乙型肝炎患者血清Pre-S-2抗原的意义

目的研究ＰｒｅＳ２抗原与乙型肝炎患者ＨＢＶ标记的关系．方法血清ＨＢｓＡｇ（＋），ＨＢｅＡｇ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者２６例，血清ＨＢｓＡｇ（＋），ＨＢｅＡｂ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者４７例及健康献血者２０例，血清用ＲＩＡ法检测ＰｒｅＳ２抗原及用ＰＣＲ法检测ＨＢＶＤＮＡ．结果血清ＨＢｓＡｇ（＋），ＨＢｅＡｇ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者２６例，ＰｒｅＳ２抗原与ＨＢＶＤＮＡ均阳性（１００％）；血清ＨＢｓＡｇ（＋），ＨＢｅＡｂ（＋），ＨＢｃＡｂ（＋）的乙型肝炎患者４７例，ＰｒｅＳ２抗原３０例阳性（６３８％），１７例阴性（３６２％），ＨＢＶＤＮＡ３２例阳性（６８１％），１５例阴性（３１９％），ＰｒｅＳ２抗原与ＨＢＶＤＮＡ均阳性２８例（５９６％），均阴性１４例（３００％）．健康献血者２０例，ＰｒｅＳ２抗原阳性１例（５０％），阴性１９例（９５０％），ＨＢＶＤＮＡ阳性２例（１００％），阴性１８例（８００％），ＰｒｅＳ２抗原及ＨＢＶＤＮＡ均阳性０例（０％），均阴性１８例（８００％）．结论ＰｒｅＳ２抗原可作为预测慢性乙型肝炎患者病情活动与传染的标志．     

PCR检测HBV感染患者血清HBV DNA的临床意义

目的探讨急、慢性乙型肝炎及与ＨＢＶ感染相关的肝硬变和肝癌患者血清ＨＢＶＤＮＡ的临床意义．方法应用ＰＣＲ技术检测不同ＨＢＶ感染２０５例，患者血清ＨＢＶＤＮＡ，并与正常人２０例作比较．结果ＨＢＶ感染患者２０５例血清ＨＢＶＤＮＡ阳性率为６９３％，慢性乙肝、乙肝后肝硬变和肝癌患者的阳性率分别为７６４％，７１９％和７００％，显著高于急性乙肝患者２１７％的阳性率（Ｐ＜００１）；ＨＢｅＡｇ（＋）患者血清ＨＢＶＤＮＡ阳性率为９３６％，显著高于ＨＢｅＡｇ（－）抗ＨＢｅ（＋）／（－）和ＨＢｓＡｇ（－）患者的阳性率（４５６％，２５０％和１２５％，Ｐ＜００１）；血清ＨＢＶＤＮＡ阳性和阴性两组患者的血清ＡＬＴ水平无明显差异（Ｐ＞００５）．结论血清中ＨＢＶＤＮＡ持续存在可能与乙型肝炎的慢性化有关，而与ＨＢＶ感染患者的肝损伤无明显关系     

PCR检测献血员乙肝感染状况

目的对部分献血员中乙型肝炎感染状况进行调查．方法用ＰＣＲ法对检查合格的２９０份献血血样进行ＨＢＶ＿ＤＮＡ检测．结果本组２９０份血样中ＨＢｓＡｇ，ＨＢｅＡｇ全部呈阴性．１６７例ＨＢＶＭ阳性；其中８０例单项抗ＨＢｓ阳性，５０例单项抗ＨＢｃ阳性，１９例抗ＨＢｓ和ＨＢｃ两项阳性，１２例抗ＨＢｅ和抗ＨＢｃ两项阳性；６例抗ＨＢｓ，抗ＨＢｅ和抗ＨＢｃ三项阳性，而ＨＢＶ－ＤＮＡ的阳性率在各组中分别为８８％（７／８０），２６０％（１３／５０），１０５％（２／１９），７５０％（９／１２），３３３％（２／６）．１２３例ＨＢＶＭ阴性，ＨＢＶ－ＤＮＡ的阳性率为１６％（２／１２３）．２９０例中ＨＢＶ－ＤＮＡ的总检出率为１２１％（３５／２９０）．结论合法献血员中存在着乙肝病毒感染者．     

血清HBeAg阴性与HBeAg/IC及A1896变异的关系

目的探讨血清ＨＢｅＡｇ阴性（双抗体夹心法）与ＨＢｅＡｇ／ＩＣ形成及ＨＢＶ变异株Ａ１８９６的关系，评价ＨＢｅＡｇ／ＩＣ检测的临床意义．方法单克隆抗ＨＢｅ固相ＥＬＩＳＡ检测血清中ＨＢｅＡｇ／ＩＣ；套式多聚酶链反应检测ＨＢＶＤＮＡ；３＇碱基特异多聚酶链反应判断Ａ１８９６变异；ＥＬＩＳＡ检测ＨＢｅＡｇ、抗ＨＢｅ，研究对象为１１７例慢性ＨＢＶ感染者，２０例健康对照统计处理采用卡方检验．结果ＨＢｅＡｇ／ＩＣ阳性血清中ＨＢＶＤＮＡ检出率明显高于ＨＢｅＡｇ／ＩＣ阴性血清，Ｐ＜０００１（９１３％ｖｓ３６２％）；２９份ＨＢｅＡｇ阴性、ＨＢＶＤＮＡ阳性血清中仅５例（１７２％）检出Ａ１８９６，而且其中２例与野毒株（Ｇ１８９６）混合感染并伴ＨＢｅＡｇ／ＩＣ阳性．２９份中１７份（５８７％）为ＨＢｅＡｇ／ＩＣ阳性的Ｇ１８９６感染；血清抗ＨＢｅ阳性组Ａ１８９６检出率高于抗ＨＢｅ阴性组，Ｐ＜００５（２５％ｖｓ３２％）．结论ＨＢｅＡｇ／ＩＣ为ＨＢＶ活跃复制指标；临床ＨＢｅＡｇ阴性、ＨＢＶＤＮＡ阳性患者仍多数为Ｇ１８９６感染，ＨＢｅＡｇ／ＩＣ形致双抗体夹心法不能检出ＨＢｅＡｇ；抗ＨＢｅ应答可能为促使前Ｃ变异的重要因素     

HBV 侵犯PBMC致线粒体功能改变

目的探讨ＨＢＶ侵犯外周血单个核细胞（ＰＢＭＣ）后对其线粒体功能的影响．方法ＨＢｓＡｇ阳性６个月以上，无肝炎症状及体征，肝功正常患者５８例．多聚酶链反应检测ＰＢＭＣ中ＨＢＶＤＮＡ，噻唑兰（ＭＴＴ）比色法测线粒体功能．ＨＢｓＡｇ、ＨＢｅＡｇ检测用固相放免法检测．结果慢性ＨＢＶ感染者５８例，ＰＢＭＣ中检出ＨＢＶＤＮＡ３１例（５３５％），ＰＢＭＣ中ＨＢＶＤＮＡ阳性组ＭＴＴ比色法查线粒体功能的Ａ（ＯＤ５００ｎｍ）值明显低于ＨＢＶＤＮＡ阴性组（００５±００３ｖｓ０２９±００７，Ｐ＜００１）．结论慢性ＨＢＶ感染时，ＨＢＶ常侵犯ＰＢＭＣ，并导致ＰＢＭＣ线粒体功能降低、能量代谢异常．这可为ＨＢＶ慢性感染免疫功能异常的原因之一．     

慢性乙型病毒性肝炎的幽门螺杆菌感染

目的由于慢性乙型肝炎（乙型肝炎）时幽门螺杆菌（Ｈｐ）感染的报道罕见，因而本研究旨在探讨乙型肝炎患者的Ｈｐ感染状态．方法乙型肝炎患者４４例，采用酶联免疫吸附试验检测血清乙型肝炎病毒（ＨＢＶ）标志物，并采用聚合酶链反应测定ＨＢＶＤＮＡ来确定ＨＢＶ感染．同时通过血清学、尿素酶试验、组织学染色和细菌培养，进行Ｈｐ检查．结果乙型肝炎患者的消化性溃疡发生率为１３６％（６／４４）；Ｈｐ感染率为６１４％（２７／４４）．ＨＢｅＡｇ和（或）ＨＢＶＤＮＡ阳性者Ｈｐ感染率为６３０％（１７／２７），高于ＨＢｅＡｇ和ＨＢＶＤＮＡ皆阴性者的３５３％（６／１７）．此外，以组织学染色确定Ｈｐ感染的阳性率最高．结论乙型肝炎患者Ｈｐ感染率高，可能是引起乙型肝炎患者消化性溃疡发生的重要原因     

乙型肝炎患者外周血单个核细胞对HBV不同区抗原的增殖反应

目的进一步明确外周血细胞免疫在ＨＢＶ感染过程中的作用。方法对２０例急性乙型肝炎（乙肝）患者、２３例慢性乙肝患者、２０例正常献血员进行了研究,用氮蓝四唑实验（ＭＴＴ）测定乙肝患者外周血单个核细胞（ＰＢＭＣ）对ＨＢＶ不同区抗原的增殖反应。结果在急性乙肝患者ＰＢＭＣ对抗原的增殖反应大于慢性乙肝患者及正常对照,ＰＢＭＣ对ＨＢｃＡｇ的增殖反应最高,ＨＢｅＡｇ次之,而对ＨＢｓＡｇ的反应均较弱。另外,无论在急性、慢性患者,其ＰＢＭＣ对抗原的增殖反应水平与血清丙氨酸转氨酶（ＡＬＴ）的变化无明显相关性。血清ＨＢＶＤＮＡ阴性、ＨＢｅＡｇ阴性的慢性肝炎或慢性肝炎急性发作患者,其ＰＢＭＣ对ＨＢＶ抗原的增殖反应较弱,在血清ＨＢＶＤＮＡ或ＨＢｅＡｇ阳性患者,增殖反应较强,而当血清ＨＢＶＤＮＡ、ＨＢｅＡｇ均阳性时,增殖反应最强,表明外周细胞免疫与ＨＢＶ的复制及清除相关。结论ＨＢＶ感染后,外周血中存在对ＨＢＶ抗原的细胞免疫,这种细胞免疫可能与乙肝的发病及ＨＢＶ的清除有关。     

芹灵冲剂治疗慢性乙型肝炎102例的临床研究

目的观察芹灵冲剂对慢性乙型肝炎患者的治疗效果．方法慢性乙型肝炎患者１０２例，应用芹灵冲剂（水芹等两味中药组成）进行治疗，男８４例，女１８例；年龄１６岁～５４岁，其中２０岁～４５岁８７例（７７４％）；病程６ｍｏ～５ａ，其中１ａ～４ａ者７８例（６５６％）；全部病例治疗前肝功能均不正常，ＨＢｓＡｇ、ＨＢｅＡｇ和抗ＨＢｃ均为阳性，食少纳差，全身无力等．治疗组服药１～２包（相当生药１０ｇ／包），３次／ｄ，３０ｄ为１疗程，一般２～３个疗程．对照组６０例，男３５例，女２５例；年龄２０岁～６５岁．治疗前肝功能均不正常，ＨＢｓＡｇ、ＨＢｅＡｇ和抗ＨＢｃ均为阳性；病程６ｍｏ～６ａ；服用益肝灵４片，３次／ｄ，疗程同上．每疗程结束后两组患者均复查肝功能和乙肝抗原抗体一次．在治疗中均辅用葡萄糖，维生素Ｃ，能量合剂等保肝药物．结果经芹灵冲剂治疗２～３疗程后，显效４６例，有效５３例，无效３例，总有效率为９７１％．所有病例降酶率为９６１％，退黄率为９８０％；ＨＢｓＡｇ转阴率为４５１％、ＨＢｅＡｇ为５３９％，抗ＨＢｃ为４８６％．服药期间未见明显毒副反应．结论芹灵冲剂对慢性乙型肝炎患者具有退黄降酶、抗乙肝病毒的良好效果．     

拉米夫定治疗HBeAg阴性的慢性HBV感染近期临床观察

观察和评价拉米夫定治疗ＨＢｅＡｇ阴性慢性ＨＢＶ感染的近期疗效。ＨＢｅＡｇ阴性／ＨＢＶ ＤＮＡ阳性的慢性ＨＢｖ感染者２６例（包括１１例乙肝肝硬化），ＨＢｅＡｇ阳性／ＨＢＶ　ＤＮＡ阳性的慢性ＨＢＶ感染者３０例（包括１０例乙肝肝硬化），均以拉米夫定治疗６个月后进行疗效评价，并继续观察５－１６个月。两组的ＡＬＴ／ＡＳＴ复常率分别为８４．７％／８８．５％和８６．７％／８６．７％（Ｐ＞０．０５），肝硬化患者Ｃｈｉｌｄ－Ｐｕｇｈ积分均明显下降，ＨＢＶ　ＤＮＡ全部阴转。ＨＢｅＡｇ阳性组３例发生ＹＭＤＤ变异，ＨＢｅＡｇ阴性组无１例变异。拉米夫定对于ＨＢｅＡｇ阴性／ＨＢＶ　ＤＮＡ阳性者，同样是十分安全有效的抗病毒治疗药物。ＨＢｅＡｇ阴性者的耐药发生率可能低于ＨＢｅＡｇ阳性者。     

血清抗-HBs阳性慢性肝病患者的病因研究

目的部分抗－ＨＢｓ阳性者仍有活动性肝病存在，其病因还不十分清楚．本研究旨在探讨血清抗ＨＢｓ阳性慢性肝病患者的病因．方法应用套式聚合酶链反应检测血清抗ＨＢｓ阳性慢性肝病患者血清中ＨＢＶＤＮＡ和ＨＣＶＲＮＡ．患者３２例，男２５例，女７例，平均年龄４１７岁（２１岁～６３岁），其中慢性肝炎１８例，肝硬变１４例．９例慢性肝炎和５例肝硬变经肝活检证实，其余为临床诊断．结果血清中ＨＢＶＤＮＡ和ＨＣＶＲＮＡ的检出率分别为６２５％（２０／３２）和２８１％（９／３２）；ＨＢＶＤＮＡ和（或）ＨＣＶＲＮＡ总检出率为８１３％（２６／３２）．结论血清抗ＨＢｓ阳性慢性肝病患者的病因多数与ＨＢＶ和（或）ＨＣＶ感染有关．     

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

AIM: To study the intrahepatic expression of hepatitis B surface antigen(HBs Ag) and hepatitis B core antigen(HBc Ag) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients(mean age of 40.3 ± 2.5 years), comprising of 14 HBe Ag positive and 19 HBe Ag negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma(mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBc Ag and HBs Ag was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBc Agand HBs Ag staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBe Ag negative patients, the HBe Ag positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBe Ag positive patients had intrahepatic HBc Ag staining; predominantly with "diffuse" distribution(79%) and "mixed cytoplasmic/nuclear " pattern(79%). In comparison, only 5% of the HBe Ag-negative patients had intrahepatic HBc Ag staining. However, the intrahepatic HBs Ag staining has wider distribution among the HBe Ag negative patients, namely; majority of the HBe Ag negative cases had "patchy" HBs Ag distribution compared to "rare" distribution among the HBe Ag positive cases. All but one patient with HCC were HBe Ag negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBc Ag and HBs Ag were seen in 13(100%) and 10(77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBc Ag and HBs Ag were detected in tumor tissues but not the adjacent liver in 4(44%) and 1(11%) patient respectively. CONCLUSION: Isolated intrahepatic HBc Ag and HBs Ag can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.     

联合检测HBV前S1抗原和核心抗原的临床意义

探讨联合检测血清HBV前s1抗原（preSl）和核心抗原（HBcAg）（均为HBV核酸相关抗原，nucleic acids related antigen，HBV NRAg）的意义及临床价值。方法：采用ELISA法对393份HBsAg、HBV DNA双阳性的血清和612份HBsAg阴性血清进行HBV NRAg检测，所有标本均采用多区段巢式PCR确认阳性、阴性，采用荧光定量PCR法进行HBV DNA定量分析。结果：393份HBsAg、HBV DNA双阳性血清中，HBV NRAg阳性为382份，其阳性率为97．2％；612份HBsAg阴性的血清标本中，609份确认为HBV DNA阴性，其中检出2份HBV NRAg阳性，607份为阴性，其HBV NRAg的阴性率为99．7％（607／609），另3份HBsAg阴性血清HBV DNA阳性者，其HBV NRAg均为阳性。结论：联合检测preSl和HBcAg的HBV NRAg可作为临床HBV感染的筛选及判断HBV复制的有意义的补充项目。     

Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir

Background and Aim: We investigated whether intrahepatic markers could predict response in chronic hepatitis B virus (HBV) patients treated with peg‐interferon and adefovir for 48 weeks. Methods: Intrahepatic covalently closed circular DNA (cccDNA), total intrahepatic HBV DNA and the proportion of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) positive hepatocytes in 16 hepatitis B e antigen (HBeAg) positive and 24 HBeAg negative patients were measured at baseline and at end of treatment. Results: Baseline intrahepatic markers were not associated with sustained virological response (SVR) defined as HBV DNA < 2000 IU/mL and persistent normal alanine aminotransferase levels at the end of follow‐up (week 72). At end of treatment, intrahepatic cccDNA and total intrahepatic HBV DNA in HBeAg positive patients were significantly lower in patients with HBeAg seroconversion (P = 0.016 and P = 0.010) with positive predictive values (PPV) for SVR of 80% and 80%, respectively. In HBeAg negative patients, intrahepatic cccDNA and total intrahepatic HBV DNA had declined significantly at end of treatment (P = 0.035 and P = 0.041) and corresponding PPV for SVR was 73% and 82%. In HBeAg positive patients, median proportion of HBcAg positive hepatocytes declined significantly (P = 0.002) at end of treatment. In HBeAg negative patients, the proportion of HBsAg positive hepatocytes had declined significantly at end of treatment (P = 0.0009). Using HBsAg ≤ 7.5% as a limit, PPV for SVR in HBeAg negative patients was 83%. Conclusions: At end of treatment in HBeAg positive patients, intrahepatic cccDNA and total intrahepatic HBV DNA were predictive for SVR. In HBeAg negative patients a proportion of < 7.5% HBsAg positive hepatocytes at end of treatment was a strong predictor for SVR.     

HBsAg定量预测干扰素治疗e抗原阳性慢性乙型肝炎的远期疗效

目的观察血清中的HBsAg水平与e抗原的血清转换率的关系,预测干扰素的远期疗效。方法 86例e抗原阳性慢性乙型肝炎（CHB）患者按照治疗前HBsAg定量〈100、100~200、〉200 ng/L分为3组,均给予干扰素抗病毒治疗12个月。对照组18例,未予干扰素治疗。在不同治疗时间分别检测血清ALT、HBV DNA、HBsAg、HBeAg和HBcAb,并计算治疗3个月时HBsAg抑制率,按照其≥50%和〈50%分为2组,观察治疗终点时e抗原的血清转换率、HBsAg阴转率和HBV DNA阴转率。结果治疗终点时,三个层次的干扰素治疗组和对照组e抗原的血清转换率分别为58.5%、37.3%、20.0%和5.6%,HBsAg的阴转率分别为54.5%、15.6%、6.7%和0,HBVDNA的血清阴转率分别为70.8%、34.4%、23.3%和0。e抗原的血清转换率与HBsAg初始水平和治疗3个月时下降幅度有相关性。结论 HBsAg初始水平或治疗3个月后下降幅度是获得较高e抗原的血清转换率较好的预测指标,有助于指导临床用药。     

肝移植后乙型肝炎病毒再感染的预防与治疗

目的；研究肝移植后再感染的预防和治疗。方法：19例患者包括慢性乙型重型肝炎，终末期肝硬化和肝硬化合并肝癌患者，移植前，后给予抗,乏昔洛韦4例，拉米夫定13例，拉米夫定＋乙型肝炎免疫球蛋白（HBIg) 2例，观察临床表现，血HBV M及肝活检免疫组织化学等指标。结果：应用乏昔洛韦治疗的4例患者全部再感染，血清HBsAg,HBeAg和HBV DNA均阳性，3例患者肝活检免疫组织化学表现有HBsAg ,HBcAg表达，随病程延长而增多。1例发生了典型病毒性肝炎发病。4例中3例死亡，拉米夫定的治疗组13例，经治疗后仅有7例HBsAg阳性，2例HBV DNA阳性，4例肝组织免疫组织化学有HBsAg或HBcAg表达，治疗中1例有肝炎复发。拉米夫定＋HBIg治疗2例患者1例血清抗－HBc阳性，另1例HBV M均阴性。免疫组织化学检测亦未见阳性结果。结论：HBV感染相关疾病终末期肝病应作为肝移植的适应证，肝移植后抗病毒治疗可预防再感染，改善再感染者的预后。     

抗—HBs阳性不同血清学模式病毒学及临床意义分析

目的：通过对抗－HBs阳性不同血清学模式病毒学和临床意义的分析,了解抗－HBs阳性不同血清学模式特点,探讨其形成机理及抗－HBs的作用。方法：采用Abbott和PCR定量、PCR定性方法分别检测抗－HBs阳性不同血清学模式病人的HBV血清标志物和HBV DNA。结果：抗－HBs、抗－HBe、抗－HBc阳性组与其它模式组比较,其抗－HBs值显著升高（P＜0．05）;HBsAg、抗－HBs、HBeAg阳性组与其它模式组比较,其HBV DNA含量显著增高（P＜0．01）;定性检测HBV DNA阳性组与HBV DNA阴性组比较抗－HBs值,前者抗－HBs值显著降低（P＜0．05）;抗－HBs阳性不同血清学模式病人生化指标比较无显著性差异（P＞0．05）;抗－HBs阳性不同血清学模式病人比较其肝炎临床类型的构成有非常显著性差异（P＜0．005）：即抗－HBs、抗－HBe、抗－HBc阳性组主要表现为急性肝炎,HBsAg、抗－HBS、HBeAg阳性组与HBsAg、抗－HBs阳性组主要表现为慢性肝炎。结论：抗－HBs阳性时HBV处于复制水平,但并不标志HBV复制的停止,仅预示病人感染相和恢复相的动态消长过程。如抗－HBs水平不断提高,则感染相向稳定的恢复相发展。同时从肝功能损伤的程度及肝炎临床类型分析,提示抗－HBs引发的免疫效应最终使部分病人由感染相进入恢复相。     

Genome‐free hepatitis B virion levels in patient sera as a potential marker to monitor response to antiviral therapy

Complete virions of hepatitis B virus (HBV) contain a DNA genome that is enclosed in a capsid composed of the HBV core antigen (HBcAg), which is in turn surrounded by a lipid envelope studded with viral surface antigens (HBsAg). In addition, HBV‐infected cells release subviral particles composed of HBsAg only (HBsAg ‘spheres’ and ‘filaments’) or HBsAg enveloping HBcAg but devoid of viral DNA (‘empty virions’). The hepatitis B e antigen (HBeAg), a soluble antigen related to HBcAg, is also secreted in some HBV‐infected patients. The goals of this study were to explore the levels of empty virions in HBV‐infected patients before and during therapy with the nucleotide analog tenofovir disoproxil fumarate (TDF) that inhibits HBV DNA synthesis and the relationships of empty virions to complete virions, HBsAg and HBeAg. HBV DNA, HBcAg and HBsAg levels were determined in serum samples from 21 patients chronically infected with HBV and enrolled in clinical TDF studies. Serum levels of empty virions were found to exceed levels of DNA‐containing virions, often by ≥100‐fold. Levels of both empty and complete virions varied and were related to the HBeAg status. When HBV DNA replication was suppressed by TDF, empty virion levels remained unchanged in most but were decreased (to the limit of detection) in some patients who also experienced significant decrease or loss of serum HBsAg. In conclusion, empty virions are present in the serum of chronic hepatitis B patients at high levels and may be useful in monitoring response to antiviral therapy.     

慢性乙型肝炎患者血清HBV DNA、HBeAg与肝组织HBcAg及炎症分级的关系

目的 探讨慢性乙型肝炎（CHB）患者血清HBV DNA、HBeAg与肝组织HBcAg及炎症分级的关系.方法 回顾性分析250例CHB肝穿刺患者,按血清HBV DNA水平,分为A组（＜3 log10 IU/ml）45例,B组（3～6 log10 IU/ml）138例,C组（＞6 log10 IU/ml）67例.按HBeAg阴阳性不同分为阳性组142例,阴性组108例.分别与肝组织中HBcAg水平、肝组织炎症分级进行比较,分析彼此的相关性,率的比较用卡方检验及确切概率法,相关性分析采用直线相关分析.结果 血清HBV DNA不同水平与肝组织HBcAg免疫组化比较差异有统计学意义（χ2=11.1,P=0.05）,两者之间呈正相关（r=0.75,P=0.001）;与肝组织炎症分级（G）比较差异无统计学意义（χ2=13.3,P=0.075）,两者之间也无相关性（r=0.04,P=0.325）.HBeAg阳性和阴性分组与肝组织中HBcAg水平比较差异有统计学意义（χ2=6.64,P=0.01）,两者之间呈正相关（r=0.56,P=0.001）;与肝组织炎症分级（G）比较差异无统计学意义（χ2=8.43,P=0 065）,两者之间也无相关性（r=0.06,P=0.415）.结论 CHB患者肝组织HBcAg表达更能反映出肝内HBV复制状态,患者血清中测不出病毒标志物时,可以考虑肝穿刺以观察肝组织中HBcAg表达来判断HBV复制状态具有重要意义.     

Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg‐negative and anti‐HBc antibodies‐positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer

Summary. We studied clinical outcome and clinico‐virological factors associated with hepatitis B virus reactivation (HBV‐R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)‐negative/anti‐hepatitis B core antibodies (anti‐HBcAb)‐positive patients. Between 11/2003 and 12/2005, HBV‐R occurred in 7/84 HBsAg‐negative/anti‐HBcAb‐positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV‐R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV‐R involved non‐A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV‐R is a concern in HBsAg‐negative/anti‐HBcAb‐positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti‐HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV‐R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies.