Retrospective analysis of non-A-E hepatitis: possible role of hepatitis B and C virus infection

In an effort to determine the cause of non-A-E hepatitis, a retrospective study was undertaken on a group of patients with hepatitis but without serological infection markers of hepatitis viruses A-E. A total of 60 patients admitted to Beijing Ditan Hospital during the period of September 1997 and September 1999 were chosen for this study. These patients were diagnosed as either acute or chronic hepatitis, but no serological markers of hepatitis viruses A-E were detected. Since TT virus (TTV), human parvovirus B19 (B19), SEN virus (SENV), and GB virus C/HGV were reported to be associated with hepatitis, attempts were made to detect the presence of these viruses in the sera of patients with non-A-E hepatitis by a nested polymerase chain reaction (nPCR) method. Also, more sensitive nPCR and RT-nPCR methods were used to determine HBV DNA and HCV RNA in these patients. Results derived from these analyses demonstrate that HBV DNA was detected in most of these patients (47/60, 78.3%), suggesting that HBV infection played a major role in occult non-A-E hepatitis and detection of HBV DNA by more sensitive PCR methods such as nPCR should be considered for diagnosis of HBV infection. In addition, HCV RNA was detected in three (5%) of these patients. However, GBV-C (HGV) RNA was not detected, and TTV, B19, and SENV appear not to be associated with non-A-E hepatitis, as the prevalence rates of these viruses in patients with non-A-E hepatitis were similar to those in patients with viral hepatitis A-E. The results from this study indicate that co-infection of TTV or B19 with HBV did not increase the severity of the disease.     

Field evaluation of the efficacy and immunogenicity of recombinant hepatitis B vaccine without HBIG in newborn Vietnamese infants

A study involving more than 2,000 infants was conducted in Vietnam to assess the field effectiveness and immunogenicity of recombinant hepatitis B vaccine given at birth, 1 month, 2 months, without concomitant hepatitis B immune globulin (HBIG). All received a 5 microg dose of H-B-VAX II at birth. Infants born to non-carrier mothers (Group 1; N = 1798) then received 2.5 microg doses at 1 and 2 months of age, while infants of HBeAg-negative (Group 2; N = 125) or HBeAg-positive (Group 3; N = 88) carrier mothers received 5 microg doses. No Group 1 or 2 vaccinees were infected. In Group 3, 12 (14.6%) of 82 infants did become infected (estimated efficacy 84%). 98.0-98.6% of uninfected infants who were tested for anti-HBs developed a seroprotective concentration > or = 10 IU/L. In hyperendemic Vietnam, where routine maternal screening and passive-active prophylaxis of high-risk infants with vaccine plus HBIG is not feasible, administration of vaccine alone to all newborns may control effectively HBV infection.     

Natural seroconversion from hepatitis Be antigen to antibody among hepatitis B virus carriers in Okinawa Islands

In the Okinawa Islands, the great majority of hepatitis B surface antigen (HBsAg) carriers have already acquired antibody to hepatitis Be antigen (anti-HBe) by the age of 30 years (preliminary cross-sectional data). To elucidate natural seroconversion from hepatitis Be antigen (HBeAg) to anti-HBe among HBsAg carriers found in the islands of Okinawa Prefecture, 34 HBeAg-positive HBsAg carriers were followed for 1-6 years with serial measurements of aminotransferase levels, HBeAg, and anti-HBe. The 34 subjects included 24 patients with chronic hepatitis (group 1) and ten asymptomatic HBsAg carriers (group 2). During the follow-up period, HBeAg disappeared from 14 subjects in group 1 with the cumulative clearance rate of HBeAg of 56.3% within the first 2 years and with 10 of the 14 subsequently developing anti-HBe. Moreover, the aminotransferases in 12 of the 14 spontaneously seroconverted fell into the normal range. The annual clearance rates of HBeAg among group 1 and group 2 were 25.6% and 9.3%, respectively. The tendency for early disappearance of HBeAg during a carrier's life time or in the course of chronic hepatitis may lead to the low death rate from hepatocellular carcinoma (HCC) particularly HCC associated with hepatitis B virus infection in this area.     

HBV重组抗原表位抗原性的研究

目的 在外源抗原表位表达载体系统中构建并表达HBV抗原表位,并对其抗原性进行研究.方法 人工合成编码HBV "a"抗原决定簇表位中24个氨基酸(S124-147)的寡核苷酸序列,克隆入外源抗原表位表达载体系统FHV-RNA2-I3位点,构建重组质粒,在原核pET系统(BL21细胞)中表达.以表达产物为包被抗原对其抗原性进行研究.结果 嵌和蛋白与抗-HBs血清可发生特异性结合反应.结论 在外源抗原表位表达系统中表达的HBV抗原表位具有良好的抗原性.     

Viral determinants and host immune responses in the pathogenesis of HBV infection

Hepatitis B virus (HBV) is a virus that infects about 350,000,000 people worldwide with a clinical spectrum of acute hepatitis, the healthy carrier state, cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is the result of complicated viral-host interactions. As in other infections with non-cythopatic viruses, the immune response is thought to play a crucial role in disease pathogenesis but there is increasing evidence that a variety of viral mechanisms, some depending on the function of virally encoded proteins, have a profound impact on the infected hepatocytes, the liver microenvironment, and host anti-viral responses. Indeed, the virus has evolved multiple mechanisms to ensure its success in infecting a susceptible host. The essential aspects of the life cycle of HBV and the host immune response are reviewed and recent new developments in the molecular virology of HBV, including experimental animal models, in the role of accessory viral proteins in disease pathogenesis and HCC development and in the characterisation of the T cell response in the control of HBV infection, are highlighted.     

Hepatitis B surface antigen particles of subtypes adw and adr, and compound subtype (adwr) in symptom-free carriers in Japan.

Of sera from 1,878 Japanese blood donors who carried hepatitis B surface antigen (HBsAg), 420 were subtyped as adw (22.4%) and 1,443 as adr (76.8%); only 15 (0.8%) contained HBsAg of subtype ayw or ayr. Sera with HBsAg/adr had higher HBsAg titres than those with HBsAg/adw (geometric mean of haemagglutination titre: 10.1 +/- 2.4 vs. 9.7 +/- 2.4, p less than 0.01), and a higher prevalence of hepatitis B e antigen (24% vs. 13%, p less than 0.001). Carriers of HBsAg/adr progressively predominated over those of HBsAg/adw with increasing age. Of sera from 1,863 carriers of HBsAg/adw or HBsAg/adr, 182 (9.8%) contained HBsAg particles with both subtypic determinants in the w/r allele. The presence of w and r determinants on the same particles was ascertained by sandwiching them between monoclonal antibody with the specificity for w and that with the specificity for r. HBsAg particles of compound subtype (adwr) were found more often in sera with hepatitis B e antigen than those without it (145/403 [36.0%] vs. 37/1,460 [2.5%], p less than 0.001). Sera with HBsAg/adwr particles had HBsAg titres higher than those without them (12.4 +/- 1.9 vs. 9.7 +/- 2.3, p less than 0.001). HBsAg/adwr particles arise from phenotypic mixing of the S-gene product of wild-type virus and that of mutants with point mutations for subtypic changes. The results obtained indicated that HBV strains of subtype adr have a higher replicative activity than those of adw, and suggested that mutations in the S gene for subtypic changes would be associated with an active replication of hepatitis B virus.     

Hepatitis B virus transmission in Brazilian hemodialysis units: serological and molecular follow-up

A serological and molecular study of hepatitis B virus (HBV) infection was carried out in dialysis units in Central Brazil. Between 1995 and 1999, serum samples from all HBsAg-positive hemodialysis patients (n = 43) were tested for HBeAg/anti-HBe and subtyping by monoclonal ELISA. HBV DNA was detected by PCR and positive samples were genotyped by restriction fragment polymorphism pattern (RFLP) methodology. TheHBsAg prevalence declined in this population during the survey period (12-5.8%). HBeAg and anti-HBe were detected in 23 (53.5%) and 18 (41.9%) sera, respectively. Thirty-six samples could be HBsAg subtyped: 21 were subtype ayw(3), 14 belonged to adw(2) and one was identified as adw(4). HBV DNA was present in 30 serum samples. Of these, 20 (66.7%) were genotype D, 9 (30%) genotype A, and 1 (3.3%) genotype F. In addition, the RFLP pattern could be determined in samples from 18/20 genotype D patients: D3 (10 strains), D7 (7 strains) and D4 (1 strain); from 8/9 genotype A patients: A1 (6 strains) and A3 (2 strains); and from the patient infected with genotype F: F1. Patterns D3 and D7 were associated closely with HBV infection in the two largest hemodialysis units studied. These findings confirm the value of the RFLP method as an effective molecular epidemiological tool for elucidating HBV transmission in hemodialysis units.     

Cloning and expression of surface antigens from occult chronic hepatitis B virus infections and their recognition by commercial detection assays

Occult hepatitis B virus (HBV) infections show little or no serological markers of viral infection, including the absence of hepatitis B surface antigen (HBsAg) which is the main marker of ongoing HBV infection. Such infections can be important in the context of blood and/or organ donations. To study whether mutations contribute to HBsAg seronegativity, S gene sequences from such patients were amplified and cloned. Sequencing revealed 12 clones from seven different patients which contained potentially important mutations. The sequences were subcloned into an expression vector and mutant HBsAgs were expressed in cell culture. The capacity of three HBsAg detection assays to recognise the mutant HBsAgs was studied. Three categories were found: mutant HBsAgs that are not recognised by the assays, those that are recognised as well as wild-type (WT) antigen and an intermediate category where detection of the mutant HBsAgs is reduced with respect to WT. Most of the isolates fall into the second category. Mutations can therefore contribute to HBsAg seronegativity in occult HBV infections, but in most cases the explanation is probably the low level of viral replication.     

重组质粒pcDNA3.1IL-2/Fc对HBV preS2S DNA疫苗免疫作用的影响

目的 探讨IL-2/Fc融合表达后对HBVpreS2S基因疫苗诱导免疫反应的佐剂效应.方法 采用HBV preS2S DNA疫苗作为基础免疫,重组质粒pcDNA3.1IL-2/Fc作为佐剂加强免疫BALB/c小鼠,采用0、2、4周的方案接种,检测各次接种后抗体水平.初次免疫后7周,测定免疫脾细胞的杀伤活性、增殖活性和细胞因子的分泌水平.结果 pcDNA3.1IL-2/Fc作为佐剂在HBV preS2S注射3 d后免疫组小鼠抗体滴度、免疫脾细胞的杀伤活性和增殖活性、TH1型细胞因子的分泌水平,均比各对照组明显增强.结论 IL-2/Fc是有效的HBV preS2S DNA疫苗佐剂之一.