Post-transfusion hepatitis. Sudden drop of its incidence associated with hyperbilirubinemic donors disqualification

The lacking impact of various precautions on the incidence of post-transfusion hepatitis (PTH) in the last 15 years is presented. In 1984, however, PTH dropped from 0.12 to 0.04%. This PTH drop did not coincide with the disqualification of HBsAg carriers, nor with that of high ALT, nor with the introduction of complete voluntary donorship in 1982, but with the systematic exclusion of hyperbilirubinemic donors. Circulating immune complexes (CIC) were found in 28.9% of PTH compromised donors, and CIC are therefore supposed to be a marker of PTH risk even if HBsAg was not demonstrable. Re-examining donors compromised in 120 PTH found 12.4% HBsAg carriers who had not been detected by CIEP prior to the transfusions. Accumulation of more than one HBsAg positive transfusion in 56.5% of the PTH patients suggests a cumulative effect. The inability of specific tests to identify sources of infection in 50% of PTH suggests that doubts must be raised as to their post-transfusional origin. This thesis is also supported by the relative increase of this group after the considerable drop of PTH. The importance of viral sources non-B and B undetectable by sensitive specific methods must be emphasized. The latter is in accordance with the observed PTH drop due to a non-specific marker effect. The bilirubin level screening in each donor before stored blood collection is recommended by means of the described extended AST screening test and, besides HBsAg screening, this is supposed to be the most effective precaution for preventing PTH.     

High-titered anti-HBs plasma donors--another form of post-hepatitic immunopathy syndrome

In the population of 55 high-titered anti-HBs donors only 23 tolerated plasmapheretic collections without intermittent elevations or ALT activity. In 4 persons a RIA-detected HBsAg circulated along with high-titered anti-HBs. In 73.8% of donors anti-HBs was accompanied by an anti-HBe antibody which also appeared in the HBIG preparation HEPAGA and can perhaps participate on its protective influence. Circulating immune complexes (CIC) were detected in 89.1%. No HBsAg, HBeAg, or albumin were detected in CIC isolated from anti-HBs sera in spite of their content in CIC isolated from HBsAg carriers. Thus, CIC carriers found in normal population with a prevalence of 1.0% can be divided into 0.6% of HHsAg-containing CIC and 0.4% of HBsAg-lacking CIC carriers with anti-HBs attesting the hepatitic origin in a considerable part of them. The continuing production of alienated CIC-forming antigens and a common origin combine these two forms of post-hepatitic development to a syndrome of post-hepatitic immunopathy which seems to be the most frequent source of CIC in a normal population. All the donors and HEPAGA were anti-HBc positive, as well, but this antibody possessed the IgM character only in 4.3% of the donors. Mean serum ferritin levels in the anti-HBs donors were distinctly higher than those found in normal populations of both men and women but the differences were statistically not significant due to high variability.     

Prevalence and significance of hepatitis B surface antigen in a general hospital.

Over a 6-month period 2025 patients admitted to New Mount Sinai Hospital, Toronto were screened for hepatitis B surface antigen (HBsAg) by counter-immunoelectrophoresis (CIEP) and radioimmunoassay (RIA). CIEP detected 12 HBsAg-positive patients and RIA 16. RIA is therefore the more sensitive test for HBsAg. Of the 16 patients 2 had liver disease previously diagnosed, 3 had malignant disease and 11 were asymptomatic carriers. Of the 11 carriers all were born in countries where the carrier rate is known to be high. Routine screening of hospital patients on admission is of no value in detecting unsuspected liver disease but is of value in detecting asymptomatic carriers, which is of importance for the patient and his family. Routine screening tests for HBsAg in Canadian hospitals that treat many patients born in countries with a known high HBsAg prevalence is recommended. Routine screening is also recommended in all hospitals in Mediterranean and Asian countries.     

Hepatitis B antigen in screened blood units for transfusion in renal dialysis patients

Blood units for transfusion are screened routinely in Ontario for the presence of hepatitis B antigen (HB-Ag) by counter-immunoelectrophoresis (CIEP). Since the radioimmunoassay (RIA) method is more sensitive for this purpose we used it to test blood units delivered to the hospital''s Renal Dialysis Unit in order to determine if HB-Ag-carrying blood donors were being missed by the less sensitive CIEP method.Out of the 606 blood units tested, eight were found to contain HB-Ag, an incidence of 13 out of 1000 donors. This finding indicates that the counter-immunoelectrophoresis method is insufficiently sensitive as a safe screening method for detection of hepatitis antigen.     

Screening of Danish blood donors for hepatitis B surface antigen using a third generation technique.

The profit to be gained by testing Danish blood donors for hepatitis B surface antigen (HBsAg) with a third generation technique instead of the currently used immunoelectrophoresis was investigated by additional screening of 48 750 blood units by radioimmunoassay three weeks after donation. Twenty nine units were positive for HBsAg on radioimmunoassay (0.059%). Only six of these were found by immunoelectrophoresis (0.012%). Most of the 23 donors positive on radioimmunoassay and negative on immunoelectrophoresis were healthy carriers of HBsAg (20) or had asymptomatic chronic liver disease (two). One donor had acute hepatitis B. Fifteen of the 23 blood units were transfused. The 15 recipients were monitored biochemically and serologically for up to nine months. One recipient developed fulminant hepatitis B, three developed acute hepatitis B, and one became a healthy carrier of HBsAg. All these patients had received blood from healthy carriers of HBsAg. Two recipients were immunised against HBsAg, and in one patient no seroconversion was observed. The remaining recipients died soon after transfusion or were protected by antibodies to HBsAg that had been present before the transfusion. Testing of Danish blood donors using a third generation technique identified a substantial number of donors positive for HBsAg overlooked by immunoelectrophoresis. Most of these donors were healthy carriers of HBsAg. Blood taken from such carriers is highly infectious when transfused, probably because of the large amount of material transmitted.     

Prevalence of HBsAg and HBsAg sub-types in the Canadian blood-donor population

After 8 years of screening all blood donations in Canada for HBsAg, first by CIEP and later by RIA, the prevalence of HBsAg in the regular panel of "repeat" donors has been reduced from 267/10(5) to 39/10(5). Marked geographic variations exist, but the available data do not indicate whether the high prevalence of HBsAg in young adults, particularly males, may be a factor. The ad : ay subtype ratio across Canada is 2.0, but noticeable geographic differences are present, varying from 3.5 in Quebec to 0.5 in the Atlantic Provinces.     

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.     

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.     

Immunoenzyme analysis of antigen-specific determination of HBsAG-containing circulating immune complexes (CIC HBsAG/IgM and CIC HBsAG/IgG) in blood serum of patients with HBV-infection]

A complex enzyme immunoassay (ELISA) has been designed for antigen-specific determination of HBsAg-containing circulating immune complexes (CIC HBsAg/IgM and CIC HBsAg/IgG) in human blood sera in parallel with registration of free HBsAg and specific antibodies to viruses of hepatitis A, B and D. It is shown that effective formation of HBsAg-containing CIC serologically is registered predominantly as a mutually incompatible marker with detection of free HBsAg (in 70-85% of the cases). CIC HBsAg/IgM and CIC HBsAg/IgG may be registered both in parallel and as mutually exclusive markers. Effective formation of HBsAg-containing CIC in the presence of anti-HBsAg occurs in case of a mild course of viral hepatitis of epidemic and sporadic type, while in severe forms of VH-free HBsAg is predominantly detected thus pointing either to ineffective formation of HBsAg-containing CIC or to their continuous registration with demonstration of the effect of delay of witching of anti-HBsM over to anti-HBsG (or CIC HBsAg/IgM to CIC HBsAg/IgG). It was also found that in case of epidemic VH in Tajik SSR (1987) serologically marked as VH both A and B convalescent phase was characterized by parallel disappearance (or lowering of the titer levels) of HBsAg-containing CIC and class M antibodies to both hepatitis A (anti-HAV M) and B (anti-HBcM, anti-HBsM) along with the containing parallel registration of relevant G-antibodies (anti-HAV G/anti-HBcG). This observation requires further studies both in terms of close association of viruses of hepatitides A and B and with regards to possible antigenic mimicry.     

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.     

Characteristics of the formation of the HBsAg carrier state among pregnant women and newborn infants and their role in the spread of hepatitis B

The authors analyze the incidence rate of HBsAg carriership among 8, 120 pregnant women and 261 newborn infants at different periods after birth. The levels of HBsAg carriership among pregnant women and the members of their families, as well as among the personnel of maternity clinics and blood donors, have been established. The rate and time of the detection of HBsAg in infants born to mothers found to be HBsAg carriers have been determined. Measures for the prophylaxis of hepatitis B are discussed with due regard to the specific epidemiological features of the spread of HBsAg carriership, established in this study, and to the presence of antibodies to HBsAg among the above-mentioned groups of the population.     

Transmission of HBsAg from mother to infant in four ethnic groups.

Antenatal screening in the West Midlands during a three-year period identified 297 mothers who were chronic carriers of hepatitis B surface antigen (HBsAg)--a prevalence of about 1 in 850. About half of their infants had HBsAg in the cord blood, but of 122 infants followed up for over three months (mean 8.5 months) only 17 (14%) were still positive for HBsAg. Cord-blood HBsAg-positivity was evenly distributed among different ethnic groups, but the transmission rate was highest among the Chinese, and no carriers were discovered among 39 European infants. Raised serum transaminase concentrations were found in some of the carrier infants who were otherwise healthy. The results suggest that adequate follow-up of HBsAg-positive infants may be achieved by tests at 4 months and 1 year of age, and that the role of breast-feeding in mother-to-infant transmission of HBsAg is unimportant. The Chinese community may be a suitable population in which to test the effectiveness of specific immunoglobulin administration at birth in preventing the development of the HBsAg carrier state.     

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.     

New strategies for blood donor screening for hepatitis B virus: nucleic acid testing versus immunoassay methods

Serologic testing for hepatitis B virus (HBV) surface antigen (HBsAg) and antibody to HBV core antigen (anti-HBc) has historically been the foundation of blood screening, while HBV nucleic acid testing (NAT) was recently developed to detect HBsAg-negative, anti-HBc-negative blood units donated during early acute infection. Comparison data on seroconversion panels using HBsAg assays of varying sensitivities and pooled- or single-sample NAT, along with viral load estimates corresponding to HBsAg assay detection limits, have provided information on the theoretical benefits of NAT relative to HBsAg. Model-derived estimates have generally been predictive of the yields of DNA-positive, HBsAg-negative window period blood units detected in a number of studies from Europe, Japan, and the US. Studies indicate that the added benefit of pooled-sample NAT is relatively small in areas of low endemicity, with greater yields in areas highly endemic for HBV. Single-sample NAT would offer more significant early window period closure and could prevent a moderate number of residual HBV transmissions not detected by HBsAg assays; however, no fully automated single-sample HBV NAT systems are currently available.Even single-sample HBV NAT may not substitute for anti-HBc screening, as indicated by studies of donors with isolated anti-HBc who have extremely low DNA levels undetectable by standard single-sample NAT and who have been associated with transfusion-transmitted HBV. Moreover, HBsAg testing may still be needed even in the setting of combined anti-HBc and NAT screening. HBsAg-positive units from donors in the chronic stage of infection may contain very low or intermittently detectable DNA levels that single-sample NAT would miss. Although such donors are usually anti-HBc reactive and would be interdicted by anti-HBc screening, some lack anti-HBc. Extensive parallel testing will be needed to determine whether single-sample NAT in combination with anti-HBc might be sufficient to detect all the infectious donors currently interdicted by HBsAg testing. In countries that do not screen for anti-HBc, HBsAg testing would be the only means of detecting donations from chronically infected individuals with low/intermittently detectable DNA, since even single-donor NAT would not identify these potentially infectious blood units. In the future, the current fully automated HBsAg assays may incorporate significant sensitivity improvements, and automated single-sample HBV NAT may become a reality. Each country will need to develop its blood screening strategy based on HBV endemicity, yields of infectious units detected by different serologic/NAT screening methods, and cost effectiveness of test methods in ensuring blood safety.     

Prevalence of hepatitis B viral markers in Vietnamese blood donors

Serum samples were assayed using radioimmunoassay in 573 Vietnamese blood donors living in Hano? (North Viet Nam). 66 (11.5%) subjects were HBsAg-positive. Of these 66 HBsAg carriers, 17 (25,8%) were positive for hepatitis B e antigen (HBeAg) and 43 (65.1%) for antibody to HBeAg (anti-HBe). 22 (3.8%) subjects were positive for antibody to hepatitis B core antigen (anti-HBc) alone. 402 (70.2%) subjects were positive for antibody to HBsAg (anti-HBs). This anti-HBs percentage increased with age. Only 83 (14.5%) subjects were negative for all hepatitis B viral (HBV) markers. This no HBV markers percentage decreased with age. The chi 2 test showed a non significant difference for frequencies of HBsAg, anti-HBc alone, anti-HBs but a significant one for frequencies of no HBV markers in men and women.     

Characteristics of the distribution of the markers of hepatitis B vir us infection among the healthy population of the Tadzhik SSR and Azerbaijan SSR

A total of 708 healthy persons in Tajikistan and 576 healthy persons in Azerbaijan, these groups comprising persons of both sexes and different age groups, were examined by the method of double gel immunodiffusion (the gel precipitation test) and by the passive hemagglutination test for the presence of the markers of hepatitis B virus (HBV) infection (HBsAg and HBeAg) and antibodies to them. This investigation showed that, in accordance with the level of hepatitis B morbidity, HBsAg was significantly more often detected among the population in Tajikistan (7.2%) than in Azerbaijan (2.8%). In both republics HBV carriers occurred most frequently among children aged 1-4 years (4.0% in Azerbaijan and 13.9% in Tajikistan), and among men more frequently than among women. In accordance with different intensity of the spread of HBV infection in the territories under comparison, differences in the age structure of the immune population were noted: in Tajikistan the formation of the immune layer occurred most frequently among younger age groups and in Azerbaijan, among senior adult age groups. The presence of a considerable percentage of persons with HBe-antigenemia (14.3-14.9% as determined by the gel precipitation test) among HBV carriers, observed in Tajikistan and in Azerbaijan, indicates that some of them have undetected chronic hepatitis B.     

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.     

FINDRISK questionnaire combined with HbA1c testing as a potential screening strategy for undiagnosed diabetes in a healthy population

Despite the efforts to control the epidemic of diabetes the total number of people living with diabetes is still steadily rising. In order to detect people at risk, cost-effective, convenient, and sensitive screening tools to assess the diabetes risk and to detect undiagnosed type 2 diabetes need to be developed and implemented in the primary care setting. To evaluate the combination of the well established FINDRISK questionnaire and HbA1c testing as a potential screening strategy the data obtained from 671 blood donors were analyzed for a potential correlation with the results of an oral glucose tolerance test. Based on the oral glucose tolerance test, 65 blood donors (9.7%) were newly diagnosed with diabetes, 336 (50.1%) with prediabetes, and 270 (40.2%) had a normal test result. Of the 401 blood donors diagnosed with prediabetes or diabetes 322 (80.3%) had a HbA1c between 5.7% and 6.4% and 27 (6.7%) with a HbA1c of 6.5% or greater. The majority of the blood donors newly diagnosed with diabetes or prediabetes (n=327) had a FINDRISK result of 12 points or higher. ROC analyses confirmed that the optimal cut off levels were for FINDRISK ≥ 12 points and for HbA1c ≥ 5.9%. Thus, a 3-step screening strategy applying the FINDRISK questionnaire followed by HbA1c testing and performing an oral glucose tolerance test on selected individuals could be a cost-saving approach for screening large populations and identifying people at risk for diabetes or undiagnosed diabetes.     

Hepatitis B antigen in Montréal blood donors: childhood institutionalization as an epidemiologic factor.

In 1971 the Canadian Red Cross blood tranfusion service instituted routine screening for HBAg of all blood donors, using nationwide a standardized counterimmunoelectrophoretic technique. The prevalence of carriers in the Province of Québec is unusually high (0.51%), being 3 to 12 times higher than in the other nine provinces. Among the carriers found in the Montréal area 289 volunteered to be seen by our group for an extensive interview and a series of laboratory tests. There were 243 men and 46 women; their ages ranged from 18 to 55, 90% being less than 40. Twenty-nine were of foreign origin and 260 were born in Canada. The epidemiologic data revealed that the reservoir of HBAg carriers among the blood donors of the Montréal area was found predominantly in the autochthonous population of French origin. Moreover, it appeared that 149 (52%) had lived in institution when they were infants or children: 127 were orphans and had been placed in institutions as newborns or babies, and 22 others had lived in institutions for at least 1 year between the ages of 5 and 10. This was by far the most important single epidemiologic factor that could contribute to the explanation of the abnormally high prevalence of HBAg carriers in the population studied.     

Success of a program of routine prenatal screening for hepatitis B surface antigen: the first 2 years.

Prenatal screening for hepatitis B surface antigen (HBsAg) restricted to women with defined risk factors for chronic hepatitis B virus (HBV) infection fails to identify many carriers. A centralized program of routine HBsAg screening for all pregnant women in Alberta was introduced in 1985. We collected and analysed data for the first 2 years of the program in Edmonton to determine the frequency of risk factors for HBsAg positivity, the proportion of multiparous HBsAg-positive women not identified in previous pregnancies, the efficiency and cost-effectiveness of providing immunoprophylaxis to infants at risk of HBV infection and the degree of success in inducing adequate protection. A total of 149 women (158 pregnancies) were found to be HBsAg positive. Risk factors were readily ascertainable for 85% of the women; the remaining 15% would not have been identified through risk-selective screening. The most common risk factors were Oriental ethnic origin, history of hepatitis, jaundice or multiple transfusions of blood or blood products, and occupational exposure to blood. Although 86% of the multiparous HBsAg-positive women had risk factors, only 7% had been identified in previous pregnancies. The Alberta program appears to be cost-effective. We conclude that only routine prenatal screening will identify all infants at risk of perinatal HBV infection and that a comprehensive public health program involving central laboratories, private physicians and public health staff can be highly effective and efficient in protecting infants against hepatitis B.