Hepatitis B surface antigen carrier state in neonates. Prophylaxis with large doses of conventional immune human serum globulin

Acute type B viral hepatitis developed near the term of pregnancy in seven women. All had signs of acute hepatitis at delivery, and hepatitis B surface antigenemia persisted two to four weeks after delivery. Two milliliters of conventional immune human serum globulin was administered to the neonates within a week of birth, after preexisting type B viral hepatitis infection was excluded. The antibody against hepatitis B surface antigen (anti-HBs) content of two of the administered batches of immune human serum globulin was 1:32 and 1:64. None of the babies became hepatitis B surface antigen carriers, and anti-HBs developed without obvious clinical hepatitis in one baby. Conventional immune human serum globulin in larger doses may be a relatively safe and effective prophylaxis against the development of hepatitis B surface antigen carrier state even if the anti-HBs content in the administered dose is relatively small.     

Hepatitis B surface antigen and antibody in asymptomatic blood donors

Various flavoring agents were evaluated as to their ability to improve the taste acceptability of Vivovnex-HN, a potent oral hyperalimentation diet. Several imitation flavors were incorporated into the Vivonex-HN powder in different concentrations with and without an artificial sweetener. The mixtures were rated by a taste panel. Among the unsweetened flavors, spray-dried orange juice, Sealva imitation mint No.381 and cherry mint imitation appeared to be the most acceptable flavors. Among the individual flavors sweetened with 0.025% sodium saccharin, rum, strawberry and raspberry proved to be the most acceptable. Among all of the formulations studied, a combination of rum, strawberry and raspberry with 0.025% sodium saccharin was found to be optimal.     

Hepatitis B virus surface antigen binds to apolipoprotein H

We have previously demonstrated that a plasma membrane-enriched fraction isolated from human liver is capable of binding recombinant hepatitis B surface antigen (rHBsAg) (P. Pontisso, M. A. Petit, M. Bankowski, and M. E. Peeples, J. Virol. 63:1981-1988, 1989). In this study we have separated the plasma membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and used a ligand-blotting technique to identify a 46-kDa rHBsAg-binding protein. This protein could be removed from the membranes with a weakly acidic buffer, implying that it is peripherally bound. Examination of human serum revealed that the 46-kDa binding protein is a serum protein. Isolation of plasma lipoproteins revealed that the binding protein is in part associated with chylomicrons and high-density lipoproteins, both of which are targeted to the hepatocyte during the normal course of lipid metabolism. The binding protein was identified as apolipoprotein H (apo H), also known as beta 2-glycoprotein I, on the basis of copurification of the rHBsAg-binding activity with the apo H protein and the ability of cDNA-expressed apo H to bind rHBsAg. Serum-derived HBsAg also binds to apo H, indicating that binding is not unique to rHBsAg. Binding is saturable, requires only the small S protein of rHBsAg, and is inhibited by excess rHBsAg, antibodies to HBsAg, and antibodies to apo H. The binding activity of apo H is destroyed upon reduction, indicating that 1 or more of its 22 disulfide bonds are required for interaction with rHBsAg. The possibility that an interaction between hepatitis B virus particles and lipoprotein particles may facilitate entry of the virus into hepatocytes is discussed.     

Adoption and chronic hepatitis B carrier state

AIM: Because there are few adoptable children in France, parents, for the last 20 years, have turned to international adoption. Alerted by the generally poor health of these children, we paid particular attention to their health problems and especially to infection by hepatitis B virus (HBV). POPULATION AND METHODS: The 60 internationally-adopted children seen from June 1993 to June 1997 were included in this study. All had hemogram and serum iron dosage, and search for intestinal parasites and tuberculosis was performed in each child, as were HBs antigen and HBs antibody screening. When HBs antigen was positive, HBe antigen and antibodies, HBV DNA and hepatitis C and delta serology were also studied. RESULTS: Six out of the 60 children were HBV chronic carriers. The six presented HBs antigen and five out of the six presented viral DNA. One child was co-infected with delta virus. Serum aminotransferase was normal in three children and increased in the three others. DISCUSSION: Some internationally adopted children are exposed to chronic infection by HBV. This concerns children coming from countries known for the high frequency of the disease, but also children with long stay in Eastern European nurseries. Chronic HBV carriage puts the child, as well as the family and other children in institutions and/or schools at risk, thus necessitating preventive measures.     

Lack of ultrasonographic evidence for severe hepatosplenic morbidity in schistosomiasis mansoni in Mali

The inhabitants of four villages endemic for Schistosoma mansoni in central Mali (n = 1,106 of both sexes, age range 2-80 years) and of two nonendemic villages in another part of the country were examined parasitologically and ultrasonographically to establish the prevalence of periportal liver fibrosis (PF) and other features of hepatosplenic schistosomiasis. The prevalence of S. mansoni infection ranged from 36% to 93% in the endemic villages. A severe infection (> 400 eggs/g of stool) was found in 16% of the infected individuals. No case of grade III PF (echogenic bands usually > 10 mm in diameter around the central part and major branches of the portal vein and streak-like fibrous bands that extended into the periphery of the liver) and only eight cases of grade II PF (echogenic bands usually > 10 mm in diameter around the central part and major branches of the portal vein) were found; no other signs of severe hepatosplenic disease were encountered. However, grade I PF (echogenic bands usually > 4 mm in diameter that were best visible in the area of the portal vein bifurcation and gall bladder neck) was detected in 21% of all individuals, mainly in adults. In the nonendemic villages, the prevalence of grade I PF in adults was 9%. Generally, there was no significant correlation between the grade of PF and S. mansoni egg output. In one village with a high endemicity level, however, the prevalence of grade PF I increased with the intensity of infection. Morphometric data revealed no significant influence of S. mansoni infection on portal vein stem diameter and spleen size.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proteins of hepatitis B surface antigen

Purified 22-nm forms of hepatitis B surface antigen (Hbsag) representing the three major antigenic subtypes (adw, ayw, and adr) were analyzed for their constituent polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No consistent difference in either the number or relative distributions of the polypeptides was observed for the various subtypes. Seven polypeptides were designated as P-1 through P-7 in order of their decreasing mobilities. By comparison with protein standards, their molecular weights were estimated as 23, 29.5, 36, 41.5, 53.5, 72, and 97 thousand. The P-1 and P-2 components represented the major polypeptides; P-2 and P-5 might by glycoproteins, based on their reaction with periodic acid-Shiff reagent. Each polypeptide contains cysteine residues. HBSAg was radiolabeled with 3H or 14C by reductive methylation or iodinated with 125I by the chloramine-T or lactoperoxidase procedures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of labeled HBSAg yielded patterns identical to those obtained with protein stain. Comparison of HBSAg labeled by the chloramine-T and lactoperoxide procedures indicated that there was no distinction between internal or external components within the 22-nm structure.     

Clinical aspects and imaging patterns with ultrasonography and endoscopy in hepatosplenic schistosomiasis in Uganda

In patients with hepato-splenic schistosomiasis, a close relationship between the grade of periportal fibrosis and portal vein diameter, spleen size and presence of oesophageal varices and their grade was found.     

False negative hepatitis B surface antigen detection in dialysis patients due to excess surface antigen: postzone phenomenon

Renal dialysis patients are well known to have a high incidence of hepatitis B carrier state. In studying a group of 63 long-term dialysis patients, 10 were found to be positive for hepatitis B surface antigen by radioimmunoassay (RIA). Surprisingly, however, only three of these RIA positive patients were positive by counter immunoelectrophoresis (CIEP). The discrepancy could not be accounted for by the difference in sensitivity of the two methods. The cause for the negative reactions by CIEP in seven patients was found to be the marked excess surface antigen in these sera which produced false negative results by the postzone phenomenon. After dilution all seven sera were positive by CIEP, requiring a dilution up to 1/20 to produce a positive result. Also, all seven sera were positive by the less sensitive Ouchterlony double diffusion.     

Aggregation of recombinant hepatitis B surface antigen in Pichia pastoris

The combination of immunoaffinity and size-exclusion chromatography (SEC) is a powerful tool to analyze multiprotein particle assembly. This approach was used to investigate the source of aggregation of recombinant hepatitis B surface antigen (HBsAg) detected in purified material. As HBsAg aggregation does not originate in the stresses, such as the concentration of HBsAg solutions, temperature and chaotropic agents, it is less probable that the HBsAg aggregate is produced during the process. To test whether aggregation takes place in vivo, crude yeast extract containing the expressed HBsAg was fractioned on a Sephacryl S-400 column just after cell disruption, and each fraction immunopurified individually. As a result, the HBsAg aggregate was isolated from a fraction corresponding to the elution of large particle aggregates only, not native HBsAg particles. It was biologically active, which demonstrates aggregate formation by specific assembly of partially or wholly folded HBsAg intermediates.     

Examination of the polypeptides of hepatitis B surface antigen

When the polypeptides of hepatitis B surface antigen were examined by SDS-polyacrylamide gel electrophoresis under a variety of conditions, anomalous results were found to be due to (i) variable and at times incomplete dissociation of polypeptides after boiling with 1% SDS and reducing agent, (ii) reaggregation of solubilized material under certain electrophoretic conditions and during laboratory manipulations, and (iii) the variable presence of additional components in hepatitis B surface antigen prepared from certain individual donors. When these factors were taken into account, two major components were consistently identified by discontinuous buffer polyacrylamide gel electrophoresis, of apparent mol. wt. 60000 to 70000 and 12000 to 14000. However, in view of the demonstrated limitations of this technique in examining HBsAg polypeptides, alternative methods are necessary to confirm the true mol. wt. of the unique virus-specified amino acid sequence present.     

High prevalence of e antigen among healthy blood donors carrying hepatitis B surface antigen in Japan

Hepatitis B surface antigen (HBsAg) was detected by an immune adherence haemagglutination method in the serum samples of 292 voluntary, apparently healthy blood donors at four regional blood centres in Japan. Their serum samples were concentrated 3-fold and tested for e antigen (e Ag) and antibody to e (anti-e) by immunodiffusion. The e Ag was found in 41 samples (14.0%) and anti-e in 57 (18.6%). When 100 randomly selected serum samples containing HBsAg were tested as they were (unconcentrated), and at 3- and 5-fold concentrations, e Ag was detected in 3, 16 and 27, respectively, and anti-e in 10, 21 and 26. Subtypes of HBsAg were similar in carriers with e Ag and with anti-e. There is a high prevalence of e Ag in healthy individuals in Japan. There are also high rates of vertical transmission of hepatitis B virus from mothers to children, as well as a high incidence in the past of post-transfusion hepatitis. This is further evidence that e antigen is a marker for the infectivity of hepatitis B virus in carriers.     

A humanized antibody with specificity for hepatitis B surface antigen

A murine monoclonal antibody H67 was characterized for the binding specificity, which showed that H67 recognizes a disulfide-bond-dependent conformational epitope of common a antigenic determinant on the hepatitis B surface antigen. The result suggested that this antibody may have the potential of replacing hepatitis B immune globulin in the prevention of hepatitis B virus (HBV) infection. Therefore, we have constructed the humanized antibody HuS10 by grafting the complementarity determining regions and some framework amino acid residues of H67 onto the most homologous human antibody variable regions, 21/28 for heavy chain variable region and B1 and J kappa 2 for light chain variable region, followed by combining with human constant regions C gamma 1 and C kappa. The affinity of the HuS10 was the same as that of the H67, 8 x 10(8) x 10(8)M-1, and the HuS10 neutralized the in vitro infection of adult human hepatocyte primary culture by adr or ayw subtype of HBV. The neutralization assay showed that the HuS10 had approximately 2,000-times higher specific activity than commercially available polyclonal HBIG. These results suggest that the humanized antibody will be useful in the prevention or treatment of HBV infection.     

The prevalence of hepatitis B surface antigen in commercially prepared plasma products

Commercially available lots of plasma derivatives prepared between 1957 and 1975 were tested for hepatitis B surface antigen (HBsAg) by radioimmunoassay. In all, 69 per cent of lots of plasma protein fraction, 40 per cent of factor IX concentrate, 20 per cent of normal serum albumin, 13 per cent of antihemophilic factor, 3 per cent of fibrinogen, and 0.7 per cent of immune serum globulin lots tested were HBsAg-positive. There was great variation in the prevalence of HBsAg-positive lots of each product among the different manufacturers, reflecting not only differences in methods of processing plasma, but also differences in donor populations. Those manufacturers relying upon volunteer donor plasma or placental source material demonstrated lower rates of HBsAg-positive lots of final products than those relying upon commercial donor plasma. There was a marked decrease in the prevalence of positive lots during the period 1971 to 1973, coincident with the onset of routine plasma donor screening for HBsAg. However, current requirements for plasma screening have not resulted in totally HBsAg-free plasma products. Use of more sensitive and more reliable tests for HBsAg will probably reduce contamination of plasma pools with HBsAg to undetectable levels. Despite HBsAg-status, however, the "high-risk" plasma products (fibrinogen, antihemophilic factor, factor IX concentrate) must still be considered capable of transmitting hepatitis and used only with the strictest indications.