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.     

Increased severity and morbidity of acute hepatitis in drug abusers with simultaneously acquired hepatitis B and hepatitis D virus infections

Hepatitis D virus (delta agent) markers were present in 111 (36%) of 308 intravenous drug abusers who were positive for hepatitis B surface antigen (HBsAg), 52 of these having hepatitis D virus antigenaemia. IgM antibody to hepatitis B core antigen (anti-HBc IgM) was present in 92 out of 95 subjects tested, indicating that hepatitis D virus and hepatitis B virus infections had been acquired simultaneously. Hepatitis D virus markers were present in three out of four patients with fulminant hepatitis, and in 80 of 223 (36%) with mild or moderate hepatitis compared with four of 29 (14%) of those who were asymptomatic. These proportional differences were significant (p less than 0.001). Hepatitis D virus markers were present in twice as many patients positive for anti-HBc IgM requiring admission to hospital with acute hepatitis compared with outpatients attending a drug treatment centre. Tests on one patient showed complete disappearance of HBsAg, but hepatitis D antigen (HDAg or delta antigen) and hepatitis B e antigen (HBeAg) were still present in serum samples. All five patients with chronic active hepatitis had hepatitis D antibody (anti-HD) compared with seven of 24 (29%) with chronic persistent hepatitis (p = 0.008). Blocking anti-HD persisted for long periods after simultaneous infections with hepatitis B virus and hepatitis D virus but at lower titres than in patients with chronic liver disease.     

Diagnostic and prognostic significance of the IgM antibody to the hepatitis delta virus

The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each of 70 patients with inflammatory liver disease and at a low titer in one of six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. The IgM antibody persisted in high titer over many years in patients with unremitting or progressive liver disease, but declined or disappeared before the homologous IgG antibody in the patients whose disease improved or resolved. Testing for IgM antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.     

急性起病的非甲非乙型病毒性肝炎的病原分析

对HBsAg(一)、IgM抗HAV(一)临床诊断为急性非甲非乙肝炎63例,进行了病原学鉴定。以聚合酶链反应(PCR)检测HBV DNA,HCV RNA,并检测了IgM抗HBc和抗HCV血清抗体。诊断为急性丙型肝炎15例(23.8％),急性乙型肝炎20例(31.7％),慢性HBV携带者急性活动19例(30.2％),乙、丙型混合肝炎2例(3.2％),病原不明7例(11.1％)。结果表明在临床所谓的急性非甲非乙肝炎中,急性和慢性乙型肝炎仍占多数。     

DIAGNOSTIC SIGNIFICANCE OF IgM ANTI-HBc DETECTION BY ELISA IN HBV INFECTION

This paper deals with an enzyme linked immuno- sorbent assay for the detection of IgM antibody to hepatitis B core antigen. The test was shown to be highly specific and sensitive. 109 hepatitis cases and HBsAg carriers were examined. Fifteen of 57 acute hepatitis cases, 16 0f 24 chronic persistent hepatitis cases, 8 0f 14 chronic active hepatitis cases, and 7 0f 14 carriers were positive. GMT of IgM anti-HBc in early acute hepatitis cases (>10-5) was significantly higher than that in chronic hepatitis cases(10_3.1) and carriers (10-2.45). The IgM anti-HBc could be classified into three types according to their serum reactions. IgM anti-HBc in high titer was of signifi- cant value. The dynamics of IgM anti-HBc and the comprehensive analysis of the HBV marker were emphasized. The use of IgM anti-HBc in diagnosis of hepatitis B is discussed.     

Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population

In 1981, a hepatitis B virus vaccine demonstration project was conducted in 1630 Yupik Eskimos in southwest Alaska. Levels of antibody to hepatitis B surface antigen and markers for hepatitis B virus infection in vaccinees were monitored yearly for 5 years. After 5 years of follow-up, 19% of those who initially had an immune response to vaccine of 10 sample ratio units or greater subsequently had levels of antibody to hepatitis B surface antigen lower than 10 sample ratio units. During the 5 years after the first dose of vaccine, in three responders and one person with an antibody to hepatitis B surface antigen response lower than 10 sample ratio units, antibody to hepatitis B core antigen developed, and the level of antibody to hepatitis B surface antigen was boosted. Hepatitis B surface antigen did not develop in any subjects, and none had clinical hepatitis. In the 5 years following the demonstration project, the annual incidence of hepatitis B virus infection decreased from 50 cases per 1000 population before the vaccine trial to 0.45 per 1000.     

慢性病毒性肝炎合并巨细胞病毒感染分析

[目的 ]探讨慢性病毒性肝炎合并巨细胞病毒感染对肝功能及病毒复制的影响 .[方法 ]分别检测了 3 2例慢性病毒性肝炎患者抗 巨细胞病毒IgM、乙型肝炎病毒血清学标志、抗 丙型病毒性肝炎抗体及生物化学指标 ;另选择 2 0例健康人 ,检测其抗 巨细胞病毒IgM ,与慢性病毒性肝炎患者的作对照 .[结果 ]慢性乙型肝炎病例中抗 巨细胞病毒IgM阳性率为 4 1% ,慢性丙型肝炎病例中抗 巨细胞病毒IgM阳性率为 4 0 % .血清抗 巨细胞病毒IgM阳性的慢性肝炎患者总胆红素、谷丙转氨酶水平及肝功能复常天数均明显升高或延长 ,并伴有发热、呕吐、黄疸、肝大症状或体征的加重 .[结论 ]巨细胞病毒感染好发于免疫虚损的宿主 ,又可抑制宿主免疫功能 ,有利于病毒复制 .合并巨细胞病毒感染可加重肝功能障碍 .     

Importance of markers of hepatitis B virus in alcoholic liver disease

To determine the importance of the presence of serological markers of hepatitis B virus infection in patients with alcohol related liver disease we compared cumulative alcohol intake and clinical and histological features in patients with markers of hepatitis B virus infection and in those without. Hepatitis B surface antigen (HBsAg) was detected in five (2%) out of 285 patients studied and antibody to HBsAg (anti-HBs) in 41 (14%); one patient had antibody to hepatitis B core antigen alone. The combined prevalence of markers of hepatitis B virus infection was similar in patients with alcoholic cirrhosis (18%) and precirrhotic liver disease (13%). Two patients positive for HBsAg had histological features of both alcoholic liver disease and chronic active hepatitis, with stainable HBsAg. Patients with anti-HBs were, however, histologically indistinguishable from patients without markers, and the mean cumulative alcohol intake of patients with anti-HBs was similar to or even higher than that of patients with liver disease of comparable severity who had no evidence of previous infection. The presence of markers of hepatitis B virus infection was related to former residence in countries with a high prevalence of the infection and to previous parenteral treatment and blood transfusions. Infection with hepatitis B virus does not enhance the development of chronic liver disease in heavy drinkers, except in the small number who remain positive for HBsAg.     

三峡工程施工区人群乙肝抗体水平调查

目的了解三峡工程施工区人群乙型肝炎(乙肝)抗体水平,评价乙肝疫苗接种效果,为大型水利工程施工制定乙肝的防治措施提供依据。方法采用现场流行病学调查和血清学调查相结合的方法。现场流行病学调查主要采用填写调查表,血清学调查主要是现场采样和实验室检测,实验室采用酶联免疫(ELISA)法检测乙肝抗体水平。结果共检测2 001份血清标本,总阳性率为61.5%,乙肝疫苗全程免疫注射后抗体阳性率为91.4%,未注射乙肝疫苗的抗体阳性率为41.0%。结论三峡工程施工区乙肝抗体总体水平较高,该施工区属于乙肝高流行区,全程(或部分)免疫注射后人群的乙肝抗体阳性率明显高于未注射人群,提示应进一步加强施工区乙肝疫苗预防接种工作。     

人-人嵌合抗丙肝抗体检测阳性对照品的研制及应用

目的:获得人-人嵌合型抗丙肝抗体的阳性对照品。方法:采集20例具有高抗体滴度的抗丙肝抗体阳性患者外周血,混合后分离外周血单个核细胞,TRIzol提取总RNA,逆转录合成cDNA。PCR分别扩增重链可变区和轻链可变区并以其为模板,获得ScFv,导入到PCANTAB 5E载体上构建噬菌体展示库。分别用NS3、NS4、NS5和core抗原对噬菌体库进行5轮的富集和淘洗;通过Phage ELISA的方法对单克隆菌落进行特异性鉴定,分别获得抗丙肝NS3、NS4、NS5抗体和两个抗丙肝core抗体。将ScFv的VH和VL分别克隆到pcDNA3.4载体上,构建人IgG全长抗体并通过Lipo3000转染293T细胞。收集细胞上清,经protein A纯化,保存于-80℃。结果:成功构建了抗丙肝抗体噬菌体库;筛选并表达了5个分别针对NS3、NS4、NS5和core抗原的阳性抗体,经验证表达的抗丙肝阳性抗体在-20°C~37°C表现稳定。多次重复冻融后不会影响抗体的使用效果。且5种抗体在国内外多种丙型肝炎检测试剂盒间测试均为阳性,具备一定的通用性。结论:获得5种人-人嵌合型抗丙肝抗体的阳性对照品且适用于多种丙型肝炎检测试剂盒。