肝功能正常的慢性乙型肝炎病毒感染者血清HBeAg及HBV DNA与肝组织病理改变的关系

目的了解肝功能正常的慢性乙型肝炎病毒（HBV）感染者肝组织病理改变特征,并分析血清HBeAg及HBV DNA定量与肝组织病理改变的关系。方法选取肝功能正常的慢性HBV感染者90例,行肝穿刺病理检查,依据血清HBeAg及HBV DNA将患者分组,分别比较HBeAg阳性和阴性组及HBV DNA阳性和阴性组患者肝组织炎症分级和纤维化分期结果。结果90例患者100%存在肝组织损伤,其中肝硬化8例（8.9%）;慢性乙型肝炎轻度62例（68.9%）,中度8例（8.9%）,重度12例（13.3%）。82例病理诊断慢性乙型肝炎的患者中,炎症分级G≥2者30例（36.6%）;纤维化分期S≥2者28例（34.15%）。HBeAg阴性组病理炎症分级及纤维化分期均明显重于阳性组（P值均〈0.05）。HBV DNA阴性和阳性组肝组织炎症分级和纤维化分期差异均无统计学意义。结论肝功能正常的慢性HBV感染者,肝组织病理皆非＂正常＂;血清HBeAg、HBV DNA均不能反映肝脏损伤情况;对此类患者制定治疗方案时应考虑肝组织病理检查结果。     

慢性乙型肝炎患者血清HBeAg、HBV DNA与肝组织炎症关系的探讨

目的探讨慢性乙型肝炎血清HBeAg及HBV DNA水平和肝组织炎症损害的关系.方法采用微粒子免疫捕捉分析法和荧光定量聚合酶链反应分别对74例HBeAg阴性和73例HBeAg阳性慢性乙型肝炎患者进行血清HBeAg、HBV DNA定量检测和肝组织活检病理炎症分级,对比分析结果.结果74例HBeAg阴性慢性乙型肝炎患者中27例（36%）血清HBV DNA＞105拷贝/ml,随着G1～G4肝组织炎症损害级别的增高其所占例数也相应增高,统计学分析HBV DNA水平与肝组织炎症病理分级的相关性有显著意义;血清HBeAg定量0～29 PEIU/ml,随肝组织炎症病理分级上升定量阳性（＞0.28 PEIU/ml）的病例比率增加,经统计学分析两者具有相关性.73例HBeAg阳性慢性乙型肝炎患者中有49例（67%）血清HBV DNA＞105拷贝/ml,血清HBeAg及HBV DNA水平与肝组织炎症分级无相关性.结论血清HBV DNA水平可作为判断HBeAg阴性慢性乙型肝炎患者肝组织炎症损害程度的指标,血清HBV DNA水平愈高肝组织炎症损害往往愈重.36%的HBeAg阴性慢性乙型肝炎患者血清HBeAg水平低下而HBV DNA复制活跃,可能存在HBV的前C区终止突变合并C区突变.血清HBV DNA水平不能反映HBeAg阳性慢性乙型肝炎肝组织炎症损害的程度.     

172例慢性乙型肝炎患者肝脏病理与血清HBV DNA水平的关系

目的:探讨慢性乙型肝炎(CHB)肝脏病理与血清HBV DNA水平的关系.方法:172例慢性乙型肝炎患者根据血清免疫学指标分为HBeAg阳性组和HBeAg阴性组,均进行肝穿刺组织学检查及采用实时荧光定量PCR法检测HBV DNA.结果:不论HBeAg阳性还是HBeAg阴性CHB患者炎症分级从G0到G4分为5级,结果显示各级患者HBV DNA含量比较差异无显著性意义(P＞0.05).CHB患者纤维化分期从S0到S4分为5期,结果显示各期之间HBV DNA含量比较差异无显著性意义(P＞0.05).结论:不论HBeAg阳性还是HBeAg阴性CHB患者,肝脏病理分级分期与血清HBV DNA水平无明显相关性.     

前S1蛋白与病毒DNA和核心抗原对乙型肝炎病毒复制诊断的对比

目的 分析前S1(Pre-S1)蛋白在诊断慢性乙型病毒性肝炎病毒复制中的作用。 方法 收集慢性乙型病毒性肝炎患者共104例,均经肝活组织检查证实。检测其Pre S1蛋白,HBV标志物与HBV DNA。结果 HBsAg、HBeAg、抗-HBc阳性者29例,HBV DNA与Pre-S1蛋白的检出率均达96.5％,这组患者存在病毒的高复制。HBsAg、抗-HBe和抗-HBc阳性者65例,HBV DNA与Pre-S1蛋白的检出率分别为81.5％和72.3％;HBsAg和抗-HBc阳性者8例,HBV DNA与Pre-S1蛋白的检出率分别为87.5％、75.0％,说明部分HBeAg阴性而抗-HBe阳性/阴性的患者仍存在着病毒复制。以HBV DNA定量>103拷贝/ml为诊断标准,HBV DNA阳性患者HBeAg、Pre-S1蛋白的检出率分别为31.5％(28/89)、80.9％(72/89);两者与HBV DNA的总符合率分别为40.0％(42/104)、82.0％(85/104)。HBV DNA与HBeAg检出率差异有显著性(x2=53.397,P<0.001);HBV DNA与Pre-S1蛋白检出率差异无显著性。 结论Pre-S1蛋白较HBeAg更敏感的反映了HBV复制的情况。     

乙型肝炎病毒前C区变异与慢性乙型肝炎病理改变的相关性

目的 探讨慢性乙型肝炎中乙型肝炎病毒（HBV）前C区1896突变与肝组织病理的关系。方法 对173例慢性乙型肝炎患者进行肝活检,观察肝组织病理分级（G）和分期（S）情况,同时检测乙型肝炎病毒的e系统状态和HBV前c区1896阳性患者（20％）;随着肝组织炎症活动度和纤维化程度的进展,变异株检出率似乎有增加趋势,但无统计学意义（P＝0．98和P=0．052)。结论 HBV前C区变异在HBeAg阴性组高于HBeAg阳性组;未发现HBV前C1896变异与慢性乙型肝炎的炎症分级和纤维化分期有相关关系。     

血清HBsAg、HBcrAg和HBV DNA预测慢性乙型肝炎肝组织病理状态的性能评价

目的评价血清HBsAg、HBcrAg、HBV DNA预测慢性乙型肝炎肝组织病理状态的性能。方法将324例HBeAg阳性和255例HBeAg阴性慢性乙型肝炎患者随机分为3组匹配的训练集和验证集。血清HBsAg和HBcrAg分别采用Abbott Architect I2000和Fujirebio Lumipulse G1200全自动化学发光免疫系统检测,血清HBV DNA采用Bio-Rad Icycler荧光定量PCR仪检测。肝组织病理学诊断采用Scheuer评分系统,其中病理学分级包括G0~G4五级,分期包括S0~S4五期。结果无论HBeAg阳性或阴性患者,3个训练集与3个匹配的验证集性别比例和平均年龄、病理学分级和分期构成比之间的差异均无统计学意义(P0.05)。HBeAg阳性患者,血清HBsAg、HBcrAg、HBV DNA预测全集病理学分级≥G3和分期≥S4的ROC曲线下面积最大;参照预测3个训练集病理学分级≥G3和分期≥S4的最佳截断值,血清HBsAg、HBcrAg、HBV DNA预测3个匹配的验证集病理学分级≥G3和分期≥S4的灵敏度极差分别为37%和9%、30%和16%、17%和14%,特异度极差分别为12%和5%、13%和3%、15%和6%。HBeAg阴性患者,血清HBcrAg、HBV DNA预测全集病理学分级≥G2和分期≥S2的ROC曲线下面积最大;参照预测3个训练集病理学分级≥G2和分期≥S2的最佳截断值,血清HBcrAg、HBV DNA预测3个匹配的验证集病理学分级≥G2和分期≥S2的灵敏度极差分别为11%和20%、46%和19%,特异度极差分别为15%和2%、38%和16%。结论 HBeAg阳性患者,血清HBsAg、HBcrAg、HBV DNA可预测的最佳病理状态为病理学分级≥G3和分期≥S4,其预测理学分期≥S4的稳定性高于预测病理学分级≥G3;HBeAg阴性患者,血清HBcrAg和HBV DNA可预测的最佳病理状态为病理学分级≥G2和分期≥S2,血清HBcrAg预测病理学分级≥G2和分期≥S2的稳定性高于HBV DNA。     

QIAGEN实时PCR与COBASTaqMan检测血清HBVDNA预测慢性乙型肝炎肝组织病理状态的性能比较

目的比较QIAGEN实时PCR与COBAS TaqMan检测血清HBV DNA水平预测慢性乙型肝炎肝组织病理状态的性能。方法慢性乙型肝炎患者278例,其中HBeAg阳性和阴性分别为162例和1 16例。采用QIAGEN实时定量PCR和COBAS TaqMan系统检测血清HBV DNA。肝组织病理学诊断采用Scheuer评分系统,其中病理学分级和分期包括G0~G4和S0~S4。结果血清HBV DNA(QIAGEN)和HBV DNA(C()BAS)在HBeAg阳性患者G2与G3,S1、S2、S3与S4之间的差异有统计学意义(P均0.05);在HBeAg阴性患者G1与G2、G3,S1与S2、S3、S4之间的差异有统计学意义(P均0.05)。血清HBV DNA(QIAGEN)与HBV DNA(COBAS)定量的不一致率,在HBeAg阳性患者G1-2、G3和S1-3、S4分别为4.24%(5/1 18)、9.09%(4/44)和3.68%(5/136)、7.69%(2/26),在HBeAg阴性患者G1、G2-3和S1、S2-4分别为6.02%(5/83)、3.03%(1/33)和3.29%(2/61)、3.64%(2/55)。血清HBV DNA(QIAGEN)和HBV DNA(COBAS)预测HBeAg阳性患者≥G3、≥S4的ROC曲线下面积分别为0.645和0.695、0.703和0.755,预测HBeAg阴性患者≥G2、≥S2的ROC曲线下面积分别为0.848和0.817、0.756和0.756。血清HBV DNA(QIAGEN)和HBV DNA(COBAS)预测HBeAg阳性患者≥S4的最佳截断值分别为≤3.784×10~6 IU/mL和≤6.668×10~7IU/mL,对应的灵敏度、特异度分别为0.654和1.000、0.735和0.581;预测HBeAg阴性患者≥G2的最佳截断值分别为≥5.821×10~3IU/mL和≥9.311×10~3 IU/mL,对应的灵敏度、特异度分别为0.970和0.909、0.614和0.651。结论血清HBV DNA预测肝组织病理状态的特点为预测HBeAg阴性患者≥G2的效能最大,并且血清HBV DNA(QIAGEN)与HBV DNA(COBAS)预测HBeAg阴性患者≥G2的性能有高度一致性。     

血清HBsAg和HBV DNA预测慢性乙型肝炎肝组织病理状态的评价

目的 探讨血清乙型肝炎表面抗原（HBsAg）水平和乙型肝炎病毒DNA（HBV DNA）载量预测慢性乙型肝炎（CHB）肝组织炎症活动度和纤维化程度的效能.方法 472例经肝组织活检的CHB患者入选本研究,其中HBeAg阳性279例,HBeAg阴性193例.肝组织病理学分级≥G2、≥G3、≥G4分别被定义为显著炎症、严重炎症和进展期炎症,病理学分期≥S2、≥S3和≥S4分别被定义为显著纤维化、严重纤维化和进展期纤维化.结果 HBeAg阳性患者血清HBsAg在G1与G3、G2与G3、S1与S4、S2与S4、S3与S4之间的差异均有统计学意义（P均＜0.05）,血清HBV DNA载量在S1与S4、S2与S4、S3与S4之间的差异均有统计学意义（P均＜0.05）;HBeAg阴性患者血清HBsAg在肝组织不同病理学分级和分期之间的差异无统计学意义（P＞0.05）,血清HBV DNA载量在G1与G3、S1与S2、S1与S3、S1与S4之间的差异均有统计学意义（P均＜0.05）.HBeAg阳性患者血清HBsAg诊断严重炎症和进展期纤维化的ROC曲线下面积分别为0.711 （95％ CI：0.647～0.775）和0.765（95％ CI：0.707～0.823）,血清HBV DNA诊断严重炎症和进展期纤维化的ROC曲线下面积分别为0.589（95％ CI：0.519 ～0.659）和0.700（95％ CI：0.632 ～0.769）;HBeAg阴性患者血清HBV DNA诊断非显著炎症和非显著纤维化的ROC曲线下面积分别为0.644（95％ CI：0.565 ～0.723）和0.684（95％ CI：0.606～0.761）.结论 血清HBsAg对HBeAg阳性患者肝组织严重炎症和进展期纤维化有一定的预测价值;血清HBV DNA对HBeAg阳性患者肝组织严重炎症和进展期纤维化和对HBeAg阴性患者肝组织非显著炎症和非显著纤维化有一定的预测价值.     

学龄前HBeAg阴性慢性乙型肝炎患儿临床特点分析

目的 探讨学龄前乙型肝炎e抗原(HBeAg)阴性慢性乙型肝炎患儿临床特点。方法 回顾性分析我院2018年5月—2019年5月收治的115例学龄前慢性乙型肝炎患儿的临床资料。依据HBeAg检查结果分为观察组(HBeAg阴性,n=46)与对照组(HBeAg阳性,n=69例)。对比两组基础资料、实验室检查结果[性别、年龄、病程、家族史、谷丙转氨酶(ALT)、谷草转氨酶(AST)、慢性乙型肝炎病毒(HBV DNA)]及肝组织炎症活动分级、肝纤维化分期。结果观察组性别、年龄、家族史、ALT、AST与对照组对比无显著差异(P0.05);观察组病程显著长于对照组,HBV DNA水平显著低于对照组,差异有统计学意义(P0.05)。观察组肝组织炎症活动分级以G3、G4级为主,对照组肝组织炎症活动分级以G1、G2级为主,组间对比差异有统计学意义(P0.05)。观察组肝纤维化分期以S3、S4期为主,对照组肝纤维化分期以S0、S1、S2期为主,组间对比差异有统计学意义(P0.05)。结论 学龄前HBeAg阴性慢性乙型肝炎患儿具有病程长、HBV DNA水平低的特点,且HBeAg阴性患儿更容易出现肝纤维化和病情持续恶化。     

拉米夫定治疗HBeAg阳性慢性乙型肝炎患者病毒学反弹的多因素分析

我们观察了用拉米夫定治疗HBeAg阳性慢性乙型肝炎145例患者2年的疗效,分析了病毒学反弹(VB)与患者基线肝组织炎性活动度分级(G)、纤维化分期(S)、ALT水平、HBV DNA载量及疗程12,24周时病毒学应答的关系,现报道如下.     

HBeAg阴性和阳性慢性乙型肝炎患者血清HBV DNA水平与肝组织炎症的关系

目的:探讨HBeAg阴性和HBeAg阳性慢性乙型肝炎(CHB)HBVDNA水平和肝组织炎症损害的关系.方法:采用荧光定量聚合酶链反应分别对331例CHB(101例HBeAg阴性和230例HBeAg阳性)患者进行血清HBVDNA定量检测和肝组织活检病理炎症分级,对比分析结果.结果:331例CHB患者血清HBVDNA水平与肝组织炎症活动度及肝纤维化程度之间无明显相关性;101例HBeAg阴性CHB患者中31例(31%)血清HBVDNA>108copies/L,随着G1-G4肝组织炎症损害级别的增高其所占例数也相应增高.HBVDNA水平与肝组织炎症病理分级的相关性有显著意义(r=0.271,P<0.005);在230例HBeAg阳性的患者中,血清HBVDNA水平与肝组织炎症呈明显的负相关(r=-0.659,P<0.001).结论:血清HBVDNA水平可作为判断HBeAg阴性CHB患者肝组织炎症损害程度的指标,在HBeAg阳性的患者中,血清HBVDNA水平与肝组织炎症呈负相关.     

慢性乙型肝炎患者血清HBeAg和HBV DNA水平与肝组织病理关系的探讨

目的　探讨慢性乙型肝炎患者血清HBeAg、HBVDNA水平与肝组织病理分级分期的关系。方法　应用微粒子荧光免疫分析法 (MEIA)及荧光定量聚合酶链反应法 (PCR)对 167例慢性乙型肝炎患者血清进行HBeAg和HBVDNA定量检测 ,并与同期肝组织活检病理结果对比分析。结果　慢性乙型肝炎患者血清HBeAg定量与病理分级分期有明显相关性 (r =0 .48,p <0 .0 5 ;r =0 .5 3 5 ,p <0 .0 5 ) ,而血清HBVDNA定量与病理分级分期无明显相关性 (r =0 .0 45 ,p =0 .717;r =0 .10 5 ,p =0 .3 83 )。慢性乙型肝炎患者血清HBeAg与HBVDNA定量水平有良好的一致性 (r =0 .5 3 3 ,p <0 .0 5 )。结论　肝组织学炎症分级及纤维化分期与HBeAg定量相关。随着血清HBeAg定量降低 ,肝组织炎症活动加重 ,肝组织纤维化程度升高 ;HBVDNA定量与肝组织炎症及纤维化无明显关系。根据测定慢性乙型肝炎患者血清HBeAg定量的变化 ,可以初步估计肝实质受损情况。结合HBVDNA定量的检测 ,可以为临床判断病情变化、严重程度、HBV前C区变异的初筛及抗病毒治疗方案的选择提供有价值的参考。     

慢性乙型肝炎病毒携带者肝组织学特点与临床特征的关系

目的研究慢性HBV携带者的肝组织学特点与其临床特征的关系。方法对以“慢性HBsAg携带者”入院的142例患者行肝脏活体组织学检查,平均年龄（24．8±8．7）岁;其中129例血清HBV DNA阳性,符合“慢性HBV携带者”诊断,余13例符合“非活动性HBsAg携带者”诊断。肝穿刺获取标本（2．2±0．8）cm以进行组织学检查;同时进行血清病毒学、纤维化指标及蛋白质电泳、超声检查。按血清HBV DNA是否阳性及病理学诊断分组比较。结果病理学检查肝组织正常（G0S0）36例,慢性肝炎[炎症分级≥G1和（或）纤维化分期≥S1]106例,其中包括早期肝硬化（G4S4）1例;按HBV DNA是否阳性分组比较,差异无统计学意义。血清HBV DNA均值为（7．58±0．99）log10拷贝／ml,HBeAg阳性123例。45．8％（49／107）γ-球蛋白增高;37．1％（23／62）血清纤维化指标增高;40．1％（57／142）彩色多普勒超声检查显示异常。按病理学诊断分组比较,慢性肝炎组的血清PCⅢ均值高于正常组（P〈0．05）;PCⅢ与炎症分级呈正相关（r=0．391, P〈0．01）。结论本组病例具有高病毒载量及炎症轻微的特征;组织学炎症分级、纤维化分期与HBV DNA水平及HlBeAg状态无相关性,血清PCⅢ增高与炎症分级有关。     

Prognostic analysis in chronic hepatitis B patients: a retrospective study of 216 cases about Scheuer scores, in situ expression of viral antigens and tissue hepatitis B virus DNA levels.

BACKGROUND: Most of the previous studies of patients with chronic hepatitis B virus (HBV) infection concentrated on serum samples. Liver biopsy specimens for HBV have not been systematically analyzed. This study was performed to analyze some histopathological indicators (Scheuer scores, the expression of HBV antigens in situ, HBV DNA quantification) in the biopsy samples and showed the relationship among them and the prognosis of chronic hepatitis. METHODS: A total of 216 consecutive chronic HBV-infected patients were followed up by clinical and laboratory data and classified into two groups at first: carcinogenesis and non-carcinogenesis. The non-carcinogenesis also included two groups: cirrhosis and non-cirrhosis. The non-cirrhosis was still divided into fluctuation and normalization at last. Histological activity index was described by Scheuer scores. Two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by fluorescence quantitative real-time PCR. RESULTS: Regression analysis revealed significant positive correlations between the expression of hepatitis B e antigen (HBeAg) and grading, as well as between hepatitis Bx (HBx) protein and grading or staging of Scheuer scores. Positive correlations between grading or staging and prognosis were statistically significant. The expressions of HBeAg and HBx protein were higher in patients with cirrhosis than those without cirrhosis. Scheuer score was the most important indicator of prognosis. CONCLUSIONS: HBeAg and HBx protein can be used as indicators of hepatitis activity and their positive expressions increase the risk for cirrhosis remarkably. In addition to be a marker of liver damage, Scheuer score is the most reliable indicator of the prognosis.     

Quantitative detection of hepatitis B virus DNA in sera from patients with acute hepatitis B

Two hundred forty-four serial serum samples from 30 adults hospitalized with benign (nonfulminant) acute hepatitis B were tested for the presence of hepatitis B virus (HBV) DNA by a quantitative solution hybridization assay using a¹²⁵I-labeled DNA probe complementary to HBV-DNA sequences. Acute hepatitis B was self-limiting in 28 and progressed to chronicity in the remaining two patients. Of the 28 patients with self-limiting hepatitis, 21 (75%) were hepatitis B e antigen (HBeAg) positive, 26 (93%) were HBV-DNA positive, and one patient (3.6%) was negative for both markers on admission to the hospital. HBV-DNA cleared after HBeAg clearance in 20 (71.4%), before HBeAg clearance in five (17.9%) and simultaneously with the loss of HBeAg in the remaining two (7.1%) of the 27 initially HBV-DNA- and/or HBeAg-positive patients. Moreover, HBV-DNA remained detectable in serum for 13.3±6.6 (range: 4–22) days after the appearance of anti-HBe in 71.4% of these patients. In contrast, HBV-DNA and HBeAg remained persistently positive in the two patients who developed chronic HBV infection. These data show that: (1) viremia frequently persists after disappearance of HBeAg and (2) appearance of anti-HBe does not indicate the cessation of HBV replication in adults with acute self-limiting hepatitis B.     

Chronic persistent hepatitis type B can be a progressive disease when associated with sustained virus replication

In 44 hepatitis B virus (HBV) carriers with chronic persistent hepatitis (CPH), serial liver biopsies were available. At presentation 38 patients had HBV-DNA in their serum including 31 HBeAg positive and seven anti-HBe positive cases. The remaining six patients were anti-HBe positive and HBV-DNA negative. During a mean histologic follow-up of 4.2 years, 12 (32%) of the 38 HBV-DNA positive patients progressed to chronic active hepatitis (six cases) or to active cirrhosis (six cases), while 26 patients showed either unchanged features of CPH (21 cases), or histologic improvement to normal liver (five cases). Persistence of HBV-DNA in serum, independently of HBeAg/anti-HBe events, was significantly (p less than 0.01) associated with deterioration of liver disease, while termination of HBV replication correlated significantly (p less than 0.05) with spontaneous biochemical remission and with unchanged or improved histology. None of the six anti-HBe positive patients without serologic markers of hepatitis B virus replication showed histologic deterioration. These findings indicate that continuing HBV replication is a marker which predicts unfavourable evolution of chronic persistent hepatitis and frequent transition to chronic active hepatitis or cirrhosis.     

慢性乙型肝炎患者肝组织HBV cccDNA、总HBV DNA与血清HBV DNA的相关性及其与临床的关系

目的探讨慢性乙型肝炎患者肝组织HBV共价闭合环状DNA（cccDNA）、肝组织总HBV DNA（HBV tDNA）与血清HBV DNA之间的相关性及其与临床的关系。方法 78例慢性乙型肝炎患者入选本研究。肝组织β- globinDNA、HBV cccDNA和HBV tDNA采用实时荧光定量PCR方法检测,平均每个肝细胞HBV cccDNA和HBV tDNA含量（拷贝/cell）=HBV cccDNA（实测值）/β-globin DNA（实测值）和HBV tDNA（实测值）/β3-globin DNA（实测值）,肝组织HBV cccDNA和HBV tDNA含量的计算单位定义为log₁₀拷贝/10⁶cell;采用实时荧光定量PCR、ELISA法检测血清HBVDNA和HBV标志物;采用免疫组织化学方法检测肝细胞中HBsAg和HBcAg的表达。统计分析采用pearson相关分析及t检验。结果 （1）肝组织HBV cccDNA与HBV tDNA定量呈正相关（r=0.696,P<0.001）;肝组织HBV cccDNA与血清HBV DNA定量呈正相关（r=0.304,P<0.01）;肝组织HBV tDNA与血清HBV DNA定量呈正相关（r=0.341,P<0.01）;（2）肝细胞内HBcAg定性检测阳性患者的血清HBV DNA定量明显高于阴性患者,且差异有统计学意义（P<0.05）;肝细胞内HBcAg定性检测阳性患者与阴性患者的肝组织HBV cccDNA和HBV tDNA定量差异均无统计学意义和（P均>0.05）;（3）肝细胞内HBsAg定性检测阳性患者的血清HBV DNA定量明显高于阴性患者,且差异有统计学意义（P<0.05）;肝细胞内HBsAg定性检测阳性患者与阴性患者的肝组织HBV cccDNA和HBV tDNA定量差异均无统计学意义（P>0.05）;（4）HBeAg（+）/抗-HBe（-）患者血清HBV DNA定量明显高于HBeAg（-）/抗-HBe（+）患者,且差异有统计学意义（P<0.05）;HBeAg（+）/抗-HBe（-）患者肝组织HBV cccDNA和HBV tDNA定量与HBeAg（-）/抗-HBe（+）患者比较差异均无统计学意义（均P>0.05）;（5）肝组织HBV cccDNA、HBV tDNA以及血清HBV DNA三者与肝脏炎症活动度及纤维化程度均无显著相关性（P>0.05）。结论 （1）血清HBV DNA定量结果并不一定能完全反映患者肝组织中HBV cccDNA和HBV tDNA含量,尤其在血清HBV DNA<500拷贝/mL时,肝组织中仍存在HBV cccDNA和HBV tDNA,且含量大小不等。（2）肝细胞内HBcAg定性检测阳性或者HBsAg定性检测阳性患者的血清HBV DNA定量均明显高于阴性患者;而两者的肝组织HBV cccDNA和HBV tDNA定量均没有显著差异;（3）HBeAg（+）/抗-HBe（-）患者血清HBV DNA定量明显高于HBeAg（-）/抗-HBe（+）患者,而两者的肝组织HBV cccDNA和HBV tDNA均没有显著差异;（4）肝组织HBV cccDNA、HBV tDNA及血清HBV DNA与肝脏炎症活动度和纤维化程度均无显著相关性。     

Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti-HBe in chronic hepatitis type B

Seventy consecutive HBsAg- and HBeAg-positive patients with biopsy-proven chronic hepatitis were followed prospectively with serial determinations of SGPT levels and hepatitis B virus serum markers including HBsAg, HBeAg, anti-HBe and hepatitis B virus DNA. During a period of 1 to 11 years (mean +/- S.D.: 5.0 +/- 2.3 years), 28 patients remained persistently HBeAg positive, most with continuing biochemical and histologic activity, while 41 cases seroconverted to anti-HBe. One patient became HBeAg and anti-HBe negative. After seroconversion, 87.8% of the cases showed sustained normalization of SGPT, and clearance of hepatitis B virus DNA from serum and histologic improvement was documented in 79% of the cases who had a control liver biopsy, while 15.8% developed cirrhosis. In two patients (4.9%), the disease remained active despite seroconversion, and both cases had evidence of continuing hepatitis B virus replication. Finally, reactivation of liver damage and of hepatitis B virus replication was observed in three additional patients (7.3%) who had transiently normalized SGPT after seroconversion. All 70 patients were analyzed for hepatitis delta virus markers, and only two persistently HBeAg-positive cases were found positive for antibody to hepatitis delta virus in serum, one also having hepatitis delta antigen in the liver. These findings indicate that, in chronic hepatitis type B, termination of virus replication is associated in most patients with biochemical and histologic regression of inflammatory activity. After anti-HBe seroconversion has occurred, virus replication and liver disease may persist or reactivate in a small proportion of patients thus giving origin to the well-recognized group of anti-HBe positive, hepatitis B virus DNA-positive chronic hepatitis type B.