉淀方法检测NS5ATP9与HBx的结合情况。双荧光素酶报告基因实验检测NS5ATP9对HBx启动子活性的影响。利用Huh7细胞转染HBV1.3及HBV稳定表达细胞株HepG2.2.15和HepAD38转染NS5ATP9过表达/干扰质粒,通过Western blot技术检测DDB1和SMC6的蛋白水平。结果在HBV病毒活跃的细胞中,NS5ATP9 mRNA水平[HepG2.2.15细胞:1.891±0.567比1.00±0.034,t=2.87,P=0.0351;HepAD38 tet+细胞:1.978±0.399比1.00±0.034,t=4.131,P=0.0091;HepAD38 tet-细胞:2.642±0.672比1.00±0.034,t=4.127,P=0.0091]和蛋白水平均显著增加。过表达NS5ATP9后可显著增加HBeAg[(5.402±0.327)S/COV比(2.68±0.552)S/COV,t=7.35,P=0.0018]、HBsAg[(2.846±0.185)S/COV比(1.512±0.221)S/COV,t=8.02,P=0.0013]、HBV pgRNA及rcDNA的表达水平,而干扰NS5ATP9后此增加作用消失[HBeAg:(2.029±0.09)S/COV比(3.733±0.445)S/COV,t=6.501,P=0.0029;HBsAg:(1.501±0.105)S/COV比(1.878±0.174)S/COV,t=3.216,P=0.0324)]。机制研究显示,NS5ATP9和HBx蛋白主要位于细胞核核仁内,并具有共定位信号,且NS5ATP9可显著提高HBx启动子(1071.06±79.44比488.47±40.12,t=13.09,P=0.00012)的转录活性。另外,过表达NS5ATP9可显著降低DDB1和SMC6的蛋白水平,而沉默NS5ATP9则可显著提高DDB1和SMC6的蛋白水平。结论HBV上调NS5ATP9的表达,形成HBV-NS5ATP9-HBV cccDNA-HBV的正反馈环路,NS5ATP9通过与HBx相互作用上调肝细胞中HBV cccDNA的形成与转录,进而促进慢性乙型肝炎的发生发展。展开更多
目的研究探讨乙肝孕妇大三阳和小三阳状态中乙型肝炎病毒(Hepatitis B virus,HBV)DNA载量、肝功能指标、肝纤维化标志物含量及不同HBVDNA载量孕妇的肝功能水平。方法选取临清市人民医院于2020年1月—2023年1月收治的120例乙肝孕妇作为...目的研究探讨乙肝孕妇大三阳和小三阳状态中乙型肝炎病毒(Hepatitis B virus,HBV)DNA载量、肝功能指标、肝纤维化标志物含量及不同HBVDNA载量孕妇的肝功能水平。方法选取临清市人民医院于2020年1月—2023年1月收治的120例乙肝孕妇作为研究对象,根据乙肝两对半检测结果将其分为两组,即大三阳组(n=60)和小三阳组(n=60)。比较两组HBVDNA载量、肝功能指标、肝纤维化标志物含量及不同HBVDNA载量孕妇的肝功能指标、肝纤维化标志物含量。结果大三阳组丙氨酸转移酶水平(29.00±7.62)U/L、HBVDNA水平(5.18±1.16)×10^(4)U/mL均高于小三阳组的(26.00±2.85)U/L、(2.08±1.11)×10^(4)U/mL,差异有统计学意义(t=2.856、14.956,P均<0.05)。大三阳组的重组人几丁质酶3样蛋白1水平低于小三阳组,差异有统计学意义(P<0.05)。伴随着HBVDNA载量上升,两组患者甲胎蛋白水平随之增加,但是在同等HBADNA载量下,两组甲胎蛋白水平比较,差异无统计学意义(P>0.05)。结论开展孕前抗乙肝病毒诊疗、孕期风险系数评估,采取科学有效的干预措施,均能够有效抑制乙肝在母婴中的传播。展开更多
目的分析失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与乙型肝炎病毒标志物、生化及凝血等指标的相关性。方法回顾性分析2018年1月至2020年12月我院收治的645例失代偿期乙型肝炎肝硬化患者的临床资料,根据HBV-DNA水平分为4组:阴性组、...目的分析失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与乙型肝炎病毒标志物、生化及凝血等指标的相关性。方法回顾性分析2018年1月至2020年12月我院收治的645例失代偿期乙型肝炎肝硬化患者的临床资料,根据HBV-DNA水平分为4组:阴性组、低病毒载量组(<2.0×10^(3)IU/mL)、中病毒载量组(2.0×10^(3)~2.0×10^(5)IU/mL)和高病毒载量组(>105IU/mL),测定所有患者乙型肝炎病毒血清学标志物(HBV-M)、肝功能相关生化指标(ALT、AST、TBIL、DBIL、ALB)、凝血相关指标(PT、INR、APTT、TT、D-D、PLT),比较4组患者各项指标的差异,并分析各项指标与HBV-DNA水平的相关性。结果在失代偿期乙型肝炎肝硬化患者中,HBsAg和HBeAg的定量数值随着HBV-DNA水平的升高而增高,HBsAg的明显升高主要体现在HBV-DNA阴性组和低病毒载量组之间(779.40 vs 5773.00IU/mL),而HBeAg的表达在中病毒载量组(0.19 COI)和高病毒载量组(7.96 COI)中才出现显著升高,低病毒载量组的HBeAg阳性表达率较低。随着病毒载量的升高,患者的ALT、AST、TBIL、DBIL、D/T、AFP指标均有所升高,而ALB的水平降低;除TT存在显著性差异外,PT、APTT、INR、Fib、D-D、PLT这6个指标差异均无统计学意义。经Pearson相关性分析检验,失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与ALT、AST、TBIL、DBIL、AFP、PT、APTT、TT、D-D、HBsAg、HBeAg水平呈正相关(r>0,P均<0.05),与ALB、Fib水平呈负相关(r<0,P均<0.05),与PLT、HBeAb水平不存在相关性。结论在失代偿期乙型肝炎肝硬化患者中,血清HBV-DNA载量与HBsAg、HBeAg表达水平密切相关,与ALT、AST、TBIL、DBIL、D/T、ALB等肝功能相关生化指标相关,与凝血相关指标存在关联,但在不同HBV-DNA载量组中无差异。HBV-DNA载量可作为HBeAg阴性患者肝脏损害程度的有效预测指标。展开更多
BACKGROUND Chronic hepatitis B virus(HBV)infection remains a major global public health problem.Chronic hepatitis B(CHB)patients can be divided into treatment indication and non-treatment indication individuals accord...BACKGROUND Chronic hepatitis B virus(HBV)infection remains a major global public health problem.Chronic hepatitis B(CHB)patients can be divided into treatment indication and non-treatment indication individuals according to alanine transaminase(ALT),HBV DNA,serum hepatitis B e antigen status,disease status[liver cirrhosis,hepatocellular carcinoma(HCC),or liver failure],liver necroinflammation or fibrosis,patients’age,and family history of HCC or cirrhosis.For example,normal ALT patients in‘immune-tolerant’phase with HBV DNA higher than 10^(7)or 2×10^(7)IU/mL,and those in‘inactive-carrier’phase with HBV DNA lower than 2×10^(3)IU/mL do not require antiviral therapy.However,is it reasonable to set the defined values of HBV DNA as the fundamental basis to estimate the disease state and to determine whether to start treatment?In fact,we should pay more attention to those who do not match the treatment indications(grayzone patients both in the indeterminate phase and in the‘inactive-carrier’phase).AIM To analyze the correlation of HBV DNA level and liver histopathological severity,and to explore the significance of HBV DNA for CHB with normal ALT.METHODS From January 2017 to December 2021,a retrospective cross-sectional set of 1299 patients with chronic HBV infection(HBV DNA>30 IU/mL)who underwent liver biopsy from four hospitals,including 634 with ALT less than 40 U/L.None of the patients had received anti-HBV treatment.The degrees of liver necroinflammatory activity and liver fibrosis were evaluated according to the Metavir system.On the basis of the HBV DNA level,patients were divided into two groups:Low/moderate replication group,HBV DNA≤10^(7)IU/mL[7.00 Log IU/mL,the European Association for the Study of the Liver(EASL)guidelines]or≤2×10^(7)IU/mL[7.30 Log IU/mL,the Chinese Medical Association(CMA)guidelines];high replication group,HBV DNA>10^(7)IU/mL or>2×10^(7)IU/mL.Relevant factors(demographic characteristics,laboratory parameters and noninvasive models)for liver histopathological severity were analyzed by univariate analysis,logistics analysis and propensity score-matched analysis.RESULTS At entry,there were 21.45%,24.29%,and 30.28%of the patients had liver histopathological severities with≥A2,≥F2,and≥A2 or/and≥F2,respectively.HBV DNA level(negative correlation)and noninvasive model liver fibrosis 5 value(positive correlation)were independent risk factors for liver histopathological severities(liver necroinflammation,liver fibrosis,and treatment indication).The AUROCs of the prediction probabilities(PRE_)of the models mentioned above(<A2 vs≥A2,<F2 vs≥F2,<A2 and<F2 vs≥A2 or/and≥F2)were 0.814(95%CI:0.770-0.859),0.824(95%CI:0.785-0.863),and 0.799(95%CI:0.760-0.838),respectively.HBV DNA level(negative correlation)was still an independent risk factor when diagnostic models were excluded,the P values(<A2 vs≥A2,<F2 vs≥F2,<A2 and<F2 vs≥A2 or/and≥F2)were 0.011,0.000,and 0.000,respectively.For the propensity score-matched pairs,whether based on EASL guidelines or CMA guidelines,the group with significant liver histology damage(≥A2 or/and≥F2)showed much lower HBV DNA level than the group with non-significant liver histology damage(<A2 and<F2).Patients in the moderate replication group(with indeterminate phase)had the most serious liver disease pathologically and hematologically,followed by patients in the low replication group(with‘inactive-carrier’phase)and then the high replication group(with‘immune-tolerant’phase).CONCLUSION HBV DNA level is a negative risk factor for liver disease progression.The phase definition of CHB may be revised by whether the level of HBV DNA exceeds the detection low limit value.Patients who are in the indeterminate phase or‘inactive carriers’should receive antiviral therapy.展开更多
文摘目的探讨乙肝病毒(Hepatitis B Virus,HBV)感染患者血清中乙型肝炎病毒脱氧核苷酸(HBV-DNA)载量与乙肝五项指标的相关性。方法选取沛县人民医院于2022年1月—2023年1月收治的100例HBV感染患者作为研究对象,所有患者均接受HBV-DNA载量与乙肝五项指标检测,并按照其HBV-DNA载量进行分组,分别为<50 IU/mL组69例、50~<10^(4) IU/mL组10例、10^(4)~10^(10) IU/mL组21例,对比3组检测结果。结果10^(4)~10^(10) IU/mL组乙型肝炎e抗体(Hepatitis B Virus e Antibody,HBeAb)、乙型肝炎e抗原(Hepatitis B e Antigen,HBeAg)、乙型肝炎表面抗原(Hapatitis B Surface Antigen,HBsAg)指标高于50~<10^(4) IU/mL组、<50 IU/mL组,50~<10^(4) IU/mL组各指标水平高于<50 IU/mL组,差异有统计学意义(P均<0.05)。相关性分析后显示,HBeAb、HBeAg、HBsAg与HBV-DNA载量呈正相关(r=0.512、0.549、0.673,P均<0.05)。结论HBV-DNA载量与HBeAb、HBeAg、HBsAg指标之间有正性关联,可为评估HBV感染程度提供一定参考依据。
文摘目的探讨丙型肝炎病毒NS5A反式调节蛋白9(hepatitis C virus NS5Atransactivated protein 9,NS5ATP9)在乙型肝炎病毒(hepatitis B virus,HBV)共价闭合环状DNA(covalently closed circular DNA,cccDNA)形成与转录中的作用机制。方法利用1.3拷贝HBV表达质粒转染Huh7和HepG2细胞、整合有4拷贝HBV基因组的HepG2.2.15细胞、在诱导型四环素启动子控制下表达HBV的HepAD38细胞构建NS5ATP9过表达或干扰的HBV细胞模型,收集样品和细胞上清液,提取RNA、HBV核心DNA(coreDNA)、cccDNA和蛋白,利用酶联免疫吸附试验、实时荧光定量聚合酶链反应(polymerase chain reaction,PCR)、Southern blot和Western blot技术检测HBV总RNA、前基因组RNA(pregenomic RNA,pgRNA)、乙型肝炎病毒s抗原(hepatitis B virus s antigene,HBsAg)、乙型肝炎病毒e抗原(hepatitis B virus e antigene,HBeAg)、松弛环状DNA(relax circular DNA,rcDNA)以及cccDNA水平。在HepG2细胞中转染乙型肝炎病毒x蛋白(hepatitis B virus x protein,HBx),通过免疫荧光成像及免疫共沉淀方法检测NS5ATP9与HBx的结合情况。双荧光素酶报告基因实验检测NS5ATP9对HBx启动子活性的影响。利用Huh7细胞转染HBV1.3及HBV稳定表达细胞株HepG2.2.15和HepAD38转染NS5ATP9过表达/干扰质粒,通过Western blot技术检测DDB1和SMC6的蛋白水平。结果在HBV病毒活跃的细胞中,NS5ATP9 mRNA水平[HepG2.2.15细胞:1.891±0.567比1.00±0.034,t=2.87,P=0.0351;HepAD38 tet+细胞:1.978±0.399比1.00±0.034,t=4.131,P=0.0091;HepAD38 tet-细胞:2.642±0.672比1.00±0.034,t=4.127,P=0.0091]和蛋白水平均显著增加。过表达NS5ATP9后可显著增加HBeAg[(5.402±0.327)S/COV比(2.68±0.552)S/COV,t=7.35,P=0.0018]、HBsAg[(2.846±0.185)S/COV比(1.512±0.221)S/COV,t=8.02,P=0.0013]、HBV pgRNA及rcDNA的表达水平,而干扰NS5ATP9后此增加作用消失[HBeAg:(2.029±0.09)S/COV比(3.733±0.445)S/COV,t=6.501,P=0.0029;HBsAg:(1.501±0.105)S/COV比(1.878±0.174)S/COV,t=3.216,P=0.0324)]。机制研究显示,NS5ATP9和HBx蛋白主要位于细胞核核仁内,并具有共定位信号,且NS5ATP9可显著提高HBx启动子(1071.06±79.44比488.47±40.12,t=13.09,P=0.00012)的转录活性。另外,过表达NS5ATP9可显著降低DDB1和SMC6的蛋白水平,而沉默NS5ATP9则可显著提高DDB1和SMC6的蛋白水平。结论HBV上调NS5ATP9的表达,形成HBV-NS5ATP9-HBV cccDNA-HBV的正反馈环路,NS5ATP9通过与HBx相互作用上调肝细胞中HBV cccDNA的形成与转录,进而促进慢性乙型肝炎的发生发展。
文摘目的研究探讨乙肝孕妇大三阳和小三阳状态中乙型肝炎病毒(Hepatitis B virus,HBV)DNA载量、肝功能指标、肝纤维化标志物含量及不同HBVDNA载量孕妇的肝功能水平。方法选取临清市人民医院于2020年1月—2023年1月收治的120例乙肝孕妇作为研究对象,根据乙肝两对半检测结果将其分为两组,即大三阳组(n=60)和小三阳组(n=60)。比较两组HBVDNA载量、肝功能指标、肝纤维化标志物含量及不同HBVDNA载量孕妇的肝功能指标、肝纤维化标志物含量。结果大三阳组丙氨酸转移酶水平(29.00±7.62)U/L、HBVDNA水平(5.18±1.16)×10^(4)U/mL均高于小三阳组的(26.00±2.85)U/L、(2.08±1.11)×10^(4)U/mL,差异有统计学意义(t=2.856、14.956,P均<0.05)。大三阳组的重组人几丁质酶3样蛋白1水平低于小三阳组,差异有统计学意义(P<0.05)。伴随着HBVDNA载量上升,两组患者甲胎蛋白水平随之增加,但是在同等HBADNA载量下,两组甲胎蛋白水平比较,差异无统计学意义(P>0.05)。结论开展孕前抗乙肝病毒诊疗、孕期风险系数评估,采取科学有效的干预措施,均能够有效抑制乙肝在母婴中的传播。
文摘目的分析失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与乙型肝炎病毒标志物、生化及凝血等指标的相关性。方法回顾性分析2018年1月至2020年12月我院收治的645例失代偿期乙型肝炎肝硬化患者的临床资料,根据HBV-DNA水平分为4组:阴性组、低病毒载量组(<2.0×10^(3)IU/mL)、中病毒载量组(2.0×10^(3)~2.0×10^(5)IU/mL)和高病毒载量组(>105IU/mL),测定所有患者乙型肝炎病毒血清学标志物(HBV-M)、肝功能相关生化指标(ALT、AST、TBIL、DBIL、ALB)、凝血相关指标(PT、INR、APTT、TT、D-D、PLT),比较4组患者各项指标的差异,并分析各项指标与HBV-DNA水平的相关性。结果在失代偿期乙型肝炎肝硬化患者中,HBsAg和HBeAg的定量数值随着HBV-DNA水平的升高而增高,HBsAg的明显升高主要体现在HBV-DNA阴性组和低病毒载量组之间(779.40 vs 5773.00IU/mL),而HBeAg的表达在中病毒载量组(0.19 COI)和高病毒载量组(7.96 COI)中才出现显著升高,低病毒载量组的HBeAg阳性表达率较低。随着病毒载量的升高,患者的ALT、AST、TBIL、DBIL、D/T、AFP指标均有所升高,而ALB的水平降低;除TT存在显著性差异外,PT、APTT、INR、Fib、D-D、PLT这6个指标差异均无统计学意义。经Pearson相关性分析检验,失代偿期乙型肝炎肝硬化患者血清HBV-DNA水平与ALT、AST、TBIL、DBIL、AFP、PT、APTT、TT、D-D、HBsAg、HBeAg水平呈正相关(r>0,P均<0.05),与ALB、Fib水平呈负相关(r<0,P均<0.05),与PLT、HBeAb水平不存在相关性。结论在失代偿期乙型肝炎肝硬化患者中,血清HBV-DNA载量与HBsAg、HBeAg表达水平密切相关,与ALT、AST、TBIL、DBIL、D/T、ALB等肝功能相关生化指标相关,与凝血相关指标存在关联,但在不同HBV-DNA载量组中无差异。HBV-DNA载量可作为HBeAg阴性患者肝脏损害程度的有效预测指标。
基金Supported by Zhejiang Provincial Basic and Public Welfare Foundation,No.LGF22H030002Ningbo Science and Technology Program,No.2021S182+1 种基金Major Medical Scientific Research Foundation of National Health Commission of the People's Republic of China-Zhejiang Province,No.WKJ-ZJ-2341Zhejiang Province and Ningbo City Coconstructed Project of Leading Medical&Health Discipline,No.2016-S04.
文摘BACKGROUND Chronic hepatitis B virus(HBV)infection remains a major global public health problem.Chronic hepatitis B(CHB)patients can be divided into treatment indication and non-treatment indication individuals according to alanine transaminase(ALT),HBV DNA,serum hepatitis B e antigen status,disease status[liver cirrhosis,hepatocellular carcinoma(HCC),or liver failure],liver necroinflammation or fibrosis,patients’age,and family history of HCC or cirrhosis.For example,normal ALT patients in‘immune-tolerant’phase with HBV DNA higher than 10^(7)or 2×10^(7)IU/mL,and those in‘inactive-carrier’phase with HBV DNA lower than 2×10^(3)IU/mL do not require antiviral therapy.However,is it reasonable to set the defined values of HBV DNA as the fundamental basis to estimate the disease state and to determine whether to start treatment?In fact,we should pay more attention to those who do not match the treatment indications(grayzone patients both in the indeterminate phase and in the‘inactive-carrier’phase).AIM To analyze the correlation of HBV DNA level and liver histopathological severity,and to explore the significance of HBV DNA for CHB with normal ALT.METHODS From January 2017 to December 2021,a retrospective cross-sectional set of 1299 patients with chronic HBV infection(HBV DNA>30 IU/mL)who underwent liver biopsy from four hospitals,including 634 with ALT less than 40 U/L.None of the patients had received anti-HBV treatment.The degrees of liver necroinflammatory activity and liver fibrosis were evaluated according to the Metavir system.On the basis of the HBV DNA level,patients were divided into two groups:Low/moderate replication group,HBV DNA≤10^(7)IU/mL[7.00 Log IU/mL,the European Association for the Study of the Liver(EASL)guidelines]or≤2×10^(7)IU/mL[7.30 Log IU/mL,the Chinese Medical Association(CMA)guidelines];high replication group,HBV DNA>10^(7)IU/mL or>2×10^(7)IU/mL.Relevant factors(demographic characteristics,laboratory parameters and noninvasive models)for liver histopathological severity were analyzed by univariate analysis,logistics analysis and propensity score-matched analysis.RESULTS At entry,there were 21.45%,24.29%,and 30.28%of the patients had liver histopathological severities with≥A2,≥F2,and≥A2 or/and≥F2,respectively.HBV DNA level(negative correlation)and noninvasive model liver fibrosis 5 value(positive correlation)were independent risk factors for liver histopathological severities(liver necroinflammation,liver fibrosis,and treatment indication).The AUROCs of the prediction probabilities(PRE_)of the models mentioned above(<A2 vs≥A2,<F2 vs≥F2,<A2 and<F2 vs≥A2 or/and≥F2)were 0.814(95%CI:0.770-0.859),0.824(95%CI:0.785-0.863),and 0.799(95%CI:0.760-0.838),respectively.HBV DNA level(negative correlation)was still an independent risk factor when diagnostic models were excluded,the P values(<A2 vs≥A2,<F2 vs≥F2,<A2 and<F2 vs≥A2 or/and≥F2)were 0.011,0.000,and 0.000,respectively.For the propensity score-matched pairs,whether based on EASL guidelines or CMA guidelines,the group with significant liver histology damage(≥A2 or/and≥F2)showed much lower HBV DNA level than the group with non-significant liver histology damage(<A2 and<F2).Patients in the moderate replication group(with indeterminate phase)had the most serious liver disease pathologically and hematologically,followed by patients in the low replication group(with‘inactive-carrier’phase)and then the high replication group(with‘immune-tolerant’phase).CONCLUSION HBV DNA level is a negative risk factor for liver disease progression.The phase definition of CHB may be revised by whether the level of HBV DNA exceeds the detection low limit value.Patients who are in the indeterminate phase or‘inactive carriers’should receive antiviral therapy.
