Cases Of Post-transfusion Hepatitis Research Articles

Parenterally Transmitted Non-A, Non-B Hepatitis

In 1972 a nonsocomial outbreak of parenterally transmitted hepatitis affected both marrow transplant patients and normal platelet donors in an oncology unit. Because of the characteristics of the clinical illness, the incubation period of 27 days, and the effect of immune serum globulin on the clinical illness, the outbreak was attributed to hepatitis A; there was no serologic evidence of either hepatitis B virus or cytomegalovirus infection. Stored serums from this outbreak were re-examined by more recently developed serologic techniques for evidence of hepatitis A (HA) virus infection. Ten patients and donors had undetectable anti-HA titers before illness and none seroconverted; five persons had pre-existent anti-HA titers and showed no further rise in convalescent serums. The serum of one patient was inevaluable. With the availability of serologic techniques for the diagnosis of both hepatitis A and hepatitis B virus infections, it is clear that most cases of post-transfusion hepatitis are not due to either of these agents, and short-incubation-period hepatitis can not be assumed to be hepatitis A without further investigation.

NON-A, NON-B POST-TRANSFUSION HEPATITIS

To clarify the role of hepatitis-A virus (H.A.V.) in the aetiology of post-transfusion hepatitis unrelated to hepatitis-B virus, we have tested and titred pre-transfusion and convalescent serum samples from 32 patients for antibody to hepatitis-A antigen (anti-HA) by quantitative immune adherence hæmagglutination. 12 patients had no detectable anti-HA in either pre-transfusion or late convalescent serum; the other 20 had anti-HA in pretransfusion serum and no significant change in titre during convalescence. This study excludes. H.A.V. as the agent responsible for these cases of post-transfusion hepatitis and supports the existence of "non-A, non-B" hepatitis virus(es).

Absence of Complete Homologous Immunity in Hepatitis B Infection After Massive Exposure

Evidence from prospective studies of human cases of posttransfusion hepatitis observed among 299 cardiac surgery patients, and from each of three experimentally challenged chimpanzees, indicates that immunity to hepatitis B infection can be overcome by massive challenge doses. However, all cases of hepatitis in patients with prior immunity have been subclinical. Chimpanzees developed hepatitis and HBs antigenemia when challenged with hepatitis B virus that had an antigenic subtype identical to that used in the primary infection. This response provides evidence against the role of differences in antigenic composition of initial and challenge strains of virus as an explanation for incomplete homologous immunity.

Blood Donors—Paid or Volunteer?

To the Editor.— Dr Allen, with characteristic zeal in the crusade for voluntary blood donation, has missed the point of our article (234:1051,1975) in his letter (235:1327, 1976). The objective of our article was to report our experience in changing from a paid to a volunteer blood donor program in compliance with the American Association of Blood Banks definition of a volunteer donor. Our results emphasize the problem with the definition of volunteer vs paid blood donor. Dr Allen apparently believes he can intuitively define paid and volunteer donor. If the definition were as clear as he implies, there would not have been such a variety of opinion on this subject expressed at the March 18, 1976, Food and Drug Administration public meeting on blood labeling. We have received inquiries concerning the actual number of cases of posttransfusion hepatitis identified as a result of blood transfusion from our volunteer and

Studies of the “e” Antigen in Acute and Chronic Hepatitis

Sera from well individuals, including controls and asymptomatic HBsAg carriers, post-transfusion hepatitis cases, and chronic active liver disease patients were examined for the presence of "e" antigen and e antibody by rheophoresis. Our data confirm the specific association between the e determinant and hepatitis B infections and indicate that e antigen is closely associated with evidence of chronic hepatic dysfunction, in contrast to the association of e antibody with hepatic normalcy in HBsAg carriers. However, these correlations are not absolute and, therefore, it should not be inferred that all e antigen-positive individuals will develop chronic hepatitis nor, conversely, that presence of e antibody invariably protects against the development of chronic hepatitis.

Etiological Spectrum of Post-Transfusion Hepatitis

Frequent occurrence of post-transfusion hepatitis continues despite screening for Australia antigen in blood before transfusion and elimination of commercial donor sources. The majority of these cases appears unrelated to hepatitis B virus. Preoperative, acute, and convalescent serra were screened for evidence of hepatitis B, hepatitis A, Epstein-Barr, and cytomegalovirus exposure in 34 cardiac surgery patients developing post-transfusion hepatitis postoperatively. Four patients showed evidence of hepatitis B infection and 3 patients developed significant antibody titer rises to cytomegalovirus. No patient showed evidence for acute hepatitis A infection postoperatively in response to blood transfusions. Epstein-Barr virus was also not responsible for any cases of post-transfusion hepatitis. Presently available laboratory methods failed to implicate hepatitis A, Epstein-Barr, or cytomegalo-virus in the majority of non-B post-transfusion hepatitis cases. This suggests that identification and characterization of additional hepatitis-producing agents will be required to define further the epidemiology of post-transfusion hepatitis and develop measures for its prevention.

Detection of hepatitis B surface antigen among Scottish blood donors: evaluation of sensitive tanned-cell haemagglutination-inhibition test.

A total of 70 224 blood donations were tested at three Scottish blood transfusion centres for hepatitis B surface antigen /HBsAg) by an economical haemagglutination-inhibition method (E.H.A.I.) and the results compared with those of counterelectrophoresis (C.E.P.). A further 4086 donations were tested using the Wellcome turkey cell haemagglutination test, C.E.P., and E.H.A.I.E.H.A.I. was also compared with commercial haemagglutination and radioimmunoassay reagents for sensitivity and specificity against several established antigen panels and used to reinvestigate counterelectrophoresis-negative blood donations implicated in post-transfusion hepatitis. E.H.A.I. combines the inherent specificity of an inhibition reaction with a sensitivity equal to that of commercial radioimmunoassay and haemagglutination kits but at a fraction of the cost. The assessment of 70 224 blood donations in three regions showed that E.H.A.I. detected more antigen-positive blood donations than C.E.P. Results of retesting more than 100 blood donors implicated in 10 cases of post-transfusion hepatitis suggested that the use of E.H.A.I. or a test of similar sensitivity in place of C.E.P. may significantly reduce the incidence of this complication.

A New Antigen-Antibody System

A new antigen-antibody system was recently described in hepatitis B surface antigen (HB_sAg)-positive sera. Despite indications of heterogeneity in specificity, the designations "<i>e</i>antigen" and "<i>e</i>antibodies" are used for the system as such in this article. Eight of 17 long-term carriers of HB_sAg with a histological picture of chronic persistent hepatitis or chronic aggressive hepatitis carried the<i>e</i>antigen, while none had demonstrable<i>e</i>antibodies in serum. Ten of 12 healthy carriers with e antibodies were blood donors who had donated 95 units of blood; none of these carriers was associated with a reported case of posttransfusion hepatitis. In five individuals in the incubation stage of hepatitis B,<i>e</i>antigen appeared simultaneously with HB_sAg but before the rise in transaminase levels. This finding further links<i>e</i>antigen to hepatitis B. (<i>JAMA</i>231:356-359, 1975)

A new antigen-antibody system. Clinical significance in long-term carriers of hepatitis B surface antigen.

A new antigen-antibody system was recently described in hepatitis B surface antigen (HBSAG(-positive sera. Despite indications of heterogeneity in specificity, the designations "e antigen" and "e antibodies" are used for the system as such in this articly. E'IGHT OF 17 long-term carriers of HBSAg with a histological picture of chronic persistent hepatitis or chronic aggressive hepatitis carried the e antigen, while none had demonstrable e antibodies in serum. Ten of 12 healthy carriers with e antibodies were blood donors who had donated 95 units of blood; none of these carriers was associeated with a reported case of posttransfusion hepatitis. In five individuals in the incubation stage of hepatitis B, e antigen appeared simultaneously with HBSAg but before the rise in transaminase levels. This finding further links e antigen to hepatitis B.

LONG-INCUBATION POST-TRANSFUSION HEPATITIS WITHOUT SEROLOGICAL EVIDENCE OF EXPOSURE TO HEPATITIS-B VIRUS

An agent other than hepatitis-B (HB) virus seemed to be the cause of 36 (71%) of 51 cases of post-transfusion hepatitis identified during prospective biweekly serological follow-up of 204 cardiovascular-surgery patients. The sera of the 36 cases showed no evidence of the antigen or antibody response expected to accompany infection by HB virus and to be detectable by the sensitive assays used. Incubation periods and clinical and epidemiological features were inconsistent with hepatitis A. Cytomegalovirus-associated seroconversion was no more common among the HB-negative cases than among HB-positive cases or among patients who did not develop hepatitis. The data suggest that a large proportion of long-incubation post-transfusion hepatitis is unrelated to hepatitis B and that control of post-transfusion hepatitis will require identification of a hepatitis virus(es) type C.

Recipient's Hepatitis, an Inevitable Side‐Effect of Blood Transfusion

Abstract. The transfusion of blood with indetectable or only by electron microscope detectable amounts of HAA is presently as inevitable as the transfusion of blood containing no HAA at all, but nevertheless infective for hepatitis A or B. An unknown percentage of so‐called posttransfusion hepatitis cases is surely due to extrahaematogenic infections. In all these cases the manifestation of the disease seems to be due rather to a temporarily enhanced susceptibility of the patients than to the relatively small virus dose. The reported observations give support to the hypothesis that surgery or certain circumstances in close connection with surgery aside from the administration of blood may markedly enhance the susceptibility to hepatitis B manifestation.

Frequency of Australia antigen detected by radioimmunoassay in hepatitis in children.

Ninety-eight serum specimens obtained from 53 cases of hepatitis in children and 11 specimens from 10 cases of biliary atresia were tested for Australia (Au) antigen by radioimmunoassay (RIA). Au antigen was detected in 3 out of 10 cases of post-transfusion hepatitis (30%), in 14 out of 18 cases of viral hepatitis (78%) without known parenteral exposure to blood or blood products and in 2 out of 2 cases of chornic hepatitis (100%). In contrast to them, antigen was detected in none of 23 cases of neonatal hepatitis and 10 cases of biliary atresia.

Immune response in patients who received blood containing serum hepatitis antigen. Studies with the passive hemagglutination technique.

Conventional methods for detection of SH (Australia antigen, HAA) antigen and corresponding antibody, such as agar gel diffusion (AGD), immunoelectroosmophoresis (IEOP), and complement fixation (CF), have failed to incriminate hepatitis virus type B in a major portion of cases of posttransfusion hepatitis. 1,2 It has not been possible to determine whether this reflects only the inadequate sensitivity of these assay methods or whether these findings reflect the role of other viruses, lacking an association of the SH antigen, in the etiology of posttransfusion hepatitis. It has been recognized that introduction of more sensitive methods, such as radioimmune assay 3 or hemagglutination inhibition (HAI) 4 may provide an answer. We report an investigation of patterns of immune response as shown by passive HA technique in 35 patients inadvertently transfused with blood containing SH antigen. Serological evidence of infection with hepatitis virus type B has been obtained in 34 of the 35

Post-transfusion hepatitis: A review and prospectus

Sixty-one cases of post-transfusion hepatitis reported to a community blood bank are reviewed. Patients exhibited a wide spectrum of clinical disease. A high risk was observed with transfusion of components prepared from pooled donor plasma. Australia antigen was present in 58 per cent of the patients with hepatitis and was three times more frequent in implicated donors than in the general donor population. Careful donor selection, routine screening for Australia antigen, and judicious use of blood and components should reduce the incidence of post-transfusion hepatitis.

Human Serum Bilirubin

Abstract The technic of Powell (3) for the estimation of serum bilirubin has been modified by reading the optical density of the solutions shortly after mixing the reagents and using a standard based on a more appropriate solution of crystalline bilirubin in pigment-free serum. Seven specimens of bilirubin were examined spectrophotometric-ally; the disproportionality of the millimolar extinction coefficients at 453 mµ for the free-bilirubin and at 532 mµ for, the azobilirubin complex indicated the presence of an unreactive yellow pigment. The destructive effect of sunlight on solutions of biirubin, noted in the literature, was confirmed, hence all estimations were done without delay or exposure to light for any length of time. The results obtained on apparently healthy blood donors, to detect possible carriers of homologous serum hepatitis, revealed no definite correlation between previous history of jaundice and increased serum bilirubin values, but as a precautionary measure individuals with values above 1.5 mg. per 100 ml. were not accepted as donors. When 200 random values were plotted, the distribution curves gave a mean value higher for males than females. Furthermore, 108 donors (among the 25,000 screened) had biirubin values greater than 1.5 mg. per 100 ml. The eleven females of the group did not maintain high values, while 30 males recorded high values on more than one occasion, some consistently. No significant correlation was found between high bilirubin values and a previous history of jaundice, nor were any cases of posttrans-fusion hepatitis traced to these donors. Somewhat arbitrarily, 1.5 mg. per 100 ml. was chosen as the upper limit of normal.