Hepatitis B antigen: distribution of ad and ay subtypes in blood donors and hepatitis patients

Hepatitis B antigen (HBAg) from blood donors and patients with hepatitis was tested for ad and ay subspecificity by immunodiffusion in agarose. A total of 59 sera from blood donors and 81 sera from hepatitis patients were subtyped.Subtyping of HBAg from blood donors showed ad and ay subspecificity in 64.4 and 35.6% of cases respectively. Patients'' sera on the other hand showed HBAg with ad and ay subspecificity in 6 and 94% of cases respectively. Therefore, ad subtype was more frequently associated with blood donors whereas ay subtype was predominant among hepatitis patients. The relationship between clinical findings and HBAg subtype is also discussed.     

Hepatitis G virus (GBV-C) infection among Brazilian patients with chronic liver disease and blood donors

Background: The recently discovered hepatitis G virus (HGV) belongs, as hepatitis C virus (HCV), to the Flaviviridae family. HGV has been isolated from the serum of patients with non A-E hepatitis. However, the association of HGV with hepatitis is uncertain.Objective: To determine the HGV prevalence in blood donors and in patients with liver disease and to evaluate a possible correlation between HGV infection and liver disease.Study design: Sera from a total of 113 consecutive patients with chronic liver disease were submitted to a series of liver enzymes and function tests and analyzed for the presence of HBsAg, anti-HBs, anti-HBc, anti-HCV, HCV RNA and HGV RNA. Prevalence of HGV RNA was determined in a group of 87 blood donors.Results: Nine (10%) sera from blood donors and 15 (13%) sera from patients with chronic liver disease were HGV RNA positive. Some 28 (25%) patients were HCV RNA positive, with genotypes 1a, 1b and 3 present in 10, 12 and 5 patients, respectively. A total of 20 (18%) patients were HBsAg carriers. Five (4%) patients were double infected (one with HBV+HCV, one with HBV+HGV and three with HCV+HGV).Conclusion: The proportion (10%) of HGV-infected blood donors was very high when compared with other countries. The results did not allow to establish HGV as an etiologic agent for chronic liver disease. The parenteral route was the presumed means of HGV transmission for only one-third of the patients.     

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.     

基于UPLC-QTOFMS正、负离子模式对无偿献血者乙型肝炎表面抗原阳性血清代谢组学的研究

目的:基于超高效液相色谱-单四极杆飞行时间质谱(UPLC-QTOFMS)正、负离子模式探讨无偿献血者中乙型肝炎表面抗原阳性和乙型肝炎表面抗原阴性的血清代谢组学的差异,为乙型肝炎的诊断寻找潜在的血清生物标志物。方法:选取2017年10月~2018年1月在青海省血液中心检测的乙型肝炎表面抗原阳性57例(研究组)与同期无偿献血者乙型肝炎表面抗原阴性63例(对照组),利用UPLC-QTOFMS技术建立两组血清代谢指纹图谱,采用主成分分析(PCA)和偏最小二乘法-判别分析(PLS-DA)分析两组间有差异的小分子物质,确定与乙型肝炎相关的生物标志物,并分析相关代谢机制。结果:通过变量重要性投影、质谱鉴定和数据库检索筛选出8个潜在的生物标志物,分别为缬氨酸、胆碱、甘氨鹅去氧胆酸、肉毒碱、高丝氨酸、溶血磷脂酰胆碱、血清溶菌酶和花生四烯酸,涉及胆汁酸代谢、氨基酸代谢、磷脂代谢等。结论:无偿献血者中乙型肝炎表面抗原阳性和乙型肝炎表面抗原阴性的血清代谢物存在显著差异,差异代谢物的发现有助于寻找乙型肝炎的潜在生物标志物,为血液安全提供依据。     

Familial Clustering of Hepatitis B Antigen: A Study in Relatives of Patients with Liver Diseases and Hepatitis B Antigenaemia

Twelve of the 100 family contacts of 29 patients with transient and persistent hepatitis B antigenaemia were found to be positive for hepatitis B antigen (HBAg). No relation was found between familial clustering and the nature of liver disease or the duration of antigenaemia in the index cases.Eight affected relatives were apparently healthy carriers of HBAG, one had cirrhosis, and three (in the same family) developed acute viral hepatitis.The absence of parenteral exposure in the HBA,-positive family contacts and the identity in antigenic determinants d or y with those of the index cases, suggest a non-parenteral spread of HBAg in families of patients with HBAg-associated liver diseases.     

Cell-mediated and humoral immunity in HBS-Ag carriers]

The presence of HBs--Ag in the blood was established in 1.8% of practically healthy persons, in 29.7% of virus hepatitis patients and in 86.0% of serum hepatitis patients. The immunological study of clinically healthy HBs--Ag carriers revealed a statistically significant decrease in the number of T and B lymphocytes and an increased level of serum IgA, IgM and IgG in the blood. Among donors, 7.6% were found to have lymphocytes sensitized to HBs--Ag and 15.4% were found to have lymphocytes sensitized to liver antigen, while for HBs--Ag carriers these data were 62.5% and 50%, respectively.     

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.     

Hepatitis B antigenemia among blood donors: the changing scene.

For the period May 1973 to August 1974 inclusive, the mean prevalence of hepatitis B antigenemia (HBsAg) in all Canadian provinces (per 100,000 population) was, for "first-time" donors, 242 and, for "repeat" donors, 77. A modification of counterimmunoelectrophoresis was used in all 16 regional transfusion centres. The findings confirm the previously noted high prevalence for the Province of Québec and the continuing relatively high prevalence for Canada. The prevalence of HBsAg among donors could be lessened by institution of the following measures: development of a more effective technique for the screening of hepatitis carriers, study of nonparenterally transmitted hepatitis, better reporting of post-transfusion hepatitis, and greater discrimination in prescribing blood and blood components.     

Prediction of Clinical Outcomes in Hepatitis B E Antigen Negative Chronic Hepatitis B Patients with Elevated Hepatitis B Virus DNA Levels

Objectives

We investigated whether long-term clinical outcomes such as disease progression or inactive hepatitis B virus (HBV) carrier state can be predicted by baseline factors in hepatitis B e antigen (HBeAg)-negative HBV infected patients with an elevated viral load.

Methods

A retrospective cohort of 527 HBeAg-negative chronic HBV infected patients with an elevated viral load (HBV DNA ≥ 2,000 IU/ml) was assessed for disease progression defined by the development of hepatocellular carcinoma (HCC) or cirrhotic complication, as well as becoming an inactive carrier.

Results

During a median 3.6 years of follow-up, disease progression was detected in 46 patients (40 with HCC, 6 with cirrhotic complication), and 31 of 309 non-cirrhotic patients became inactive carriers. Older age, male gender, cirrhosis, high HBV DNA levels at baseline, and short antiviral therapy duration were independent risk factors for HCC. Low HBV DNA and quantitative hepatitis B surface antigen (qHBsAg) levels were independent predictors for becoming inactive carriers in patients without cirrhosis. In non-cirrhotic patients with both low qHBsAg and HBV DNA levels, the 5-year cumulative incidence of an inactive carrier was 39.8%, while that of disease progression was 1.6%.

Conclusion

HBeAg negative patients without cirrhosis can be closely monitored for becoming an inactive carrier when both HBV DNA and qHBsAg levels are low, as the risk of disease progression is low while incidence of an inactive carrier is high.     

Occurrence of non-A, non-B post-transfusion hepatitis in heart surgery. Prospective study on the value of the determination of serum alanine aminotransferase and detection of anti-HBc antibodies in blood donors

We studied a group of 64 patients undergoing cardiac surgery for the occurrence of post-transfusion hepatitis during a follow-up period of 5 months. They received blood units (packed red cells in saline-adenine-glucose medium and/or fresh frozen plasma exclusively) from 447 volunteer donors. Post-transfusion hepatitis was identified in 5 patients: 1 patient had cytomegalovirus hepatitis and the remaining 4 cases were defined, by exclusion, as non-A, non-B hepatitis (with prevalence and incidence rates of 80% and 6.25% respectively). We found no statistically significant differences between the numbers of transfused blood product units in patients who developed non-A, non-B hepatitis as compared to those who did not. Our analysis of the predictive effectiveness of alanine aminotransferase and anti-HBc antibodies screening in blood donors to prevent non-A, non-B post-transfusion hepatitis led to the following conclusions: we failed to confirm the association between anti-HBc in blood donors and enhanced risk of non-A, non-B hepatitis in recipients since no case developed among patients receiving blood products from anti-HBc positive donors. So, 20 donors (4.5%) would have been discarded without any reduction of the incidence of non-A, non-B hepatitis. we could not confirm nor exclude the possibility that screening donor blood for elevated alanine aminotransferase levels would have reduced the number of non-A, non-B hepatitis in recipients.     

Changes induced by Hepatitis Serum in Cultured Liver Cells

THE discovery of the relationship between the Australia (hepatitis-associated) antigen and serum hepatitis has provided a specific serological marker of infection for type B viral hepatitis. The precise biological nature of the Australia antigen remains uncertain and so far there has been no convincing demonstration of the successful infection of tissue culture preparations in spite of extensive efforts¹. We now report the nuclear involvement of cultured primary human embryo liver cells inoculated with the serum of a well-documented former blood donor (P. J. G.) whose blood had been implicated in the transmission of serum hepatitis in transfused recipients and had induced serum hepatitis in human volunteers. Australia antigen has been repeatedly demonstrated in the serum of this blood donor^1,2.     

A case of hepatitis B reactivation due to the hepatitis B virus escape mutant in a patient undergoing chemotherapy

A 62-year-old man had chronic hepatitis B virus (HBV) infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient’s virologic markers were positive for hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc), while antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine (LMV) therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin (TB) were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C (HBsAg subtype adw) with immune escape mutations, F8L, S34L, F41S, G44V, F93C, V96G, L110I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.     

Frequency of hepatitis B antigen in blood donors

Routine testing of all blood donations for hepatitis B antigen by counter-immunoelectrophoresis was started in April 1971. The frequency of HBAg carriers among apparently healthy volunteer blood donors in the Toronto Centre of the Canadian Red Cross Blood Transfusion Service was 15 in 10,000 with a male:female ratio of 6:1. Excluding penitentiary inmates, the highest incidence was among young, male, non-Anglo-Saxon city dwellers.A system of notification of HBAg-positive donors was developed, through which a carrier is referred to a special clinic for clinical and pathological evaluation.A survey of hospital patients indicated an incidence of HB antigen 3.5 times that of our healthy donor population. A comparison of the number of post-transfusion hepatitis cases occurring before and after the commencement of routine testing for HBAg showed a marked reduction in reported cases in 1971.     

Liver enzyme concentrations as measure of possible infectivity in chronic asymptomatic carriers of hepatitis B.

Fifty-two British-born blood donors who were chronic carriers of hepatitis B surface antigen (HBsAg) were tested for the presence of hepatitis B e antigen (HBeAg) and antibody to HBeAg by an immunoradiometric assay. The presence of HBeAg was closely associated with a slight rise in serum liver enzyme concentrations, a high HBsAg titre, and male sex. We suggest that the finding of persistently raised serum liver enzyme concentrations in an asymptomatic HBsAg carrier might be useful as a likely indicator of HBeAg and high infectivity.     

Consideration of Viral Resistance for Optimization of Direct Antiviral Therapy of Hepatitis C Virus Genotype 1-Infected Patients

Different highly effective interferon-free treatment options for chronic hepatitis C virus (HCV) infection are currently available. Pre-existence of resistance associated variants (RAVs) to direct antiviral agents (DAAs) reduces sustained virologic response (SVR) rates by 3–53% in hepatitis C virus (HCV) genotype 1 infected patients depending on different predictors and the DAA regimen used. Frequencies of single and combined resistance to NS3, NS5A and NS5B inhibitors and consequences for the applicability of different treatment regimens are unknown. Parallel population based sequencing of HCV NS3, NS5A and NS5B genes in 312 treatment-naïve Caucasian HCV genotype 1 infected patients showed the presence of major resistant variants in 20.5% (NS3), 11.9% (NS5A), and 22.1% (NS5B) with important differences for HCV subtypes. In NS3, Q80K was observed in 34.7% and 2.1% of subtype 1a and 1b patients, respectively while other RAVs to second generation protease inhibitors were detected rarely (1.4%). Within NS5A RAVs were observed in 7.1% of subtype 1a and 17.6% in subtype 1b infected patients. RAVs to non-nucleoside NS5B inhibitors were observed in 3.5% and 44.4% of subtype 1a and 1b patients, respectively. Considering all three DAA targets all subtype 1a and 98.6% of subtype 1b infected patients were wildtype for at least one interferon free DAA regimen currently available. In conclusion, baseline resistance testing allows the selection of at least one RAVs-free treatment option for nearly all patients enabling a potentially cost- and efficacy-optimized treatment of chronic hepatitis C.     

An association between α1-antitrypsin phenotype and chronic liver disease

Summary The phenotypes of alpha-1-antitrypsin have been analyzed by isoelectric focusing on polyacrylamide gels in 232 healthy Japanese blood donors and in 240 Japanese patients with chronic liver diseases: 69 with chronic active hepatitis, 122 with liver cirrhosis, 41 with hepatocellular carcinoma and 8 with primary biliary cirrhosis. The liver cirrhosis patients had a gene frequency of 0.07 forPI ^* M3, which was significantly higher (P<0.01) than that (0.03) in blood donors. The gene frequency of PI ^* M3 was significantly increased in cryptogenic liver cirrhosis (P<0.05), and there was a tendency toward an increased frequency of PI ^* M3 in post-transfusion groups, and in primary biliary cirrhosis. There were also tendenciestoward increased frequencies of PI ^* M3 in cryptogenic and post-transfusion groups of patients with chronic active hepatitis. The present study indicates that PI ^* M3 is a genetic or predisposing factor for chronic liver diseases, especially for cryptogenic and/or non A-non B viral chronic liver disease and also for primary biliary cirrhosis.     

Integration of HBV-DNA into liver and hepatocellular carcinoma cells during persistent HBV infection

The hepatitis B virus carrier state (persistent HBV infection) is characterized by the presence of viral surface antigen (HBsAg) and virion particles (Dane particles) in the blood. From 1% to 10% of carriers develop chronic liver disease and/or hepatocellular carcinoma. Recent studies have demonstrated integrated HBV-DNA in hepatocellular carcinomas and in several human hepatoma cell lines. In hepatoma patients, integrated HBV-DNA has been found in all HBsAg carriers. Nontumorous liver also revealed integrated HBV-DNA with the same or a different hybridization pattern from that observed in the tumor. To explore when integration occurs, carriers of short-term (less than 2 years) or long-term (greater than 8-10 years) were evaluated. DNA extracts from percutaneous (needle) liver biopsies showed free viral DNA with no specific integration bands in short-term carriers. In long-term carriers, HBV-DNA was integrated into the host genome with either a diffuse or a unique hybridization pattern. HBV-DNA integration correlated with the duration of the carrier state and absence of virions in the serum but did not correlate with histologic evidence of chronic hepatitis. These studies suggest that integration of HBV-DNA occurs during persistent HBV infection irrespective of liver disease and precedes development of hepatocellular carcinoma.     

<Emphasis Type="Italic">Herpesvirus ateles</Emphasis>, a New Lymphoma Virus of Monkeys

THERE has been a marked increase of post-transfusion hepatitis associated with the increased utilization of blood and its products. The discovery of a reaction of serum from multiple transfused haemophiliacs with serum from patients suffering from hepatitis^1,2 has made it possible to analyse the hepatitis associated antigen (HAA), the agent associated with the transmittance of hepatitis. HAA is currently detected using haemophiliac serum as the antibody source and standard serological techniques, that is, immunodiffusion, complement fixation and immunoelectro-osmophoresis³. This report describes a latex agglutination procedure which is compatible with the existing technology in blood banks as well as being very rapid and sensitive. The assay is based on the agglutination of antibody-absorbed latex particles by HAA contained in the test serum.     

Genetic Diversity and Tissue Compartmentalization of the Hepatitis C Virus Genome in Blood Mononuclear Cells, Liver, and Serum from Chronic Hepatitis C Patients

The degree of genetic variability in the hypervariable region 1 of hepatitis C virus (HCV) was analyzed by cloning and sequencing HCV genomes obtained in paired samples of serum, liver tissue, and peripheral blood mononuclear cells (PBMC) from four chronic hepatitis C patients. Genetic variability in serum was higher than in liver tissue or PBMC at the level of complexity (the number of different sequences obtained from each type of tissue) as well as at the level of genetic distance between all pairs of sequences within each tissue (compared by the Student t test; P < 0.001 for two patients and P < 0.01 for another). The spectrum of viral genomes differed among the three types of tissue, as shown by segregation of sequences according to their tissue of origin in phylogenetic analysis and by statistical analysis of mean genetic distances observed between sequences obtained from different tissues (P < 0.001), but sequences from liver tissue and PBMC were more closely related to each other than to those from serum.     

Prospective study of post-transfusion hepatitis after cardiac surgery in a British centre.

A series of 248 consecutive patients undergoing cardiac surgery were examined in a prospective study of post-transfusion hepatitis in a single British centre. Patients received a total of 1796 units of blood or blood products (mean blood transfusion 6.28 units per patient). During five to 30 days after operation 38 of the patients showed an increase in serum transaminase activities. There was no serological evidence for fresh infection by hepatitis A or B virus, cytomegalovirus, Epstein-Barr virus, or herpes virus in any of these patients. The increase in transaminase activities was unexplained and reached over 100 IU/l (normal less than 40 IU/l) in six patients. The incidence of acute short incubation post-transfusion non-A, non-B hepatitis was therefore thought to be 2.4%. These six patients had normal liver function six months after transfusion but a further two of the surviving 228 patients had raised serum transaminase activities at six months. In one of these, liver biopsy disclosed chronic persistent hepatitis; in the other, alcoholic liver disease was suspected. The incidence of significant chronic liver disease after blood transfusion possibly attributable to a non-A, non-B hepatitis agent was therefore only 0.4%.