叶下珠复方和拉米夫定治疗慢性乙型肝炎的临床疗效比较

[目的]观察比较叶下珠复方、拉米夫定、叶下珠复方合用拉米夫定治疗慢性乙型肝炎的疗效.[方法]90例慢性乙型肝炎患者随机分3组,分别为叶下珠复方组(剂量2.6g/次,3次/d)、拉米夫定组(剂量100mg/次,1次/d)和叶下珠复方合用拉米夫定组,均连续口服52周.治疗前、后定期检测血清肝功能指标及乙型肝炎标志物表面抗原(HBsAg)、e抗原(HBeAg)、乙型肝炎病毒脱氧核糖核酸(HBV-DNA)及酪氨酸-蛋氨酸-天冬氨酸-天冬氨酸(YMDD)含量.[结果]叶下珠复方组肝功能复常率、HBeAg转阴率均高于拉米夫定组,而HBV-DNA转阴率低于拉米夫定组(P<0.05),YMDD变异少于拉米夫定组(P<0.05);两药合用组的HBeAg转阴率与叶下珠复方组相仿(P>0.05)而高于拉米夫定组(P<0.01),HBV-DNA转阴率均高于叶下珠复方组和拉米夫定组(均P<0.01),肝功能复常率高于拉米夫定组(P<0.05或P <0.01),YMDD变异也少于拉米夫定组(P<0.05).[结论]叶下珠复方与拉米夫定联合用药可提高治疗慢性乙型肝炎疗效,减少YMDD变异,推迟和避免拉米夫定耐药株产生,以及由此而引起的病毒在体内的持续复制.     

Reversal of nonresponders and postexposure prophylaxis by intradermal hepatitis B vaccination in Japanese medical personnel.

Thirty-one Japanese nonresponders to subcutaneous hepatitis B vaccination and 15 medical personnel who were accidentally exposed to specimens positive for hepatitis B e antigen and were given hepatitis B immunoglobulin were intradermally immunized with 5 micrograms of plasma-derived hepatitis B vaccine every 2 weeks until delayed type hypersensitivity skin reaction to hepatitis B surface antigen became positive. Thirty (97%) of the 31 nonresponders developed delayed type hypersensitivity skin reactions to hepatitis B surface antigen after 2.3 +/- 1.2 (mean +/- SD) revaccinations. Twenty-nine (94%) of the 31 nonresponders had anti-hepatitis B surface antigen antibody levels greater than 10 IU/L. The immunoglobulin subclass of the antibody to hepatitis B surface antigen was mainly IgG1. After 1 year, 23 (74%) of the 31 nonresponders continued to have anti-hepatitis B surface antigen antibody levels greater than 10 IU/L. Persons accidentally exposed to specimens positive for hepatitis B e antigen developed delayed type hypersensitivity skin reactions to hepatitis B surface antigen following 3.1 +/- 1.1 revaccinations. None developed clinical hepatitis. There was no production of anti-hepatitis B core antigen antibody 1 year after exposure, indicating that protection was 100%. Intradermal hepatitis B vaccination is useful in reversing nonresponsiveness to hepatitis B surface antigen and for prophylaxis after exposure.     

282例HBV感染无症状表面抗原阳性者血清ALT与乙肝前S1抗原的检测

目的 了解乙型肝炎病毒(HBV)感染无症状表面抗原阳性者血清ALT和乙肝前S1抗原的状况.方法 用ELISA法检测血清标志物(HBsAg、抗HBs、HBeAg、抗HBe、抗HBc)和乙肝前S1抗原,用日立7060全自动生化分析仪检测血清ALT.结果 282例无症状表面抗原阳性者,乙肝前S1抗原总检出率为37.6％; ALT升高87例,占总人数的30.8％; ALT升高的87例患者中前S1抗原检出率为67.8％;ALT正常的195例患者中前S1抗原检出率为24.1％,两组比较差异有统计学意义(P＜0.01).在282例无症状表面抗原阳性者中,HBeAg阳性组,乙肝前S1抗原检出率为73.9％,ALT异常阳性率为52.2％;HBeAg阴性组,乙肝前S1抗原检出率为31.0％,ALT异常阳性率为25.6％,两组比较差异有统计学意义(P＜0.01).结论 乙肝病毒携带者不能完全排除ALT正常情况下的病毒复制;血清中出现HBeAb并不一定表示HBV复制停止.因此,对于无症状表面抗原阳性者应进行定期复查,监测其乙肝血清标志物、ALT和前S1抗原.     

南海官兵所驻岛礁甲、乙、丙和戊型肝炎病毒调查研究

目的了解我国南海官兵所生活岛礁的甲、乙、丙和戊型肝炎病毒分布情况。评估感染风险度,制定预防措施。方法 (1)上礁前,采集158名将上岛守礁官兵血清样本,进行常规肝炎病毒检测。(2)无菌采集上述158名上岛礁3个月后官兵的血液样本和礁上物体表面生理盐水样本390份,共548份。收集后保存于-20℃冰柜中,立即随补给船送回实验室进行乙型肝炎病毒DNA和甲、丙、戊型肝炎病毒RNA检测。结果 (1)158名守礁官兵上礁前检出血清甲肝抗体(lgG)阳性5人(3.16%);乙肝病毒表面抗原、丙肝和戊型肝炎抗体检测均为阴性。(2)上礁3个月以后,158份血清样本检出甲肝抗体阳性7份(4.43%),其中lgG阳性5份,lgM阳性2份(甲肝RNA为阳性);乙肝DNA检测有2份阳性(1.27%)。丙肝和戊型肝炎病毒RNA均为阴性。390份礁上的物体表面样本:检出甲、丙、戊肝病毒RNA阳性分别为24份(6.15%)、3份(0.77%)、2份(0.51%);乙肝病毒DNA阳性5份(1.28%)。结论守礁官兵所驻岛礁生活环境中存在甲、乙、丙、戊肝传染源,卫生部门要提高认识,有效地控制传染源,培养官兵良好的生活习惯,切断传染途径,预防守礁官兵病毒性肝炎传播和流行,并制定相应的病毒性肝炎流行治疗预案,配备治疗药品。     

孕妇血清中乙肝病毒抗原抗体检测与胎儿宫内感染的关系

目的：探讨孕妇血清中乙肝病毒抗原抗本，滴度与胎儿宫内感染发生率之间的关系，从而对母婴垂直传播提出适当的预防措施。方法：对855例孕妇采集肘静脉血，其分娩的新生儿出生后立即消毒脐带留取脐血，分别采用酶联免疫吸附法测定其乙肝表面抗原（HBsAg)，乙肝表面抗体（抗－HBs)，乙肝e抗原（HBeAg)，乙肝e抗体（抗－HBe)，乙肝核心抗体（抗－HBc)并对HBsAg,HBeAg，抗－HBc及HBsAg滴度与胎儿宫内感染的关系进行了分析。结果：855例孕妇HBsAg阳性者120例（占14．04％），120例HBsAg阳性孕妇的胎儿宫内感染率为32．50％（39／120）；孕妇血清中HBsAg滴度的高低与胎儿宫内感染率之间无显著性差异（P＞0．05），孕妇血清中单纯HBsAg阳性者发生胎儿宫内感染率为16．67％（1／6），HBsAg 阳性合并抗－HBc阳性者发生胎儿宫内感染率为12．32％（9／73），而孕妇血清中HBsAg阳性合并HBeAg阳性者发生胎儿宫内感染率为70．73％（29／41），与前组比较均有显著性差异（P＜0．01），结论：孕妇血清中HBsAg的滴度与胎儿发生宫内感染无关，但HBeAg阳性率越高，其胎儿发生宫内感染的机率就越大。     

酶联免疫法与胶体金法在乙肝表面抗原检测中的应用

目的探讨酶联免疫法与胶体金法在乙肝表面抗原检测中的应用价值。方法选取2018年1～7月我院健康体检人员血液标本780份,所有标本均采用真空管采集。运用酶联免疫法与胶体金法检测所有血液标本,统计分析酶联免疫法与胶体金法在乙肝表面抗原检测中的阳性情况,并对比酶联免疫法与胶体金法在乙肝表面抗原检测中的应用价值。结果酶联免疫法与胶体金法在乙肝表面抗原检测中的阳性率9.23%(72/780)、8.72%(68/780)之间差异不显著(P0.05)。将常规法设定为酶联免疫法,胶体金法在乙肝表面抗原检测中的敏感度为72.22%(52/72),特异度为97.74%(692/708),准确度为95.38%(744/780),阳性预测值为76.47%(52/68),阴性预测值为97.19%(692/712)。结论酶联免疫法与胶体金法在乙肝表面抗原检测中的应用价值相当,临床应该依据实际情况合理选择检测方法。     

拉米夫定等六种药物的体外抗乙型肝炎病毒作用

目的：观察拉米夫定（3TC）等6种药物对抗乙型肝炎病毒（HBV）体外药效评价及不同指标之间的关系。方法：利用乙型肝炎病毒基因转染的人肝癌细胞系2．2．15细胞,检测细胞培养上清液中的乙肝病毒表面抗原（HBsAg）、乙肝病毒e抗原（HBeAg)及乙肝病毒DNA（HBV－DNA）的含量作为药物抗HBV效果的观察指标。结果：（1）6种药物在一定浓度范围内对2．2．15细胞分泌的HBsAg和HBeAg抑制作用很弱或无抑制;（2）HBV－DNA定量检测拉米夫定和2′3′－二脱氧－3－氟鸟苷（FLG）对HBV DN水平有明显抑制作用,其半数有效剂量（IC50）分别为0．31μmol/L,0．53μmol/L,阿昔洛韦（ACV）和α－干扰素（α-IFN）之IC50分别为0．33mmo/L、96．18U／ml,膦甲酸钠（PFA）和利巴韦林（RBV）最大无毒浓度无任何抑制作用。结论：抑制HBsAg与HBeAg的病毒蛋白表达活性与抑制HBV DNA活性无一致相关性,以HBV DNA指标更能反映化合物的抑制作用。     

乙型肝炎病毒核心启动子缺失变异对病毒抗原表达的影响

目的：为研究乙型肝炎病毒（HBV）核心启动子（CP）20／21bp部分缺失（nt1748/1747至nt1767)及同时存在的A1896点变异对病毒抗原表达的影响。方法：利用前期构建的HBV全基因的重组载体转染HepG2细胞后,对病毒抗原进行ELISA检测及Western-blotting分析。结果：变异株分泌到细胞外的HBsAg,HBeAg及细胞内的HBcAg表达量较野毒株均明显减少。结论：HBV CP20／21bp部分缺失株及同时存在的A1896点变异株的病毒抗原表达较野毒株显著下降。     

Perinatal hepatitis B virus transmission in the United States. Prevention by passive-active immunization

Among infants born to women in whom sera are positive for both the hepatitis B surface antigen and the e antigen, 85% to 90% are infected with hepatitis B virus and become chronic hepatitis B surface antigen carriers. In a study to assess the effectiveness of passive-active prophylaxis (hepatitis B immune globulin and hepatitis B vaccine) of such infants, we screened 18,842 pregnant Asian-American women: 8.7% were positive for hepatitis B surface antigen and 3.0% were also positive for hepatitis B e antigen. Thus far, 113 infants have received hepatitis B immune globulin (0.5 mL at birth) and hepatitis B vaccine (three 20-micrograms doses beginning at birth or at 1 month) and have been followed up for nine to 18 months. Among these infants, 16 have become chronic carriers, an incidence of only 14.2%. All of the uninfected infants have retained high levels of antibody to surface antigen, suggesting that they have had an active immune response to the vaccine and should have long-term protection against hepatitis B virus.     

酶联免疫法检测乙肝PreS1抗原及抗体在乙肝诊断中的应用研究

目的探讨在乙肝诊断中使用酶联免疫法检测乙肝PreS1抗原及抗体的应用效果,为临床诊断提供更多的理论参考依据。方法选取乙肝两对半检查结果中的几种常见模式为样本,对它们采取酶联免疫法进行乙肝PreS1抗原和抗体的检测。结果大三阳患者,乙肝PreS1抗原阴性比例为11%,阳性比例则达到了89%;在小三阳患者中,PreS1抗原阳性患者占的比例为7%,同时在表面抗原以及核心抗体阳性中,所占比例大约14%,而在单纯表面抗原阳性样本里面所占比例约为5%。乙肝病毒的PreS1抗原与HBsAg,HBeAg和HBcAb具有相关性。结论 PreS1抗原和抗体的检测可以作为乙肝的两对半检查的相关补充检查,可以在了解以及尽早发现存在乙肝感染方面发挥重要作用。     

Study of the immunogenicity and infectivity of hepatitis B-containing stabilized plasma-protein solution

In early 1984, five patients who were undergoing plasmapheresis at a Melbourne hospital developed a transient hepatitis B surface antigenaemia. A common batch of stabilized plasma-protein solution (SPPS) that was included in the replacement therapy for each patient was found to contain hepatitis B surface antigen (HBsAg). A follow-up study was undertaken of these patients and others who were known to have received SPPS from the same batch (in total, 10 patients were followed for a median of 46.5 weeks). No patient developed evidence of hepatitis, although one patient developed antibody to surface antigen. It was concluded that the manufacturing process was effective in destroying the infectivity of the HBsAg-positive plasma that was used in this batch of SPPS and that the final product was poorly immunogenic in these patients.     

Relationship between hepatitis B virus DNA in blood and serological markers of hepatitis B infection

The hepatitis B virus (HBV) DNA dot-hybridization assay has been introduced into clinical practice in Australia and its behaviour compared with that of the classic markers of HBV infection. A good correlation exists between the presence of HBV DNA and that of hepatitis B e antigen but the degree of dissociation between HBV DNA and the e:anti-e system was smaller than earlier studies would suggest. Patients who are seronegative for hepatitis B surface antigen (HBsAg), whether they possess anti-HBs, anti-HBc HBc (antibody to the core antigen), or neither antibody, gave uniformly negative results for the presence of HBV DNA. Theses results are different from those that were obtained from earlier studies of patients with chronic liver disease.     

Efficacy of a mass hepatitis B vaccination program in Taiwan. Studies on 3464 infants of hepatitis B surface antigen-carrier mothers

To evaluate the efficacy of the mass hepatitis B vaccination program in Taiwan in interrupting perinatal hepatitis B virus transmission, 3464 randomly selected 18-month-old infant vaccinees born to hepatitis B surface antigen-carrier mothers were recruited from 9697 eligible infants during a six-month period of the program. They were divided into ten groups according to maternal infectivity and compliance with the vaccination schedule. Serum samples were tested for hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen. In 786 infants who had highly infectious mothers and who received hepatitis B immune globulin and vaccine on schedule, the protective efficacy was about 85%. The efficacy seemed to be slightly lower in those immunized off schedule. Overall, 11% of infants still carried hepatitis B surface antigen, and 81% of the infants had antibody to hepatitis B surface antigen that exceeded 10 mIU/mL in more than 90% of them. The geometric mean titers of antibody to hepatitis B surface antigen were more than 200 mIU/mL in every group of infants. We conclude that the mass vaccination program is efficacious in preventing perinatal hepatitis B virus transmission and the chronic carrier state; most infant vaccinees have adequate levels of protective antibody at 18 months of age. This program is extremely significant in the control of hepatitis B virus infection in Taiwan.     

Efficacy of a heat inactivated hepatitis B vaccine in male homosexuals: outcome of a placebo controlled double blind trial

The efficacy of a heat inactivated hepatitis B virus vaccine, containing 3 micrograms hepatitis B surface antigen (HBsAg), was studied in a high risk group of 800 susceptible homosexual men by a randomised placebo controlled double blind trial. At the trial end point (21.5 months), 17 hepatitis B virus infections had occurred in vaccinated subjects (attack rate 4.8%) and 56 in subjects receiving a placebo (attack rate 23.8%). This reduction in the incidence of hepatitis B virus infections in vaccinated subjects was highly significant (p less than 0.0001). Two months after the first injection 72.3% of the vaccinated subjects had formed antibodies against hepatitis B surface antigen, and this percentage increased to 89% at four months. Maximum anti-HBs titres were reached five months after the first vaccination, the geometric mean titre being 107.6 mIU. Even vaccinated subjects with a low antibody response (greater than or equal to 1 and less than 10 mIU) were found to be protected from HBsAg-positive infections. The vaccine had no serious side effects.     

Hepatitis B virus DNA and e antigen in serum from blood donors in the United Kingdom positive for hepatitis B surface antigen

Serum samples from 214 blood donors in the United Kingdom who were carriers of hepatitis B surface antigen (HBsAg) were examined for hepatitis B virus deoxyribonucleic acid (DNA) by DNA:DNA hybridisation and for hepatitis B e antigen (HBeAg) and its antibody. One fifth of the donors carried infectious virus in their circulation. The presence of hepatitis B virus DNA correlated well with that of HBeAg, although hepatitis B virus DNA was found in five serum samples that were negative for HBeAg. It is concluded that analysis of serum samples for hepatitis B virus DNA by hybridisation should be the method of choice for determining whether carriers of HBsAg are infectious.     

柔肝煎联合拉米夫定对慢性乙型肝炎患者E抗原及乙型肝炎病毒复制指标的影响

目的：观察自拟中药方剂柔肝煎对慢性乙型肝炎患者E抗原及乙型肝炎病毒复制的影响。方法：将65例慢性乙型肝炎患者随机分为治疗组和对照组,治疗组35例以柔肝煎联合应用拉米夫定治疗,对照组30例单纯应用拉米夫定治疗,疗程均为6个月,观察治疗前后E抗原及乙型肝炎病毒复制等指标的变化。结果：两组血清乙型肝炎病毒阴转率未见显著差别（P〉0.05）,但治疗组HBeAg阴转率及ALT复常率均显著高于对照组（两组P值均小于0.01,有统计学差异）,且未发现明显不良反应。结论：柔肝煎联合应用拉米夫定对慢性乙型肝炎患者病毒血清学指标及肝功能指标的控制总体效果好于单纯应用拉米夫定,且安全性好。     

Hepatitis B virus infection among street youths in Montreal

BACKGROUND: Street youths are at high risk for many health problems, including sexually transmitted diseases and bloodborne infections. The authors conducted a cross-sectional anonymous study from December 1995 to September 1996 involving street youths in Montreal to estimate the prevalence of risk behaviours for hepatitis B virus (HBV) infection and of markers of past and present HBV infection. METHODS: Participants were 437 youths aged 14 to 25 meeting specific criteria for itinerancy who were recruited in collaboration with the 20 major street youth agencies in Montreal. Sociodemographic and lifetime risk factor data were obtained during a structured interview, and a blood sample was taken to test for HBV markers (hepatitis B surface antigen and antibodies to the hepatitis B core antigen). Univariate analyses and multivariate logistic regressions were conducted. RESULTS: The mean age of the subjects was 19.5 years; 69.3% (303/437) were males. Many subjects had high-risk behaviours: 45.8% (200/437) had injected drugs, 24.5% (107/436) had engaged in prostitution, and 8.7% (38/437) reported having a sexual partner with a history of unspecified hepatitis. The prevalence rate for one or both HBV markers was 9.2% (40/434) (95% confidence interval [CI] 6.7%-12.3%). Multivariate logistic regression analysis showed that being over 18 years of age (adjusted odds ratio [OR] 4.5, 95% CI 1.8-11.7), having injected drugs (adjusted OR 3.5, 95% CI 1.5-8.3) and having had a sexual partner who had unspecified hepatitis (adjusted OR 3.2, 95% CI 1.3-7.5) were all associated with HBV infection. INTERPRETATION: Street youths are at high risk for HBV infection. Early and complete HBV vaccination among this vulnerable population is urgently needed.     

乙型肝炎病毒核心启动子缺失变异对病毒抗原表达的影响

目的为研究乙型肝炎病毒(HBV)核心启动子(CP)20/21bp部分缺失(nt1748/1747至nt1767)及同时存在的A1896点变异对病毒抗原表达的影响。方法利用前期构建的HBV全基因的重组载体转染HepG2细胞后,对病毒抗原进行ELISA检测及Western-blotting分析。结果变异株分泌到细胞外的HBsAg、HBeAg及细胞内的HBcAg表达量较野毒株均明显减少。结论HBVCP20/21bp部分缺失株及同时存在的A1896点变异株的病毒抗原表达较野毒株显著下降。     

乙肝DNA定量及五项与S1抗原联合检测的临床意义

目的:探讨乙肝五项、乙肝DNA定量(HBV-DNA)与乙肝前S1抗原联合检测的临床意义,为其临床的诊断提供参考。方法:175例入住我院肝病科患者作为研究对象,采用酶联免疫吸附法及定量法对空腹抽取的肘静脉血进行乙肝前S1抗原、乙肝五项及HBV-DNA检测,评价其对乙型肝炎病毒感染的诊断价值。结果:不同乙肝五项模式下,乙肝前S1抗原与HBV-DNA的检测结果比较差异无统计学意义(P<0.05),在40例HBsAg、HBeAg、抗-HBc阳性的标本中检出乙肝前S1抗原和HBV-DNA的阳性率分别为90.0%和82.5%;在76例HBsAg、抗-HBe、抗-HBc阳性的标本中检出乙肝前S1抗原和HBV-DNA的阳性率分别为64.5%和56.6%。在30例HBcAb阳性患者中检出有部分患者乙肝前S1抗原阳性,表明HBeAg阴性的患者无论HBeAb阳性或阴性均有可能存在病毒的复制。90例HBeAg阳性患者有71.1%乙肝前S1抗原阳性,82.2%HBV-DNA阳性。结论:乙肝五项、乙肝DNA定量与乙肝前S1抗原联合检测可以更好地诊断乙肝,值得临床推广应用。     

前列腺素E1联合糖皮质激素治疗乙型重型肝炎临床分析

目的:探讨前列腺素E1联合糖皮质激素(以下简称激素)治疗乙型重型肝炎的临床疗效。方法:将我院2006年10月～2011年5月收治的70例重症肝炎的患者随机分为两组,对照组患者给予常规药物与激素联合治疗,观察组患者在对照组治疗方法的基础上联合前列腺素E1治疗,比较两组患者的治疗效果。结果:观察组患者采用联合治疗后,其凝血酶原活动度明显上升,好转率达85.71%,各指标与对照组比较差异具有统计学意义。结论:采用前列腺素E1与激素联合治疗乙型重型肝炎能够取得更好的治疗效果,值得在临床应用。