Safety of hepatitis B virus core antibody-positive grafts in liver transplantation: A single-center experience in China

BACKGROUND Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive(HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of China's Mainland. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal.AIM To evaluate the safety of using hepatitis B virus(HBV) core antibody-positive donors for liver transplantation in Chinese patients.METHODS We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study.RESULTS In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative(HBcAb-) liver grafts. The 1-, 3-and 5-year survival rates in patients and grafts between the two groups were similar(patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3-and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcA b+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive(HBsAg+) and HBsA g negative(HBsAg-) patients.Newly diagnosed HBV infection had a relatively higher incidence in HBsAg-patients with HBcAb+ liver grafts(13.23%), in which HBV naive recipients suffered most(31.82%), although this difference did not affect patient and graft survival(P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody(anti-HBs) titer(more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks. CONCLUSION HBcA b+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.

Positive Rate of Different Hepatitis B Virus Serological Markers in Peking Union Medical College Hospital,a General Tertiary Hospital in Beijing

Objectives To investigate the positive rate of different hepatitis B virus （HBV） serological markers, and the demographic factors related to HBV infection. Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen （HBsAg）, HBV surface antibody （HBsAb）, hepatitis B e antigen （HBeAg）, hepatitis B e antibody （HBeAb）, HBV core antibody （HBcAb）, and HBV-DNA from July 2008 to July 2009 in Peking Union Medical College Hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and department, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed. Results Among 27 409 samples included, 2681 （9.8%） were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2%, 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2%, 5.8%, and 4.7%, respectively. The positive rate of HBsAg of males （13.3%） was higher than that of females （7.3%, P=0.000）. Among the 2681 HBsAg （＋） patients, 1230 （45.9%） had HBV-DNA test, of whom 564 （45.9%） were positive. Patients with HBsAg （＋）, HBeAg （＋）, and HBcAg （＋） result usually had high positive rate of HBV-DNA results （71.8%, P=0.000）. Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 20-29, males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.

Hepatitis B virus reactivation in hepatitis B virus surface antigen negative patients receiving immunosuppression: A hidden threat

AIM: To present the characteristics and the course of a series of anti- hepatitis B virus core antibody (HBc) antibody positive patients, who experienced hepatitis B virus (HBV) reactivation after immunosuppression. METHODS: We retrospectively evaluated in our tertiary centers the medical records of hepatitis B virus surface antigen (HBsAg) negative patients who suffered from HBV reactivation after chemotherapy or immunosuppression during a 3-year period (2009-2011). Accordingly, the clinical, laboratory and virological characteristics of 10 anti-HBc (+) anti-HBs (-)/HBsAg (-) and 4 anti-HBc (+)/antiHBs (+)/HBsAg (-) patients, who developed HBV reactivation after the initiation of chemotherapy or immunosuppressive treatment were analyzed. Quantitative determination of HBV DNA during reactivation was performed in all cases by a quantitative real time polymerase chain reaction kit (COBAS Taqman HBV Test; cut-off of detection: 6 IU/mL). RESULTS: Twelve out of 14 patients were males; median age 74.5 years. In 71.4% of them the primary diagnosis was hematologic malignancy; 78.6% had received rituximab (R) as part of the immunosuppressive regimen. The median time from last chemotherapy schedule till HBV reactivation for 10 out of 11 patients who received R was 3 (range 2-17) mo. Three patients (21.4%) deteriorated, manifesting ascites and hepatic encephalopathy and 2 (14.3%) of them died due to liver failure. CONCLUSION: HBsAg-negative anti-HBc antibody positive patients can develop HBV reactivation even 2 years after stopping immunosuppression, whereas prompt antiviral treatment on diagnosis of reactivation can be lifesaving.

Establishment of transgenic mouse harboring hepatitis B virus (adr subtype) genomes

INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).

“Anti-HBc alone” in human immunodefi ciency virus-positive and immuno-suppressed lymphoma patients

Hepatitis B virus (HBV) infection is endemic in various parts of the world. A proportion of patients have resolved prior exposure to HBV, as evidenced by the clearance of circulating hepatitis B surface antigen and the appearance of antibody to hepatitis B core antigen (anti-HBc), which could produce protective antibody to hepatitis B surface antigen (anti-HBs). With time, anti-HBs in some patients may become negative. Such patients are described as having occult HBV infection or "anti-HBc alone". In the context of immunodef icient patients, such as HIV patients or lymphoma patients undergoing immunosuppressive immunotherapy, the lack of protective anti-HBs may increase the risk of hepatitis B reactivation. Serum HBV DNA testing may be necessary in "anti-HBc alone" patients, to detect patients at a high risk of developing HBV infection allowing appropriate prophylactic management.

宁夏地区孕产妇HBV检测及感染状况调查研究

目的 了解2015—2021年宁夏地区孕产妇乙型肝炎病毒(HBV)检测及感染情况。方法 收集2015—2021年宁夏各助产机构发现并上报的感染HBV的孕产妇信息,通过预防艾滋病、梅毒和乙型肝炎母婴传播信息管理系统收集相关数据,并分析宁夏地区孕产妇HBV检测率、检测时期和HBV表面抗原(HBsAg)阳性率及其分布特征。结果 2015—2021年宁夏孕产妇HBV检测率99.95%,孕期检测率从69.11%上升至98.13%。累计648 360例孕产妇接受了HBV检测,报告HBsAg阳性孕产妇24 600例,HBsAg阳性率3.79%。24 600例HBsAg阳性孕产妇中,4 847例(19.70%)为仅产时接受检测。孕产妇孕期HBsAg阳性率呈逐年上升趋势,仅产时HBsAg阳性率呈逐年下降趋势,且2015—2019年孕产妇仅产时HBsAg阳性率均高于同期孕产妇孕期HBsAg阳性率。此外,2021年报告2 435例HBV感染孕产妇感染模式,14~<25岁组以模式1感染为主,25~<35岁组、35~<47岁组均以模式2感染为主。结论 2015—2021年宁夏地区孕产妇HBV检测率保持较高水平,孕期检测率显著上升,但仍存在一定比例的产时检测,需进一步采取措施促进孕产妇孕期尽早接受HBV检测,同时加强HBV感染孕产妇疾病监测管理。

Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient:A case report

BACKGROUND Hepatocellular carcinoma(HCC)may be caused by hepatitis B virus(HBV)infection.Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen(HBsAg)level and increased anti-HBsAg antibody titer.Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC deve-lopment.Here,we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level(over 2000 ng/mL)of serum alpha-fetoprotein.Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly.Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen(anti-HBcAg antibodies),an extremely high titer(1000 mIU/mL)of hepatitis B surface antibodies(anti-HBsAg antibodies,anti-HBs)and absence of detectible HBsAg.Medical records indicated that the patient had reported no history of HBV vaccination,infection or hepatitis.Therefore,to rule out latent HBV infection in this patient,a serum sample was collected then tested to detect HBV DNA,yielding a positive result.Based on the aforementioned information,the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.

Evaluate the prevalence and trend of hepatitis B and hepatitis C in Nahavand: west of Iran, 2013–2017

Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection with two types of hepatitis.Infection with these viruses is a global health problem and continuous efforts are in place to identify infected people through targeted screening,preventing new infections through vaccination,monitoring and treating people at risk for complications of all types of hepatitis.The aim of this study was to determine the evaluate the prevalence and trends of hepatitis B and C infection in the Nahavand city during 5 consecutive years(2013–2017).The total number of patients with hepatitis B and C was 141 persons from March 2013 to March 2017,of these,101 had hepatitis B,and 40 had hepatitis C.The prevalence of hepatitis B and C was higher in men than women.The percentage frequency hepatitis B in the city in the last five years was 0.05 percent.11 cases(10.89%)pregnant women and Six cases(5.9%)receiving blood(blood transfusions)in Hepatitis B was observed.the prevalence of hepatitis C was 0.2%at the end of 2017.The study on the cause of hepatitis C in Nahavand has shown that 21(52.5%)of the total of 40 people were infected with addiction.The interesting point in this report is that according to reports from viral hepatitis testing questionnaires,24 of 101 people with type B hepatitis have 23.7%of people with a history of complete vaccination of hepatitis B and one person(0.9%)had incomplete vaccination.A significant relationship was found between the level of education and the prevalence of hepatitis(P=0.005).

HBsAg(+)供体肾移植HBsAg(-)受体的相关研究进展

肾移植已成为肾病终末期患者的首选治疗方法,其进一步的推广与发展仍面临部分问题,供体不足仍是限制肾移植手术开展的重要因素之一。乙肝感染者的肾脏是重要的供体来源,其作为血液传播性疾病,应用乙肝表面抗原阳性供体肾脏可能造成乙肝病毒在供受体之间传播,在部分实验中观察到受体乙肝表面抗原转阳等情况,导致受体术后生存率的减少与生活质量的降低。因此需要在不同供受体情况下选择应用相应个体化的预防与治疗手段,减少病毒传播的风险,以及术后随访的过程中通过对相应指标的监测与随访及时发现潜在的病毒传播情况并采取相应对策,期望将不同供受体的移植情况进行系统性总结,为肾移植围手术期治疗方案提供理论与应用参考。

乙型肝炎病毒核心抗体水平与慢性乙型肝炎患者肝脏炎症、纤维化程度及抗病毒疗效关系的Meta分析

目的系统评估乙型肝炎病毒核心抗体(hepatitis B virus core antibody,HBcAb)水平与慢性乙型肝炎(chronic hepatitis B,CHB)患者肝脏炎症及纤维化程度的相关性,以及HBcAb能否作为CHB患者抗病毒疗效的预测指标。方法检索PubMed、Embase、Web of Science、The Cochrane Library、中国知网、万方、维普数据库建库至2022年10月发表的有关HBcAb的文献。使用R4.2.1软件进行Meta分析,横断面研究文献质量评价参照美国卫生保健质量和研究机构(the Agency for Healthcare Research and Quality,AHRQ)提出的文献质量评价标准,队列研究质量评价参照纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)。采用剔除异质性最大或权重最大的文献进行敏感性分析。采用漏斗图和Egger检验进行发表偏倚评估。结果纳入30篇文献进行系统评价,其中21篇文献纳入Meta分析。结果表明HBcAb水平越高,CHB患者肝脏炎症程度(Summary r=0.39,95%CI:0.30~0.48,P<0.05)和肝脏纤维化程度(Summary r=0.33,95%CI:0.22~0.43,P<0.05)均越高。ALT基本正常的CHB患者中HBcAb较低的患者发生肝脏炎症(G2~G4)的风险较高(OR=2.02,95%CI:0.64~6.38,P<0.05)。干扰素(interferon,IFN)治疗的CHB患者基线HBcAb水平越高,HBsAg阴转率越高(MD=0.34,95%CI:-0.12~0.80,P<0.05)。核苷(酸)类似物[nucleos(t)ide analogues,NAs]和IFN治疗的CHB患者基线HBcAb水平越高,HBeAg血清学转换率(MD=0.37,95%CI:0.26~0.49,P<0.05)和HBV DNA病毒学应答率(MD=0.30,95%CI:0.16~0.44,P<0.05)均越高。IFN治疗的CHB患者停药时HBcAb水平越高,临床治愈后复发率越低(MD=-0.74,95%CI:-1.00~-0.48,P<0.05)。结论HBcAb水平越高,CHB患者肝脏炎症程度及纤维化程度越高。较高的HBcAb水平可作为预测NAs或IFN抗病毒疗效的指标之一。

干扰素抗体与HBV C基因启动子变异对干扰素疗效的影响

目的 探讨HBVC基因启动子 (BCP)变异的肝炎患者干扰素抗体 (抗 IFN )的产生对干扰素疗效的影响。方法 采用错配PCR RFLP技术检测 89例慢性乙型肝炎血清中BCP变异和血清中抗 IFN的水平。结果 BCP变异率为 5 2 .8%,抗 IFN阳性率为 15 .6 %,而干扰素治疗前抗 IFN阳性与治疗后转为阳性的患者 ,其干扰素治疗的有效率差异无显著性 (P >0 .0 5 ) ,而治疗前后抗 IFN均为阴性者 ,其有效率明显优于阳性者 ,差异显著 (P <0 .0 5 )。在IFN治疗前 ,有BCP变异组抗 IFN阳性 10例 ,野生株组抗 IFN阳性 2例 ,两组相比 ,差异显著 (P <0 .0 5 )。IFN治疗后 ,变异株组出现抗 IFN阳性 4例 ,野生株组出现抗 IFN阳性 1例 ,差异无显著性 (P >0 .0 5 )。结论 抗 IFN阳性的患者 ,干扰素治疗效果差。BCP变异的患者 ,在干扰素治疗前 ,有可能促进干扰素抗体的产生 ,但在干扰素治疗后 ,则不增加抗 IFN的产生。

HBcAb阳性伴HBsAb阴性的人群HBsAg合适临界值的研究

目的:HBcAb阳性伴HBsAb阴性的人群HBsAg合适临界值的研究。方法:收集并检测HBcAb阳性伴HBsAb阴性组HBsAg阴性及HBcAb阴性伴HBsAb阴性组HBsAg阴性的样本各1 522例,比较两组HBsAg结果的差异。采用ROC曲线对ELISA定性HBsAg结果诊断HBcAb阳性伴HBsAb阴性的人群的阳性判断值的再确定,寻找更好的的诊断性能。结果:i2000SR检测HBsAg的结果具有良好的重复性,符合临床检测要求。HBcAb阴性组复检前与复检后相比明显降低,复检后HBcAb阳性组的结果相比阴性组明显降低,差异具有统计学意义(P<0.05);利用ROC曲线对HBcAb阳性伴HBsAb阴性的人群HBsAg建立合适临界值为0.415后的准确度、敏感度、特异度、阳性预测值、阴性预测值、曲线下面积、Youden指数显示具有更好的诊断性能。HBcAb阳性伴HBsAb阴性人群的HBsAg结果与HBcAb阴性伴HBsAb阴性人群HBsAg的相比明显升高,差异具有统计学意义(P<0.05)。结论:实验室建立HBcAb阳性伴HBsAb阴性人群的ELISA法定性HBsAg结果合适的的阳性判值具有更好的诊断性能。

儿童与成人慢性乙型肝炎患者乙型肝炎病毒Core基因区准种特征及正选择压力差异分析

儿童与成人慢性乙型肝炎患者的临床特征差异明显。乙型肝炎病毒(Hepatitis B virus,HBV)病毒准种特征与其致病特性紧密相连,HBV病毒Core基因区富含免疫表位,该区域的准种特征直接反映病毒变异与病毒应对宿主免疫压力间的动态过程。文章通过扩增170名儿童慢性乙型肝炎患者及121名成人慢性乙型肝炎患者病毒Core基因区,按照病毒基因型以及病毒e抗原(Hepatitis B virus e antigen,HBe Ag)状态进行分组,使用序列复杂度、多样性、非同义突变率(Non-synonymous substitution ratio,d N)、同义突变率(Synonymous substitution ratios,d S)等指标衡量不同组别之间的病毒准种特征;使用不同模型计算不同组别中受到正选择压力的位点,进一步结合HBV Core基因区免疫表位信息,进行正选择位点的定位分析。结果发现,儿童乙型肝炎病毒患者体内病毒Core基因区序列复杂性和多样性低于成人患者,且前者Core基因区正选择位点个数显著低于后者,这说明儿童慢性乙型肝炎患者体内病毒受到的选择压力低于成人患者。在儿童及成人慢性感染病人组中,HBe Ag阳性病人体内病毒受到的选择压力低于HBe Ag阴性病人。儿童及成人慢性感染患者体内病毒存在13个正选择位点,大多数正选择位点位于已知的抗原表位上。本研究从分子进化角度揭示了儿童与成人慢性乙型肝炎病例体内病毒Core基因区序列准种差异,为两类病人显著不同的临床表征提供了群体遗传学的解释。

抗鸭乙肝病毒core蛋白单克隆抗体的制备与鉴定

目的制备抗鸭乙肝病毒core蛋白的单克隆抗体并进行鉴定。方法 PCR扩增鸭乙肝病毒(DHBV)core基因片段,构建表达载体pET28a(+)/DHBV core。转化诱导表达融合蛋白,用Ni 2+亲和柱纯化目的蛋白。免疫Balb/c小鼠,取脾细胞与SP2/0骨髓瘤细胞融合,ELISA筛选,采用有限稀释法筛选单克隆杂交瘤细胞并进行细胞克隆。体内诱生法大量制备单克隆抗体,进行抗体的特异性、效价和亚型的鉴定。结果成功构建表达载体pET28a(+)/DHBV core,并表达DHBV core蛋白。获得2株稳定分泌抗DHBV core抗体的杂交瘤细胞株,分别为2D7和5G10,细胞培养液抗体效价为1∶400和1∶800。选择5G10细胞株制备单克隆抗体,小鼠腹水抗体效价可达1∶320 000。鸭肝组织免疫组化结果显示,DHBV病毒载量>1010copies/mg的肝组织中DHBV core蛋白的表达明显高于病毒载量<105copies/mg的肝组织,而未感染DHBV的鸭肝细胞内不表达DHBV core蛋白。亚型鉴定结果为IgG2aκ链。结论制备并获得了抗DHBV core蛋白的单克隆抗体,为DHBV core蛋白的功能研究、诊断试剂的研制与抗病毒治疗研究奠定了基础。

外周血T淋巴细胞及乙型肝炎病毒血清标志物与HBV-DNA的相关性分析

目的:探讨乙肝病毒血清标志物、外周血T淋巴细胞与HBV-DNA的相关性。方法:89例乙型病毒肝炎(简称乙肝)患者采用ELISA法检测乙肝病毒血清标志物HBsAg、HBsAb、HBeAg、HBeAb和HBcAb,采用流式细胞术测定T淋巴细胞亚群CD3^+、CD4^+和CD8^+,并采用荧光定量PCR法测定HBV-DNA,比较不同血清标志物模式间HBV-DNA阳性表达情况,并分析其相关性。结果:BsAg(+)、HBeAg(+)、HBcAb(+)组的HBV-DNA阳性率最高,为88.4%;HBV-DNA高浓度组CD3^+、CD4^+细胞百分比及CD3^+、CD4^+/CD3^+、CD8^+比值与HBV-DNA阴性组相比较低,差异具有统计学意义(P<0.05),CD3^+、CD8^+细胞百分比明显高于HBV-DNA阴性组,差异有统计学意义(P<0.05)。结论:HBV-DNA与T淋巴细胞及HBeAg检测相关性较好,联合检测乙肝血清标志物、外周血T淋巴细胞及HBV-DNA能提高乙肝的检出率,有助于全面监测乙肝病情及评价药物疗效。

乙肝患者血清抗原与抗体双阳性两对半模式与HBV-DNA和体液免疫检测结果分析

目的：探讨乙型肝炎病毒（HBV）感染者HBsAg阳性的血清学标志物少见模式与HBV-DNA和体液免疫的关系。方法：选择63例HBsAg阳性患者其血清中检出同一种抗原抗体同时存在（HBsAg与HBsAb同时阳性或 HBeAg与HBeAb同时阳性），以HBeAg是否阳性为标准分为2组：HBeAg阳性组（n=26）与HBeAg阴性组（n=37）。采用时间分辨免疫荧光分析法（TRFIA）定量测定乙型肝炎病毒血清标志物（HBV-M）；采用荧光定量聚合酶链反应（FQ-PCR）法检测HBV-DNA含量；采用Olympus AU6400全自动生化分析仪检测免疫球蛋白（IgG、IgA 、IgM）和补体（C3、C4）。结果：63例HBsAg阳性的血清学标志物少见模式表现为5种模式，以HBsAg（＋） HBsAb（＋）HBeAb（＋）HBcAb（＋）模式检出率最高，占52.38%（33/63）；各少见模式均不同程度地检出HBV-DNA；HBeAg阳性组HBV-DNA、IgG、IgM和C4与HBeAg阴性组比较差异有统计学意义（P〈0.05）；IgA和C3的差异均无统计学意义（P〈0.05）。结论：患者在慢性HBV感染过程中，血清出现抗原与抗体共存这一个特殊阶段，虽然有HBsAb的出现，但并不意味着HBV-DNA停止复制或传染性消失；不同血清学模式，其HBV复制和体液免疫水平是有差别的。

灰旱獭感染HBV的临床和病理分析

目的 探讨灰旱獭感染HBV后临床表现、病理改变及其相关关系。方法 ①用含HBV DNA人血清对健康灰旱獭攻毒 ,依次传代 ,分析其临床血清学变化与病理改变的相关性。②用合成HBcAg多肽分别接种 :对HBcAb- 旱獭单用多肽Ⅰ、Ⅱ或多肽Ⅰ、Ⅱ与HBV DNA同时注射 :对HBcAb+ 旱獭注射多肽Ⅰ、Ⅱ。结果 ①攻毒与传代后临床反应的轻重与肝脏病理变化的程度一致。②HBcAg多肽具有核心蛋白疫苗的作用。可激发抗体的形成 ,阻断HBV的攻毒 ,使HBcAb转阴 ,与肝组织炎症反应一致。结论 肝组织炎变与血清变化密切相关 ,证实攻毒、传代结果可靠。多肽具有阻断、干预灰旱獭感染HBV的作用。

HBV感染者血清HBcAgSPRIA测定的临床分析

目的 :研究HBcAg在HBV感染者中的阳性检出率、分布规律及与其他乙肝标志物的关系 ,探讨其在反映HBV复制及传染性和观察疗效方面的临床价值。方法 :采用SPRIA对461例HBV感染者进行血清乙肝六项指标测定 ,按其不同阳性结果分9种模式对比分析。结果 :HBV感染者中HBcAg阳性总检出率达50.75 % ,而未感染者及69例抗 -HBs单项阳性者中无阳性检出。结论 :SPRIA测定血清HBcAg在HBV感染者中的阳性检出具有特异性 ,并可作为疑有抗 -HBe阳性“逆转”为HBeAg阳性者的筛选检测 ,对判断HBV复制程度、病程、疗效及预后评估均有临床价值。

抗HBcAg人源性单链抗体细胞内表达及其抗病毒复制的实验研究

应用人源性抗HBcAg单链抗体细胞内表达技术 ,探讨抗HBV复制基因治疗的应用价值。应用噬菌体展示和基因重组技术 ,从HBV感染的外周血淋巴细胞克隆了人源性抗HBcAg单链抗体 ,并重组至逆转录病毒载体。以人肝癌细胞smmc - 772 1和PLC/PRF/5为靶细胞进行基因共转染 ,分别测定实验组细胞上清中的HBsAg和HBeAg ,与对照组做比较 ,观察抗HBcAg单链抗体细胞内表达的抗病毒治疗作用。结果显示 ,在急性HBV感染的细胞株中 ,抑制病毒复制效率为 4 9%～ 6 1% ,在慢性病毒感染细胞 ,抑制率为 4 1%～ 5 4 %。实验结果表明 ,应用单链抗体细胞内表达技术 ,在抗病毒治疗研究中具有潜在的应用价值。应对HBV的 4个开放阅读框架编码产物进行全面的对比研究 ,以发现抑制效率高。