树突状细胞疫苗的制备及治疗慢性乙型肝炎的疗效观察

目的　探讨自体乙肝疫苗致敏的树突状细胞 (DC)的制备方法及其治疗慢性乙型肝炎 (CHB)的疗效。方法　取 CHB患者外周血 2 0 ml分离单个核细胞 ,加入重组人粒细胞—巨噬细胞集落刺激因子 (r GM- CSF)和白细胞介素 4 (IL- 4 )进行 DC体外扩增 ,于培养第 5天加入 5 0 μg/ m l乙型肝炎疫苗 ,7天收获细胞。 34例 CHB患者根据年龄和发病时间分为治疗 1(年龄 11～ 2 0岁 ,发病时间 0 .5～ 8.5年 )、2 (年龄 2 1～ 2 8岁 ,发病时间 3.5～ 18年 )、3(年龄 32～ 6 0岁 ,发病时间 10～ 4 2 .5年 )组 ,皮内回输 DC;对照组 CHB患者 (均为自愿停药者 ,2 0例 )注射等量生理盐水 ,均每周 1次 ,连续 8次。于回输 DC后 2周检测患者血清 HBV- DNA含量。结果　培养后可得到形态及功能典型的 DC,治疗 1、2、3组患者回输 DC后血清 HBV- DNA含量拷贝数均较对照组显著降低 (P<0 .0 1) ,总应答率 5 8.8% (2 0 / 34) ,对照组输注前后无明显变化 (P>0 .0 5 ) ;治疗 1组与 3组相比 HBV- DNA定量拷贝数降低幅度有显著性差异 (P<0 .0 1)。结论　 DC可明显降低CHB患者血清 HBV- DNA含量 ,感染病毒时间短和 /或年龄小者降低幅度大     

慢性乙型肝炎病毒感染者外周血T细胞受体β链V区谱型差异研究

目的 探讨外周血T细胞受体（TCR）β链V区（BV）CDR3区谱型差异在慢性HBV感染者炎症发生中的作用。方法研究对象为9例慢性HBV感染无症状携带（AsC）者（AsC组）和12例活动期慢性乙型病毒性肝炎（CHB）患者（CHB组）,分别采集其外周血,肝素钠抗凝,分离单个核细胞,提取RNA并应用RT-PCR扩增TCR BV的CDR3区基因24个家族,采用免疫指纹技术进行TCR BV各家族基因扫描和谱型分析。结果 两组外周血淋巴细胞TCR BV谱型均发生不同程度单克隆性、寡克隆性及偏峰性克隆增生,CHB组发生谱型偏移的TCR BV家族个数及CDR3谱型发生单克隆性和寡克隆性偏移家 族总数均显著多于AsC组（P〈0.05）。结论 CHB患者外周血T细胞克隆性增生程度高于AsC患者,此可能与慢性HBV感染者炎症的发生机制相关。     

Identification of a hepatitis B virus S gene mutant in lamivudine-treated patients experiencing HBsAg seroclearance

BACKGROUND & AIMS: Seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is a rare event in chronic hepatitis B patients receiving lamivudine therapy. It is generally believed to be a benevolent sign, implicating clearance of viremia. The aim of this study is to examine the authenticity of this dogma. METHODS: In a 5-year period, 11 patients treated with lamivudine experienced seroclearance of HBsAg. The clinical data were examined. The HBV S gene sequences derived from the patient's serum samples before and after seroclearance of HBsAg were analyzed. RESULTS: Serum HBV-DNA could be detected by nested polymerase chain reaction (PCR) in all 11 patients, by 1-step PCR in 8, and by Cobas Amplicor HBV-DNA test (>200 copies/mL) in 5. A mutation hot spot, P120A in the S gene, was identified in 6 of the 11 patients. Site-directed mutagenesis experiments indicated that the Ausria-II RIA test failed to detect this mutant. Decreased sensitivity of detection was also observed when other monoclonal antibodies were applied. CONCLUSIONS: Seroclearance of HBsAg during lamivudine therapy may not indicate viral clearance. Specifically, it may be caused by a point mutation in the S gene, which results in detection failure. In such patients, further verification and follow-up using a sensitive HBV-DNA test are advised.     

Epstein-Barr virus is related with 5-aminosalicylic acid,tonsillectomy, and CD19+ cells in Crohn’s disease

AIM: To study anti-Epstein-Barr virus (EBV) IgG antibodies in Crohn´s disease in relation to treatment, immune cells, and prior tonsillectomy/appendectomy.METHODS: This study included 36 CD patients and 36 healthy individuals (controls), and evaluated different clinical scenarios (new patient, remission and active disease), previous mucosa-associated lymphoid tissue removal (tonsillectomy and appendectomy) and therapeutic regimens (5-aminosalicylic acid, azathioprine, anti-tumor necrosis factor, antibiotics, and corticosteroids). T and B cells subsets in peripheral blood were analyzed by flow cytometry (markers included: CD45, CD4, CD8, CD3, CD19, CD56, CD2, CD3, TCRαβ and TCRγδ) to relate with the levels of anti-EBV IgG antibodies, determined by enzyme-linked immunosorbent assay.RESULTS: The lowest anti-EBV IgG levels were observed in the group of patients that were not in a specific treatment (95.4 ± 53.9 U/mL vs 131.5 ± 46.2 U/mL, P = 0.038). The patients that were treated with 5-aminosalicylic acid showed the highest anti-EBV IgG values (144.3 U/mL vs 102.6 U/mL, P = 0.045). CD19⁺ cells had the largest decrease in the group of CD patients that received treatment (138.6 vs 223.9, P = 0.022). The analysis of anti-EBV IgG with respect to the presence or absence of tonsillectomy showed the highest values in the tonsillectomy group of CD patients (169.2 ± 20.7 U/mL vs 106.1 ± 50.3 U/mL, P = 0.002). However, in the group of healthy controls, no differences were seen between those who had been tonsillectomized and subjects who had not been operated on (134.0 ± 52.5 U/mL vs 127.7 ± 48.1 U/mL, P = 0.523).CONCLUSION: High anti-EBV IgG levels in CD are associated with 5-aminosalicylic acid treatment, tonsillectomy, and decrease of CD19⁺ cells.     

Metabolic stress is a barrier to Epstein–Barr virus-mediated B-cell immortalization

Epstein–Barr virus (EBV) is an oncogenic herpesvirus that has been causally linked to the development of B-cell and epithelial malignancies. Early after infection, EBV induces a transient period of hyperproliferation that is suppressed by the activation of the DNA damage response and a G1/S-phase growth arrest. This growth arrest prevents long-term outgrowth of the majority of infected cells. We developed a method to isolate and characterize infected cells that arrest after this early burst of proliferation and integrated gene expression and metabolic profiling to gain a better understanding of the pathways that attenuate immortalization. We found that the arrested cells have a reduced level of mitochondrial respiration and a decrease in the expression of genes involved in the TCA cycle and oxidative phosphorylation. Indeed, the growth arrest in early infected cells could be rescued by supplementing the TCA cycle. Arrested cells were characterized by an increase in the expression of p53 pathway gene targets, including sestrins leading to activation of AMPK, a reduction in mTOR signaling, and, consequently, elevated autophagy that was important for cell survival. Autophagy was also critical to maintain early hyperproliferation during metabolic stress. Finally, in assessing the metabolic changes from early infection to long-term outgrowth, we found concomitant increases in glucose import and surface glucose transporter 1 (GLUT1) levels, leading to elevated glycolysis, oxidative phosphorylation, and suppression of basal autophagy. Our study demonstrates that oncogene-induced senescence triggered by a combination of metabolic and genotoxic stress acts as an intrinsic barrier to EBV-mediated transformation.Epstein–Barr virus (EBV) is a gamma herpesvirus that establishes a lifelong, latent infection in >90% of adults worldwide. EBV is associated with a number of malignancies, including African endemic Burkitt’s lymphoma, posttransplant lymphoproliferative disease, nasopharyngeal carcinoma (NPC), and HIV-associated lymphomas (1). These malignancies primarily develop in immunocompromised patients, pointing to the critical role that the immune system plays in controlling infection. However, it has recently become appreciated that additional intrinsic responses limit the ability of EBV to transform cells.In vitro stimulation of B cells either through EBV infection or mitogen treatment results in a transient period of hyperproliferation reminiscent of a germinal center reaction. EBV elicits entry into the cell cycle through the EBV latency proteins, EBNA2 and EBNA-LP, which up-regulate the expression of progrowth genes (2–4). This period of rapid proliferation leads to the activation of the DNA damage response (DDR), which can signal through p53 to induce either apoptosis or senescence (5). In contrast to mitogen-stimulated cells, EBV-infected cells are able to escape apoptosis and, instead, a subset undergo a G1/S-phase growth arrest (6). The specific cellular pathways that contribute to this growth arrest are poorly understood.Oncogene-induced senescence (OIS) is a premature form of senescence in which cells undergo an irreversible growth arrest after chronic oncogene expression or the inactivation of tumor suppressors (7, 8). Current models suggest that the onset of OIS is a consequence of a persistent DDR resulting from replicative stress induced during oncogene-driven hyperproliferation (9–11). It is now appreciated that OIS plays an important role in suppressing tumorigenesis in a wide range of cell types (7). Additionally, studies suggest that OIS can suppress proliferation driven by the overexpression of viral proteins or after oncogenic virus infection (12, 13).Increasing evidence suggests that there is a link between senescence and macroautophagy (hereafter referred to as autophagy) (7). Autophagy is a catabolic process in which organelles or proteins are targeted for lysosomal degradation and recycling (14, 15). Studies have demonstrated that autophagy promotes cell-cycle arrest and the production of senescence-associated interleukins (16). However, autophagy has also been linked to the progression of tumorigenesis by providing metabolic intermediates to fuel proliferation (14). Oncogene activation leads to a substantial increase in the need for ATP, biosynthetic intermediates, and reducing equivalents to maintain proliferation, thereby creating metabolic stress (17). Cancer cells have been shown to mitigate this stress by up-regulating the basal level of autophagy and by transitioning their metabolic profile from oxidative phosphorylation (OXPHOS) toward aerobic glycolysis, also known as the Warburg effect (18, 19).The essential role of metabolism in driving virus replication has been hinted at since the 1950s and is now becoming fully appreciated with the advent of new technologies (20). It is now appreciated that many eukaryotic viruses alter host metabolism to provide the energetic and biosynthetic resources necessary to drive virus replication and virion production. Less intuitive is the observation that viruses also alter host cellular metabolism during latent infection despite the lack of need for biosynthetic intermediates to produce viral progeny. Kaposi’s sarcoma-associated herpesvirus (KSHV) induces a Warburg effect during latent infection of endothelial cells, which is necessary for the survival of infected cells (21). A detailed metabolomics study of cells latently infected with KSHV further confirmed the increased production of glycolytic metabolites and also found an up-regulation of long-chain fatty acids (21). Additionally, glycolysis and fatty acid synthesis were found to be up-regulated in KSHV-associated primary effusion lymphoma compared with uninfected B cells (22). EBV latency is also associated with an altered metabolic state. EBV-infected nasopharyngeal carcinoma (NPC) cells exhibit high levels of glycolysis, an effect that can be recapitulated by the expression of EBV latency protein, latent infection membrane protein 1 (LMP1), alone (23). This increased level of glycolysis could be attributed to the increased surface expression of GLUT1 that was shown to be associated with LMP1-mediated NF-κB signaling in B cells (24). However, LMP1 expression is low during EBV-induced B-cell hyperproliferation—a period in which the cell should have the greatest need for increased metabolic flux.In the present study, we have developed a method to identify and isolate EBV-infected primary human B cells that initially undergo a period of hyperproliferation and then arrest. We have used this approach to define the metabolic demands of hyperproliferation that drives the majority of EBV-infected cells into permanent growth arrest.     

A case-control study of response to lamivudine therapy for 2 years in Japanese and Chinese patients chronically infected with hepatitis B virus of genotypes Bj, Ba and C.

BACKGROUND/AIMS: In eastern Asian countries, hepatitis B virus (HBV) genotype Ba (HBV/Ba), HBV/Bj and HBV/C are prevalent. The aim was to investigate the response or resistance to lamivudine therapy among patients with different HBV genotypes. METHODS: Of 67 Japanese and Chinese patients with chronic hepatitis B, 18 patients with HBV/Bj, 15 with HBV/Ba and 34 with HBV/C were selected for a case-control study matched according to gender and age. All the patients were treated with lamivudine for 2 years and evaluated the response or emergence of the YMDD mutation at year 2 during the treatment. HBV genotypes were detected by the restriction fragment length polymorphism. The YMDD mutation was detected by the direct sequencing after amplification by PCR. RESULTS: At year 2 during therapy, 44.8% of the patients showed normalization of ALT and undetectable HBV DNA (favorable response), 35.8% developed the YMDD mutation. There was no significant difference of response to the therapy among the three genotype groups. The emergence of the YMDD mutation was associated with HBV/C. By the multiple logistic regression analysis, however, the significant factor of a favorable response was a higher pretreatment ALT level and negative HBeAg status and the significant factor of the emergence of the YMDD mutation was HBV/C. CONCLUSIONS: Higher pretreatment ALT level, HBeAg status or HBV genotype may affect the response or resistance to lamivudine therapy.     

Effect of α-interferon on hepatitis B virus-specific cytotoxic T cells

Abstract To study the mechanism of the effects of α-interferon (α-IFN) on chronic hepatitis B, we examined its effect on hepatitis B virus (HBV)-specific cytotoxic T cells (CTL). Using two different HBV-DNA transfected human myeloma cell lines, one expressing hepatitis B core antigen (HBcAg; C4) and the other expressing hepatitis B surface antigen (HBsAg; S6) as targets in cytotoxic tests in vitro , peripheral blood mononuclear cells obtained from chronic hepatitis B patients who were treated with α-IFN were examined for their cytotoxic activity against these transfectants. During the treatment with α-IFN, in association with a decline of serum alanine amino transferase levels, CTL activities were significantly reduced. An inhibition study in vitro revealed that α-IFN did not directly inhibit these CTL activities, indicating that α-IFN may inhibit the induction of CTL, and thereby may be related to the reduction of hepatocyte injury.     

美国2006年慢性乙型肝炎病毒感染处理治疗规范简介

2004年Keeffe等在“临床胃肠病和肝病学”杂志上发表“美国慢性乙型肝炎病毒感染处理治疗规范”。近2年来，由于美国食品药品监督管理局（FDA）先后批准恩替卡韦和聚乙二醇化干扰素（PegIFN）α--2a用于慢性乙型肝炎治疗，并对慢性乙型肝炎的自然史有了新的研究结果，因此，最近Keeffe等美国肝病专家对该《规范》进行了修订，并发表于2006年7月“临床胃肠病和肝病学”杂志。     

抑制消减杂交法筛选无症状乙型肝炎病毒携带者差异表达基因

乙型肝炎病毒（HBV）携带者中,大多数是婴幼儿期感染,往往终生携带HBV,但正常成人初次感染后大多能清除病毒.除病毒因素外,主要是机体的免疫因素决定感染结局[1].机体对HBV的免疫应答受许多基因的调节,我们推测正是由于在正常人和HBV携带者之间存在的免疫相关基因表达的差异才导致了不同的感染结局.本研究旨在探讨HBV携带者与正常人外周血单个核细胞（PBMC）差异表达的基因,有助于阐明HBV携带发生发展机制及设计新的治疗靶标.     

含乙型肝炎病毒C基因的重组腺相关病毒对树突状细胞的作用

目的 研究腺相关病毒(AAV)为载体的含有乙型肝炎病毒(HBV)C基因重组病毒(rAAV-HBV-C)感染树突状细胞(DC)的效率及对DC生长和成熟的影响。 方法 从正常人外周血中分离单个核细胞收取单核细胞进行体外培养,分别用rAAV-HBV-C和293细胞裂解物感染刺激单核细胞,感染后的单核细胞在粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素4(IL-4)和肿瘤坏死因子α(TNF α)存在的条件下继续培养获得成熟的DC。用逆转录聚合酶链反应及流式细胞仪细胞内染色检测目的基因(HBV-C)的转录及表达;通过观察不同时间DC的形态及检测收获DC时其表面分化抗原(CD)的表达来评价DC的生长和成熟状态。 结果 rAAV-HBV-c感染后的DC可转录HBV-C基因并表达HBV-C抗原,病毒感染组与对照组收获的DC在细胞形态与CD表达方面差异无统计学意义。 结论 rAAV-HBV-C可有效感染DC,感染的病毒对DC的生长及成熟没有显著影响。     

重型乙型肝炎患者血清乙型肝炎病毒全基因克隆及测序

目的建立重型乙型肝炎患者血清乙型肝炎病毒（HBV）DNA克隆并测序，从全基因水平分析HBV基因变异与重型乙型肝炎发病的关系。方法10例重型乙型肝炎患者血清提取HBV DNA，聚合酶链反应（PCR）扩增HBV全基因。PCR产物构建到PUCm-T载体上，转化至大肠杆菌感受态DH-5α细胞，经酶切鉴定，获得含3．2Kb HBVDNA的重组克隆菌，全基因测序，分析各读码框核苷酸和氨基酸变化。结果4例成功构建HBV DNA克隆，并完成全基因测序。其中3例在前C区发生G1896A变异，产生一个终止密码子，导致HBeAg缺失；1例在C启动子区1762、1764双位点出现突变；有多处点突变及缺失变异分布于PreS2区及C区已知细胞毒T淋巴细胞、B淋巴细胞和T淋巴细胞的细胞表位。结论该法可用于临床研究HBV病毒基因结构与重型乙型肝炎发病的关系，并为进一步研究其HBV基因功能奠定基础。     

HBVM阳性肺结核患者HBVDNA检测的临床意义

目的探讨HBVDNA（乙型肝炎病毒DNA）、HBVM（乙型肝炎病毒标志物）阳性肺结核患者抗结核治疗时对肝损害的影响。方法肺结核患者HBVM阳性且HBVDNA阳性为观察组A，HB．VM阳性、HBVDNA阴性者为观察组B，HBVM阴性为对照组C，观察各组抗结核药物肝损害发生率、停药率及A组HBVDNA水平与肝损害发生率、停药率有无相关。结果各组肝损害发生率两两比较均有显著性差异（P〈0．01）；A组停药率与其他两组均有显著性差异（P〈0．01），B组与C组无显著性差异（P〉0．05）；A组HBVDNA水平与肝损害发生率、停药率无相关（P〉0．05）。结论HBVM阳性尤其HBVDNA阳性肺结核化疗应重视，HBVDNA阴性者可短程化疗，HBVDNA阳性者都应慎行短程化疗。     

A novel immunocompetent rat model of HCV infection and hepatitis

BACKGROUND & AIMS: Hepatitis C virus (HCV) infects millions of people worldwide. Therapy is limited, and treatment does not produce a sustained response in the majority of patients. Development of new agents has been hampered by the lack of a convenient animal model. The aim of this study was to determine whether an immunocompetent rat, tolerized and transplanted with a human hepatoma cell line (Huh 7 cells), could be used to sustain an HCV infection. METHODS: Fetal rats were tolerized in utero with 10(5) Huh 7 cells. One day after birth, rats were transplanted with 5 x 10(6) Huh 7 cells and, a week later, inoculated with HCV, genotype 1. RESULTS: In tolerized, transplanted, and HCV-infected rats, Huh 7 cells were found in the liver, and HCV viral replication was detected by the presence of negative strand HCV RNA. HCV levels in serum were measured at 11,000 copies/mL at week 4, peaked at 22,500 copies/mL by week 12. In tolerized, transplanted, inoculated rats, but not controls, serum alanine aminotransferase (ALT) values increased to 60 IU/L by week 4 and reached a peak of approximately 120 IU/L by week 13. Histology showed foci of mononuclear infiltrates in portal and central regions. CONCLUSIONS: HCV-inoculated immunocompetent rats tolerized and transplanted with Huh 7 cells support HCV gene expression, viral replication, and develop biochemical and histologic evidence of hepatitis.     

乙型肝炎病毒嗜肝结合位点与受体的研究进展

众多学者对HBV嗜肝性机制得出共识:HBV膜蛋白直接与肝细胞膜上相应的受体结合,继而膜融合,通过胞饮作用内吞入胞;或者HBV与细胞外液中某一中介分子结合形成复合体,再与肝细胞膜上其相应的受体结合入胞.但目前仍不能确定膜受体及中介分子是什么.现就近年来HBV嗜肝机制研究综述如下.     

慢性乙型肝炎患者树突状细胞Toll样受体3触发后Ⅰ型干扰素的表达

目的 了解慢性乙型肝炎(CHB)患者外周血单个核细胞来源的树突状细胞Toll样受体3(TLR3)触发后Ⅰ型IFN表达情况.方法 选取CHB患者26例,健康对照者18例,抽取外周血用免疫磁珠细胞分选法获得纯化的单核细胞(同时留取血浆),体外培养诱导为未成熟的树突状细胞,给予聚肌胞苷酸(Poly Ⅰ:C)刺激,在刺激0、24 h收集细胞培养上清液,用ELISA法测定血浆及细胞培养上清液中Ⅰ型IFN(IFN-α,IFN-β)表达水平.均数间两两比较采用t检验.结果 在血浆中,两组Ⅰ型IFN表达水平的差异无统计学意义.刺激前(0 h),CHB组单个核细胞来源的树突状细胞表达的IFN-α、IFN-β分别为(80.00±16.15)ng/L和(36.39±13.90)ng/L,对照组分别为(76.76±15.90)ng/L和(37.14±13.68)ng/L,差异均无统计学意义(t=1.651,t=0.178;均P＞0.05).两组刺激后24 h的IFN-α表达水平均比刺激前(0 h)升高,但差异无统计学意义(t=1.534,t=1.243;均P＞0.05).刺激后24 h,对照组IFN-β水平为(54.57±16.80)ng/L,显著高于刺激前(0 h)的(37.14±13.68)ng/L(t=4.061,P＜0.05);但在CHB组,两者的差异无统计学意义(t=1.796,P＞0.05).刺激后24 h,两组的IFN-α表达水平差异无统计学意义(t=0.792,P＞0.05),而IFN-β水平在对照组为(54.57±16.80)ng/L,显著高于CHB组的(41.64±12.57)ng/L(t=2.921,P＜0.05).结论 CHB患者单个核细胞来源的树突状细胞存在功能障碍,不能正常表达Ⅰ型IFN.TLR3触发后单个核细胞来源的树突状细胞表达的Ⅰ型IFN以IFN-β为主.     

Construction of a replication-competent hepatitis B virus vector carrying secreted luciferase transgene and establishment of new hepatitis B virus replication and expression cell lines

BACKGROUND Previously, we have successfully constructed replication-competent hepatitis B virus(HBV) vectors by uncoupling the P open reading frame(ORF) from the preC/C ORF to carefully design the transgene insertion site to overcome the compact organization of the HBV genome and maintain HBV replication competence. Consequently, the replication-competent HBV vectors carrying foreign genes, including pCH-BsdR, carrying blasticidin resistance gene(399 bp),and pCH-hrGFP, carrying humanized renilla green fluorescent protein gene(720 bp), were successfully obtained. However, the replication efficiency of the former is higher but it is tedious to use, while that of the latter is poor and cannot be quantified. Hence, we need to search for a new reporter gene that is convenient and quantifiable for further research.AIM To establish a helpful tool for intracellular HBV replication and anti-viral drugs screening studies.METHODS We utilized the replication-competent HBV viral vectors constructed by our laboratory, combined with the secreted luciferase reporter gene, to construct replication-competent HBV vectors expressing the reporter gene secretory Nanoluc Luciferase(SecNluc). HepG2.TA2-7 cells were transfected with this vector to obtain cell lines with stably secreted HBV particles carrying sec Nluc reporter gene.RESULTS The replication-competent HBV vector carrying the SecNluc reporter gene p CHs NLuc could produce all major viral RNAs and a full set of envelope proteins and achieve high-level secreted luciferase expression. HBV replication intermediates could be produced from this vector. Via transfection with pTRE-sNLuc and selection by hygromycin, we obtained isolated cell clones, named HBV-NLuc-35 cells, which could secrete sec NLuc recombinant viruses, and were sensitive to existing anti-HBV drugs. Using differentiated Hepa RG cells, it was verified that recombinant HBV possessed infectivity.CONCLUSION Our research demonstrated that a replication-competent HBV vector carrying a secreted luciferase transgene possesses replication and expression ability, and the established HBV replication and expression cell lines could stably secrete viral particles carrying sec Nluc reporter gene. More importantly, the cell line and the secreted recombinant viral particles could be used to trace HBV replication or infection.     

HTLV-1 associated myelopathy in an HTLV-1 and HBV double carrier family: Report of a case and the mode of vertical transmission of both viruses

Osame et al. first described human T cell lymphotropic virus type 1 (HTLV-1) associated myelopathy (HAM) as a new clinical entity in 1986. A 23 year old female diagnosed as having HAM whose family had a high frequency of double virus infection with HTLV-1 and hepatitis B virus (HBV) gave reason to suspect mother-to-child transmission of both viruses. No clear coincidence in the mode of transmission of HTLV-1 and HBV was found. It is presumed that the mechanism of infection with HTLV-1 and HBV differ slightly.     

对1例隐匿性慢性乙型肝炎的病例分析

1病历资料患者男,38岁,司机,因"间断性右季肋区不适2年,加重2月余"就诊。2年前患者无明显诱因自觉肝区不适,在我院就诊时查乙型肝炎系列示:HBsAg阴性、抗-HBs阳性、HBeAg阴性、抗-HBe阳性、抗-HBc阳性,当时未行进一步诊治。2011年2月初患者无明显诱因,再次出现右季肋区不适,查乙型肝炎系列示:HBsAg阴性、抗-HBs阳性、HBeAg阴性、抗-HBe阳性、抗-HBc阳性,甲、丙、戊、丁型肝炎抗体、     

e抗原阴性慢性乙型肝炎患者血清表面抗原大蛋白水平与乙型肝炎病毒DNA之间的关系

我国约1／3的慢性乙型肝炎患者乙型肝炎e抗原（HBeAg）阴性，但仍然伴有高水平的乙型肝炎病毒（HBV）复制。在不能进行HBV DNA检测的单位，对这些患者HBV复制程度的判定难以进行。现探讨HBeAg阴性慢性乙型肝炎患者血清中乙型肝炎病毒表面抗原大蛋白（LHBs）与HBV DNA的关系，试图明确LHBs是否可以用作HBeAg阴性乙型肝炎患者病毒复制程度的判定指标。