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1.
Eleven male fulminant hepatitis (FH) patients (mean age: 47.7 +/- 16 years) positive for hepatitis B surface antigen (HBsAg) but negative for IgM antibody to hepatitis B core antigen (IgM anti-HBc) were admitted consecutively to the Athens Hospital for Infectious Diseases between May 1981 and November 1983. Because of the absence of IgM anti-HBc, determined by an enzyme immunoassay, these patients were considered to be HBsAg carriers with a superimposed acute hepatitis. Three of the 11 patients received immunosuppressive chemotherapy during the six months before the onset of the acute hepatitis. None of the patients was homosexual or a drug addict. Infection with hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis delta virus (HDV) was detected with serologic markers and/or molecular hybridization techniques. Fulminant hepatitis was attributed to spontaneous reactivation of chronic hepatitis B in four patients, chemotherapy-induced reactivation of chronic hepatitis B in three patients, HDV superinfection in one patient and possible superinfection by non-A, non-B agent(s), HDV, or HDV-like agents in three patients. Reactivation of chronic hepatitis B was an important cause of apparent acute hepatitis in heterosexual male HBsAg carriers from an area with a high prevalence of HBV infection.  相似文献   

2.
Chronic hepatitis B surface antigen (HBsAg) carriers run a high risk of developing chronic liver disease after renal transplantation. To determine the impact of liver disease on long-term morbidity and mortality of HBsAg carriers following kidney transplantation we analyzed 1977 patients, including 76 HBsAg carriers, who underwent renal transplantation during the period 1968–1992. Although the HBsAg carriers had a better 5-year patient and graft survival rate (94% and 83%) than HBsAg-negative patients (87% and 61%), the prognosis was poor after the tenth year of transplantation. Transplant loss is more frequently caused by death of the HBsAg carriers, in contrast to the total population (34% vs 17% for HBsAg-negative patients). Death occurs in 73% of cases due to complications of hepatitis B. In the HBsAg-negative patients, the predominant cause of death is cardiovascular failure (51% vs 11% in HBsAg carriers), whereas only 2% died of liver disease. Kidney transplantation in HBsAg carriers with normal liver function appears to be justified because of rare graft loss due to acute rejection, low early morbidity and mortality, and late onset of fatal hepatic deterioration.Abbreviations HBsAg hepatitis B surface antigen - HBV hepatitis B virus - HBeAg hepatitis B e antigen - GOT glutamic oxaloacetic transaminase - GPT glutamic pyruvate transaminase - GLDH glutamate dehydrogenase - AP alkaline phosphatase - GGT gamma-glutamyl transferase - CHE buturyl cholinesterase - LDH lactate dehydrogenase - HBc hepatitis B core - HDV hepatitis delta virus - HCV hepatitis C virus - CsA cyclosporine A - Aza azathioprine - RIA radioimmunoassay - HD haemodialysis - KTx kidney transplantation - LTx liver transplantation - CMV cytomegalovirus Correspondence to: V Kliem  相似文献   

3.
Asymptomatic blood donors with persistent HBs antigenaemia have a variety of histological lesions in the liver, and serial biopsies indicate that, in some, these lesions may progress. The immunoperoxidase technique was found to be a sensitive method for the histological demonstration of HBsAg and HBcAg. Livers showing minor histological changes contained more HBsAg than those with active lesions and there appears to be an inverse relationship between the amount of HBsAg in the liver and the severity of the histological damage. In the carriers who had more than one biopsy, the presence of stainable HBsAg, irrespective of the initial histological diagnosis, was associated with a greater likelihood of progression of the histological lesion. HBcAg was found only in the hepatocyte nuclei of carriers with chronic aggressive and chronic persistent hepatitis.  相似文献   

4.
The PEG-trypsinization assay detected HBsAg-CICs in 31 out of 44 (70%) patients with acute hepatitis B, in five out of 107 (5%) asymptomatic HBsAg carriers and, in addition, in both patients with HBsAg-positive chronic liver disease. A close correlation between the levels of HBsAg-CICs and disease activity was observed. The clinical course, parameters of liver function tests and outcome of the disease in patients without HBsAg-CICs (group A) and in patients with transient HBsAg-CICs (group B) were essentially similar. In contrast, patients with persistent HBsAg-CICs (group C) had a poor prognosis, particularly those who received corticosteroids. The method appeared to be a valuable tool in monitoring disease activity and prognosis, and in evaluating the efficacy of corticosteroid treatment. The role of HBsAg-CICs in the pathogenesis of liver damage and clearance of circulating HBsAg is discussed.  相似文献   

5.
Cell mediated and humoral immunity to hepatitis B surface antigen (HBsAg) was studied in nine asymptomatic HBsAg carriers, nine patients with natural acquired immunity to HB infection and nine HB-susceptible donors. Peripheral T and B lymphocytes from all asymptomatic HBsAg carriers and all HB-immune donors studied were specifically induced into proliferation and anti-HBs secretion when stimulated with low doses of HBsAg (2-30 ng antigen protein/ml) in vitro. This activation was achieved by mixing purified B and/or T cells with optimal concentrations of autologous monocytic cells. T and B cells from the HB-susceptible donors were non-responsive under identical culture conditions. These data do neither substantiate the existence of a qualitative defect in T cell function, nor the absence of circulatory B cells capable of synthesizing anti-HBs in vitro in asymptomatic HBsAg carriers. Thus, the inability to mount a satisfactory antibody response to HBsAg in vivo might be a consequence of altered immune responsiveness to this antigen, which may be a relevant factor in the pathogenesis of asymptomatic HBsAg carriership.  相似文献   

6.
Physicochemical studies of hepatitis B e antigen (HBeAg) revealed a clear cut difference between e1 and e2 antigen. The e1 antigen was found to have a MW of Ca 150,000 and a pI of 6.4-7.2, whereas both the MW and pI of the e2 antigen were heterogeneous depending upon the source of serum. Sera obtained from asymptomatic carriers were characterized by low titers of HBs antigen, HBc antigen and DNA polymerase and contained e2 antigen of larger molecular weight (200,000-300,000) with a narrow distribution range and a pI of 4.8 to 5.2 (type 1). On the other hand, the sera from patients in a hemodialysis unit who were HBs antigen carriers and had high titers of HBs antigen, HBc antigen and DNA polymerase contained e2 antigen of heterogeneous distribution in MW (from 300,000 to 70,000) and pI (type 2 and 3). The e2 antigen obtained from the higher MW type 3 serum had lower isoelectric points (pI 4.5 to 5.2) as was the case with e2 antigen obtained from asymptomatic carriers whereas relatively wide range of isoelectric points (pI 5.1 to 8.2) was found with the lower molecular weight e2 antigen.  相似文献   

7.
The presence of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), the nature of T-cell function, and specific cell-mediated immunity to HBsAg were determined and evaluated serially in groups of subjects with chronic HBsAg carrier states and in seronegative controls. The techniques of in vitro lymphocyte transformation, spontaneous rosette formation, radioimmunoassay, reverse passive hemagglutination, passive hemagglutination, rheophoresis, and liver function tests were employed for these studies. For the lymphocyte transformation assay, multiple concentrations of phytohemagglutinin and purified HBsAg were used as stimulants. Cell-mediated immunity to HBsAg was detectable in 50% of the chronic HBsAg carriers (responders) at one or more concentrations of HBsAg. The remaining carriers (nonresponders) and controls failed to manifest HBsAg-specific lymphocyte transformation activity. The profile of the responders was characterized by elevated serum glutamic pyruvic transaminase levels, the presence of anti-HBe, high HBsAg titers, and the conspicuous absence of HBeAg in the serum. The nonresponders were characterized by normal serum glutamic pyruvic transaminase levels, the presence of HBeAg and anti-HBe, and lower HBsAg titers. These observations demonstrate the presence of specific cell-mediated immunity to HBsAg in chronic HBsAg carriers who manifest biochemical evidence of liver disease.  相似文献   

8.
The author evaluated the risk of VHB infection in families of carriers of HBsAg from the prevalence of the surface antigen and VHB morbidity in members of the family. The risk is 9.4%. It was revealed that a HBsAg carrier acted as a source of infection in 7.2% of all investigated cases of VHB. Part of the assembled sera of HBsAg carriers was examined for the presence of HBsAg and anti-HBe. A high infectiousness corresponding to the finding of HBsAg was detected in 27% of the examined subjects, most frequently in the group aged 0-9 years. Anti-HBe antibodies were detected in 69.3% of the examined subjects. The presence of HBsAg in carriers of the surface antigen of VHB helps to differentiate highly infectious subjects and to define adequate provisions in the focus of infection.  相似文献   

9.
Peripheral T lymphocytes from asymptomatic HBsAg carriers and hepatitis B (HB) immune (naturally acquired or vaccine induced) donors were induced into interleukin-2 (IL-2) secretion by plasma-derived HBsAg and the translational products of the S- and pre-S2+S gene of HB virus (HBV) in vitro. Biphasic time courses of IL-2 secretion were obtained for all donors tested. The first peak seemed to be mitogenically induced, as it was demonstrated in T cell cultures from asymptomatic HBsAg carrier, HB-immune donors as well as HB-susceptible controls and exhibited similar kinetics to that of the mitogen phytohaemagglutinin (PHA) induced IL-2 secretion. The mitogenically induced IL-2 secretion was prompt in T cell cultures from asymptomatic HBsAg carriers compared with HB-immune and HB-susceptible donors, and significantly higher after stimulation with high (100-1,000 ng/ml) compared with low (0.1-1.0 ng/ml) concentrations of HBsAg, indicating that T lymphocytes from asymptomatic HBsAg carriers are mitogenically pre-activated by circulatory HBsAg in high concentrations in vivo. In contrast, the second peak obtained after 4-7 days of antigen stimulation was antigen-specifically induced as it was not registered in control culture supernatants from HB-susceptible individuals. T cells from six out of seven asymptomatic HBsAg carriers exhibited reduced responsiveness to the translational product of the S-gene of HBV, whereas T cells from HB-immune donors responded equally well to pre-S2 containing and non-containing HBsAg preparations. An HBsAg-induced mitogenic T cell activation and aberrant T cell sensitization towards S-gene-encoded determinants may result in altered immunoregulatory functions within the T cell compartment, with consequences for the development of an adequate antibody response to HBsAg in asymptomatic HBsAg carriers.  相似文献   

10.
Sera from 20 Chinese patients with chronic hepatitis B were examined for hepatitis B e antigen and hepatitis B virus (HBV) DNA. There was considerable discordance with HBV DNA not being detectable in 10 out of 13 (77%) patients who were hepatitis B e antigen positive. Further testing for anti-HBe and HBV-DNA polymerase activity confirmed the results. Possible reasons for this discordance are discussed but neither hepatitis D (delta) infection nor the acquired immunodeficiency syndrome (AIDS) could be implicated.  相似文献   

11.
The immune system of 69 asymptomatic HBsAg carriers with normal liver function tests was evaluated. B cell function, as documented by serum immunoglobulin levels, number of mouse rosette-forming lymphocytes and lymphocyte reactivity to staphylococcal protein A, was intact. On the other hand, T cell function was markedly impaired. This was manifested by a significant decrease in E rosette-forming lymphocytes, an increase in stable rosette-forming cells and decreased reactivity to phytohaemagglutinin and concanavalin A. These data rule out the possibility that the immunological aberrations associated with hepatitis B infection are secondary to liver injury. The abnormal immune state either precedes the viral infection, thus predisposing to the acquisition of a carrier state or, alternatively, is a direct result of the infection.  相似文献   

12.
The presence of hepatitis B virus (HBV) DNA in sera of 56 chronic carriers of hepatitis B surface antigen (HBsAg) was determined by three methods: the Abbott hybridization assay, the polymerase chain reaction (PCR) followed by gel electrophoresis and UV visualization (PCR-GE), and PCR followed by DNA enzyme immunoassay (PCR-DEIA). HBV DNA was detected in four samples positive for hepatitis Be antigen (HBeAg) by all methods used. Both PCR-GE and PCR-DEIA detected viraemia in two anti-HBe, anti-HBc IgM positive samples. In the group of 50 anti-HBe positive samples the sensitivity of the three methods was 10 %, 24 % and 32 %, respectively. PCR-GE and PCR-DEIA results correlated well with the patients' clinical status; of 20 patients with elevated ALT levels, 12 (60 %) were found to be positive in the PCR-GE and another 2 were found to be positive in the PCR-DEIA (70 %). These data indicate that PCR-DEIA is the most sensitive method for detection of HBV DNA. This method can be relatively easily applied in the clinical laboratory for monitoring the progression of disease and/or interferon therapy in patients with chronic hepatitis B.  相似文献   

13.
The proteins of viral envelope, encoded by the pre-S1 region of HBV-DNA, were measured quantitatively with enzyme immunoassay using monoclonal antibodies directed to pre-S1 epitope and correlated with the expression of pre-S2 region encoded epitope and other HBV markers. In acute HBV infection, both pre-S encoded proteins were detected in sera along with markers of viral replication and disappeared shortly before complete virus clearance while high HBsAg titers were still present. Pre-S1 antigen was present in most (95.5%) symptomatic and asymptomatic chronic HBsAg carriers. There was no correlation between the presence of pre-S1 and HBeAg or HBV-DNA in serum: 73% of sera with pre-S1 determinants were anti-HBe positive, and only 25.4% were positive for HBV-DNA. Most pre-S1 activity in sera of viremic carriers was detected in fractions of sucrose gradient containing subviral 22-nm particles, and much less in those containing infectious virions. In asymptomatic, nonviremic HBsAg carriers, pre-S1 was located only on subviral 22-nm forms. Pre-S1 positive particles had no accessible pre-S2 epitope, which is recognized specifically by monoclonal anti-pre-S2 (F124) antibody. These results show that the synthesis of the large protein of HBV envelope may occur also in the absence of active viral replication, and in these cases pre-S1 encoded sequences are on subviral particles of HBsAg. Therefore, pre-S1 is not a serologic marker of infectious virus. Disappearance of pre-S1 epitopes on HBsAg occurs only before complete clearance of the virus, and this may have potential prognostic relevance.  相似文献   

14.
An important system of infectiousness in HBsAg positive subjects is HBeAg. The authors examined a total of 145 HBeAg carriers for the presence of HBeAg, using the RIA method. In 88 subjects on records of the District Hygiene Station on account of positive HBsAg HBeAg was present in 25%. In the group of 26 patients included in a regular haemodialyzation programme 92.3% were HBeAg positive. Another group comprises 31 inmates of a social care institute where HBeAg was revealed in 22.58%. Viral hepatitis B in the case-history was recorded in HBeAg positive subjects in 100% of dialyzed patients, in 56.25% of subjects on records of the District Hygiene Station and in 14.28% of the children in social care institutions. The authors discuss the problem of the epidemiological impact of HBeAg positive subjects as possible sources of viral hepatitis type B. Despite the limited importance of HBeAg examinations for the unequivocal assessment of infectiousness of HBsAg/HBeAg positive subjects the authors assume that general availability of HBeAg examination will be a valuable contribution to epidemiological practice.  相似文献   

15.
Asymptomatic liver disease in hepatitis B antigen carriers   总被引:6,自引:5,他引:1       下载免费PDF全文
Thirty-four healthy blood donors, found to be persistent HBAg carriers, have been investigated by means of serial liver function tests, bromsulphthalein (BSP) retention, and liver biopsy. Thirty-one of the donors had histological abnormalities including one with cirrhosis, three with chronic aggressive hepatitis, and 11 with chronic persistent hepatitis. In 13 biopsies there were focal areas of necrosis in the liver parenchyma. Serial liver function tests revealed abnormalities in each of the donors with cirrhosis or with chronic aggressive hepatitis, in seven of the 11 donors with chronic persistent hepatitis, and in seven of the 13 with focal parenchymal necrosis. The degree of BSP retention was greatest (>11%) in the donors with chronic aggressive hepatitis. The severity of the histological changes was related neither to the titre of the antigen in the serum nor to the presence of autoantibodies.  相似文献   

16.
17.
乙肝表面抗原突变体的表达及其初步应用   总被引:1,自引:0,他引:1  
目的:构建和表达乙肝表面抗原(HBsAg)突变体用于HBsAg抗原性的深入研究。方法:利用定点突变技术构建HBsAg突变体,然后转化毕赤酵母GS115,菌落PCR、高浓度Zeocin抗性筛选鉴定转化子,表达产物经SDS—PAGE分析和Western blot分析,利用AxSYM HBsAg V2(Abbott)酶免试剂盒检测重组表面抗原的活性。结果:通过序列分析确定突变体构建成功,SDS—PAGE显示突变体能在毕赤酵母中有效表达,在Western blot试验中HBsAg突变体被特异性多克隆抗体识别,相对分子质量(Mr)约为38000,AxSYM试剂盒检测结果表明HBsAg突变体具有一定生物活性。结论:利用毕赤酵母表达系统高效表达出具有一定免疫反应性的HBsAg突变体。对于目前市售试剂盒的质量控制和临床应用有较高的实用价值。  相似文献   

18.
Quantitative determination of hepatitis B virus (HBV) DNA concentration is the most important measure for an estimation of the infectivity of an HBV positive health care worker and the basis for the decision whether he or she is allowed to perform exposure prone procedures. Thus questions are raised on how reliable quantitative HBV DNA assays are, and how stable is the HBV DNA concentration is in a healthy chronic HBV carrier. Therefore, in the present study two commercially available quantitative HBV DNA assays, the Amplicor HBV Monitor and the HBV Test Hybrid Capture II, and an "in house" quantitative HBV TaqMan PCR, analysing 101 sera of HBsAg positive patients for HBV DNA were compared. In addition, HBV DNA concentrations were followed in 14 healthy chronic carriers for up to 6 years. Despite a good overall correlation between the three tests considerable differences were found for the results of individual sera. Fifty-one percent of sera showed differences within one order of magnitude, 45% differed by a factor above 10 and 4% even by a factor of 100 and higher. The follow-up of the HBV DNA concentrations in 14 carriers showed in 7 carriers a rather stable course with variations within one order of magnitude, whereas in the other half the DNA concentrations fluctuated by factors between 10(2) and 10(6) over the observation period. Thus, viral load determinations in health care workers have to be interpreted with some caution, especially when they are the basis of far-reaching decisions.  相似文献   

19.
Light and electron microscope finding from a liver of a chronic carrier of hepatitis B surface antigen (HBsAg) showed small lymphocytes and macrophages in close contact with liver cells, partial lysis of variable degrees, lytic necrosis, and the complete loss of a few hepatocytes with HBsAg in the cytoplasm. On the basis of these findings, together with the results from immunofluorescence study, the pathogenesis of hepatitis B is discussed, with emphasis on the importance of host cellular immune response. The cytopathic and cytolytic activities of immunologically activated T lymphocytes against liver cells that have antigenic targets associated with HBsAg at their surface and in the cytoplasm are discussed.  相似文献   

20.
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