HBV前S1抗原在乙型肝炎临床诊断中的意义

目的探讨乙型肝炎(乙肝)病毒前S1抗原在乙肝病毒感染中的临床意义。方法分析1088例HBV前S1抗原阳性结果与乙肝5项病毒学指标和HBV DNA结果的关系。结果前S1抗原阳性的乙肝5项病毒学指标结果出现6种模式,其中HBsAg、HBeAg、抗HBc阳性患者的前S1抗原阳性率为88.74%;HBsAg、抗HBe、抗HBc阳性患者前S1抗原阳性率为41.32%,2组间有显著差异(P<0.05),而HBsAg及抗HBc阳性组前S1抗原阳性率介于HBsAg、HBeAg、抗HBc阳性组与HBsAg、抗HBe、抗HBc阳性组之间。HBsAg、HBeAg、抗HBc阳性患者前S1抗原阳性率随着HBV DNA载量的升高而增加(各组间P<0.05)。HBeAg、前S1抗原与HBV DNA三者间有很好的一致性。结论检测前S1抗原是对HBsAg、HBeAg及HBV DNA检测的重要补充。在防止乙肝漏诊、误诊及了解疾病的转归等方面都具有重要的临床意义。     

前S1抗原在乙肝病毒感染与复制中的作用

目的 传统乙肝血清标志物是目前我国用于乙肝检测与筛查较普及的指标,但传统乙肝HBV-M检测在病毒复制等一些方面尚有不足.本研究分析前S1（Pre-S1）抗原在判断乙肝病毒的感染与复制中的作用.方法 HBV-M和Pre-S1抗原检测采用ELISA法;HBV DNA检测采用实时荧光定量PCR技术.结果 （1）Pre-S1抗原在乙肝病毒早期感染中的作用：787例ALT正常血清中,Pre-S1抗原阳性34例,HBV-M检测HBsAg（＋）2例,HBsAg（＋）、HBeAg（＋）1例,HBsAg（＋）、HBeAg（＋）、HBcAb（＋）7例,HBsAg（＋）、HBeAb（＋）、HBcAb（＋）18例,HBsAg（＋）、HBcAb（＋）4例,HBV DNA阳性35例,三者检出结果高度符合,无显著差异（P＞0.05）.（2）Pre-S1抗原在乙肝病毒复制中的作用：816例慢性乙肝患者中,HBeAg（＋）/HBeAb（-）396例,Pre-S1抗原阳性357例,HBV DNA阳性371例,阳性检出率分别为90.1%和93.6%.HBeAg（-）/HBeAb（＋）285例,Pre-S1抗原阳性223例,HBV DNA阳性247例,阳性检出率分别为78.2%和86.7%.HBeAg（-）/HBeAb（-）135例,Pre-S1抗原阳性85例,HBV DNA阳性105例,阳性检出率分别为62.9%和77.7%,若以HBV DNA≥103copy/ml为判断乙肝病毒存在复制的标准,则Pre-S1抗原的检出率为79%（414/525）,HBeAg（＋）的检出率为32.7%（172/525）;Pre-S1抗原、HBeAg（＋）与HBV DNA的总符合率分别为78.8%（615/723）、45.5%（327/723）,HBV DNA与Pre-S1抗原检出率差异无显著性（P＞0.05）,HBeAg（＋）与HBV DNA检出率差异有显著性（P＜0.05）.结论 Pre-S1抗原是乙肝病毒早期诊断与病毒复制的重要标志.     

60例孕妇HBV血清标志物水平与母婴传播的关系分析

目的 探讨孕妇乙型肝炎病毒（HBV）血清标志物水平与母婴传播的关系。方法 采取60例孕妇、脐带、新生儿血清用美国雅培试剂做HBV血清标志物（HBVM）包括：HBsAg、HBsAb、HBeAg、HBeAb、HBcAb定量分析,用荧光定量PCR法测HBV DNA。结果 HBsAg、HBeAg、HBcAb阳性母亲的新生儿脐血HBV M阳性率91．67％,新生儿血HBV M阳性率85％,母血HBsAg、HBeAg、HBcAb滴度显著高于脐血、新生儿血,且母血、脐血、新生儿血HBV M水平依次降低;HBV DNA阳性率也依次降低,分别为58、33％、10％、6、67％,滴度也依次降低。HBsAg、HBeAb、HBcAb阳性母亲,HBsAg、HBcAb阳性母亲和单项HBsAg阳性母亲的新生儿脐血、新生儿血HBV M阳性率较低。新生儿血以HBeAg阳性为主,滴度明显高于正常值,HBsAg滴度仅略高于正常值。结论 母婴垂直传播与母亲HBeAg高滴度有密切关系,与母亲HBV DNA阳性或阴性关系并不十分密切。检测脐血和新生儿血HBsAg、HBV DNA阴性并不能排除HBV感染,不如检测HBsAg、HBeAg更有意义,更经济。     

乙型肝炎相关性肝脏疾病肝移植术后乙肝病毒复发的预防

目的通过乙型肝炎相关性肝脏疾病患者在拉米夫定联合乙型肝炎高效免疫球蛋白（HBIG）治疗下供肝植入前后受体乙型肝炎标志物变化，HBV基因序列变化检测，探讨其预防受体HBV再感染的效果。方法采用MEIA法、PCR-微流芯片法，基因测序法检测21例受体手术前后血清HBV—M、HBV—DNA定量、HBV—YMDD、HBVS基因α决定簇变异，同时采用ELISA法检测供体血清HBV—M。结果术前21例受体HBsAg、HBeAg／HBeAb、HBcAb阳性，16例HBV-DNA阳性，1例HBV．DNA阴性，4例HBV．DNA未测，术后19例患者HBV-M变成HBsAb或HBsAb、HBcAb阳性，1例为HBsAg、HBeAg、HBcAb阳性，1例为HBsAg、HBeAb、HBcAb阳性，其中19例HBV-DNA阴性，2例HBV-DNA阳性，无一例术前、后出现HBV．YMDD、HBVS基因α决定簇变异，供肝HBV-M均阴性。结论拉米夫定联合HBIG预防肝移植术后乙肝复发疗效确切，乙肝低或无复发可能与供体HBV-M阴性及受体无HBVS基因d决定簇变异有关，术前受体HBV-DNA结果与术后乙肝复发相关性未显示。     

化学发光法检测77 286例乙型肝炎病毒血清标志物结果分析

目的探讨长春市人口乙肝病毒（HBV）感染率及血清标志物的表达模式。方法采用化学发光法对2006年7月～2009年7月就诊患者的77286份血清标本进行HBsAg、HBsAb、HBeAg、HBeAb、HBcAb检测。结果 HBV的感染率为5.93%,血清标志物共有13种模式,感染期模式占前三位的是：HBsAg、HBeAb、HBcAb均为阳性占6.26%,HBsAg、HBeAg、HBcAb均为阳性2.64%;HBsAg、HBcAb阳性占0.20%;恢复期模式前三位的是：HB-sAb阳性占39.47%;HBsAb、HBeAb、HBcAb均为阳性占15.65%;HBsAb、HBcAb阳性者占13.42%。结论长春市人口乙型肝炎病毒情况不容乐观,需进一步加强宣传教育,普及知识,强化免疫,降低乙肝发病率。     

血液系统恶性肿瘤患者乙型肝炎病毒感染的临床分析

目的:回顾性分析乙型肝炎病毒(HBV)感染在住院的血液系统疾病患者中分布情况及化疗后影响。方法:对205例血液系统疾病患者临床资料进行回顾性分析,根据血液系统疾病及乙肝病毒抗原、抗体检测结果不同分组,以200例同期体检人员为对照,统计总体乙肝病毒感染率及治疗后肝功能损害情况。结果:淋巴瘤组HBsAg阳性率为22.95%,与体检组及其他疾病组差异有统计学意义(P<0.05);治疗前肝功能异常发生率HBV感染组为14.67%,HBV未感染组的5.38%,差异有统计学意义(P<0.05);治疗后肝功能损害发生率HB-sAg阴性HBeAb、HBcAb阳性组为51.28%,HBV未感染组为22.31%,两者差异有统计学意义(P<0.05)。结论:淋巴瘤患者中HBV感染率明显增高。对予HBsAg阳性患者,早期应用抗病毒药物拉米夫定并加强护肝治疗能有效降低HBV-DNA激活及肝功能损害发生率。HBsAg阴性而HBeAb、HbcAb阳性患者临床医生应提高警惕,早期检测HBV-DNA,加强护肝治疗强度,定期监测HBV-DNA及肝功能。     

血清乙肝五项不同表达模式原发性肝癌R0切除术患者的预后分析

目的分析血清乙肝五项不同表达模式原发性肝癌(HCC)R0切除术患者的预后。方法 343例HBV相关HCC均行R0切除术,分析其血清乙肝五项表达模式与预后的关系。结果小三阳(HBsAg、HBeAb、HBcAb阳性)、1+5阳性(HBsAg、HBcAb阳性)、大三阳(HBsAg、HBeAg、HBcAb阳性)、其他模式患者的总生存期(OS)分别为69.0、27.9、84.0、72.0个月,无瘤生存期(DFS)分别为32.2、17.8、84.0、42.0个月。血清乙肝五项不同表达模式患者的OS、DFS比较,P均<0.05。结论血清乙肝五项不同表达模式HCC R0切除术患者的预后不同,其中以HBsAg、HBeAb阳性者预后最差。     

慢性乙型肝炎患者HBV血清标志物与HBV DNA的相关性分析

目的探讨慢性乙型肝炎患者HBV血清标志物(HBV serum markers,HBV-M)HBsAg、HBeAg、HBeAb、HBcAb和HBcAb IgM含量与HBV DNA水平的相关性,为临床诊断和治疗提供依据。方法采用化学发光微粒子免疫测定法和荧光定量聚合酶链反应分别检测446例慢性乙型肝炎(chronic hepatitis B,CHB)患者血清HBsAg、HBeAg、HBeAb、HBcAb含量和HBV DNA水平,同时检测54例HBcAb IgM阳性患者的血清HBV DNA水平,统计分析HBV-M含量与HBV DNA水平的相关性。结果①CHB患者血清中,HBsAg和HBeAg含量与HBV DNA水平呈正相关(P<0.05),HBeAb和HBcAb含量与HBV DNA水平未见相关性(P>0.05);②HBcAb IgM阳性患者中HBcAb IgM含量与HBV DNA水平亦未见相关性(P>0.05)。结论 CHB患者血清HBsAg和HBeAg含量与HBV DNA水平呈正相关。定量检测HBV-M和HBV DNA能更好地了解HBV的动态变化,对诊断和治疗有重要指导意义。     

定量PCR检测血清中乙型肝炎病毒DNA及其意义

目的检测血清中乙型肝炎病毒DNA拷贝数,并了解HBV感染的不同血清学指标组合相应的HBV DNA含量分布,以指导临床。方法 采用定量PCR和定性PCR方法,检测216份不同临床类型血清标本的HBV DNA,再用ELISA方法测定HBV-M,统计不同免疫指标组合的HBV DNA平均含量。结果病毒量分为高、中、低三度,大于107拷贝mL-1为高滴度:107-105拷贝mL-1为中等滴度;105拷贝mL-1以下为低滴度。60例HBsAg(+)HBeAg(+)HBcAb(+)血清,HBV DNA全部阳性,平均含量为1.9×108拷贝mL-1。51例HBsAg(+)HBeAb(+)HBcAb(+)血清,HBV DNA平均含量为5.4×106拷贝mL-1;33例HBsAg(+)HBeAb(+)血清,HBV DNA平均含量为7.5×105拷贝mL-1;114例HBsAb(+)HBeAb(+)HBeAb(+)血清,HBV DNA平均含量为1.8×105拷贝mL-1。定性和定量PCR阳生率分别为59.3％和61.6％。两种方法相对符合率为94.5％。结论定量PCR可真实反应HBV感染、复制及病程变化,对乙型肝炎临床诊断及治疗均有较大的指导意义。     

襄阳地区无偿献血者乙型肝炎病毒核酸检测效果分析

目的:分析核酸检测(NAT)献血者乙型肝炎病毒(HBV)结果,探讨血站全面开展NAT的必要性。方法:对我站酶免检测无反应性标本,采用PCR-荧光法进行NAT检测,NAT有反应性标本做HBV DNA定量和乙肝"两对半"检测。结果:NAT 31 443份标本,有反应49例(0.16%),其中,HBV DNA定量检测有反应性标本30例,"两对半"定性实验结果为22例HBsAg有反应性,14例HBsAg为临界值的标本,且其中32例合并HBeAb、HBcAb有反应性;13例HBsAb、HBeAb或HBcAb有反应性。结论:NAT能够在一定程度上弥补ELISA方法的局限性,有效缩短窗口期,防止亚型变异或者隐匿性肝炎漏检的风险,有必要在血站全面开展。     

难治性慢性乙型肝炎

"难治性慢性乙型肝炎"的定义:符合慢性乙型肝炎的诊断标准,因各种原因/因素导致在现有指南或建议治疗方案指导下,使用了包括核苷(酸)类似物和(或)干扰素在内的抗HBV药物治疗失败或疗效不佳、或不规范抗病毒治疗所致、或已有循证医学依据证实疗效不佳的慢性乙型肝炎.难治性慢性乙型肝炎概念的提出,有利于乙型肝炎患者接受临床规范化...     

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma

This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen (HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg-negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and four (18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface (S), core (C), polymerase (P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%) patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or only in the nontumorous liver (one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg-negative, anti-HCV-positive HCCs, including three (10%) who were also negative for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV-associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs.     

Analysis of differential gene expression between chronic hepatitis B patients and asymptomatic hepatitis B carriers

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection remains a serious global health problem, inducing a spectrum of diseases, including asymptomatic HBV carriage (ASC) and chronic hepatitis B (CHB). ASC and CHB represent different immunological states and their prognoses are diverse. To clarify molecular mechanisms underlying the two infection states, the differentially expressed genes between the two states were screened and identified. METHODS: Subtracted complementary DNA libraries by suppression subtractive hybridization, dot blot hybridization and quantitative real-time PCR were used to identify the differentially expressed genes between subjects with CHB and those with ASC. RESULTS: RNA from peripheral blood mononuclear cells from CHB and ASC subjects was subjected to suppression subtractive hybridization and resulted in isolation of subtracted complementary DNA clones. Eighty-eight randomly sampled clones were rescreened by dot blot hybridization, from which 29 clones were identified as differentially expressed genes. The differential expression of three genes was confirmed by real-time PCR in 23 subjects with CHB and 21 with ASC. CONCLUSIONS: Differentially expressed genes in peripheral blood mononuclear cells between CHB and ASC have been isolated by suppression subtractive hybridization, including some new genes. Of the up-regulated genes in CHB, most are known to be responsive to inflammatory conditions. These genes might provide clues in elucidating the mechanisms of the two different HBV infection states and designing therapeutic targets for HBV infection.     

Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients

BACKGROUND/AIMS: Long-term clinical outcomes of occult hepatitis B virus (HBV) infection were studied. METHODS: Fifteen chronic hepatitis B patients were monitored for a median of 4.4 years (range 0.9-15.3) after hepatitis B surface antigen (HBsAg) seroclearance. Serum HBV DNA was measured by real-time detection polymerase chain reaction. Thirteen patients underwent liver biopsies at the end of follow-up and liver histology was evaluated by Ishak score. Liver HBV DNA was also measured for 12 patients. RESULTS: At the end of follow-up, HBV viremia was absent in 13 (87%) patients, and antibody titers to hepatitis B core antigen showed an inverse correlation with time from HBsAg seroclearance (r=-0.554; P=0.0040). However, all patients retained liver HBV DNA and tested positive for the covalently closed circular HBV DNA replicative intermediate. The hepatic HBV DNA loads had no relation to liver histology. Paired biopsies from 11 patients disclosed that each necroinflammatory score significantly improved after HBsAg seroclearance. Amelioration of liver fibrosis was also evident in eight (73%) patients (P=0.0391 by signed rank test). CONCLUSIONS: A long-standing but strongly suppressed HBV infection may confer histological amelioration after HBsAg seroclearance.     

HBV感染者HCV的重叠感染关系研究

目的 研究HBV感染患者中HCV的重叠感染状况及其相互关系。 方法 采用ELISA法对767例HBV感染患者同步检测HBV和HCV血清标志物,对可疑HCV感染但抗HCV阴性和/或抗-HCV阳性患者血清,采用PCR法检测HCV-RNA。 结果 HCV重叠感染率为4.82％,且在各类乙肝患者中存在非常显著差异(P<0.01);HBV/HCV感染组重症肝炎的发生率显著高于非HCV感染组(P<0.01);HBV/HCV感染组HBsAg阳性率显著低于单纯HBV感染组(P<0.05);HBV/HCV感染组HCV-RNA阳性率显著低于单纯HCV感染组(P<0.05)。 结论 HCV重叠感染与乙肝患者的发病、病情加重及重症肝炎的发生相关;HCV可抑制或中止HBsAg携带状态,但这种作用远不如对病情的加重作用重要;同时HBV对HCV的复制亦存在抑制作用。     

成人急性乙型肝炎抗病毒治疗的探讨

成人急性乙型肝炎大多呈自限性病程,但有5％-10％的慢性化几率,本文针对成人感染乙型肝炎病毒后是否需要抗病毒治疗、抗病毒治疗的时机、适应的患者群以及如何进行抗病毒治疗作一综述。     

Novel hepatitis B virus surface antigen mutations associated with occult genotype B hepatitis B virus infection affect HBsAg detection

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty‐seven hepatitis B surface antigen (HBsAg)‐positive/HBV DNA‐positive blood donors served as control group for comparison. Occult HBV‐related mutations with a high incidence (P < .05) in the S gene were identified. To further verify these occult infection‐related mutations, a conservative full‐gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection‐related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P < .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P < .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P < .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P < .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.     

Clinical outcomes of chronic hepatitis B patients with persistently detectable serum hepatitis B virus DNA during lamivudine therapy

BACKGROUND AND AIM: A small proportion of chronic hepatitis B patients have persistently detectable serum hepatitis B virus (HBV) DNA despite lamivudine therapy. The incidence and clinical outcomes of patients who persistently have detectable serum HBV-DNA during lamivudine therapy was investigated. METHOD: We enrolled 221 chronic hepatitis B patients who underwent lamivudine therapy for more than 6 months. Among them, 180 were HBeAg positive. Serum HBV-DNA, HBeAg, anti-HBe and alanine aminotransferase (ALT) levels were serially monitored. The study groups were defined, using a hybridization assay, as patients with reductions in serum HBV-DNA below the detectable level (group I) or patients with persistently detectable serum HBV-DNA (group II) during the initial 6 months of lamivudine therapy. RESULTS: The incidence of patients who had persistently detectable HBV-DNA was 7.7%. After the first year, the rates of viral breakthrough, HBeAg loss and serum ALT normalization of group I versus group II were 21% versus 63%, 38% versus 0%, and 71% versus 28%, respectively (P < 0.001). The log(10) reduction of serum HBV-DNA at 6 months was -4.58 log(10) for group I and -1.97 log(10) for group II (P < 0.001, bDNA assay). There were no pretreatment lamivudine-resistant mutants in group II. CONCLUSION: Lamivudine had little effect on serum HBV-DNA suppression, viral breakthrough suppression and rate of HBeAg loss and ALT normalization in chronic hepatitis B patients with persistently detectable serum HBV-DNA during the initial 6 months of therapy. Early termination of lamivudine therapy is advocated for these patients.     

Development of transient autoimmune hepatitis during interferon treatment of chronic hepatitis B

Summary A 42-year-old man was treated with interferon- for chronic hepatitis B; during the fourth week of treatment he developed an exacerbation of liver disease, and nuclear and smooth muscle autoantibodies, which were previously negative, were detected in very high titers. After discontinuation of interferon therapy, ALT values subsided promptly and autoantibodies disappeared within a few months. This sequence of events strongly suggests a direct relationship between IFN treatment and a self-limited hepatitis with autoimmune markers in this case.