James W. Mosley

Hepatitis C virus infection in post-transfusion hepatitis : an analysis with first- and second-generation assays

Abstract Background. The causes of post-transfusion non-A, non-B hepatitis are still not fully defined, nor is it clear how accurate the tests are that are used to screen blood donors for hepatitis C virus (HCV) and to diagnose post-transfusion hepatitis caused by infected blood. Methods. We used two first-generation enzyme-linked immunoassays (ElAs) and one second-generation immunoassay to test for anti-HCV antibodies in serum samples collected between 1976 and 1979 in the Transfusion-Transmitted Viruses Study (from 1247 patients who underwent transfusion and 1235 matched control subjects who did not receive transfusions). We tested serum collected before and after infection from the patients in whom non-A, non-B hepatitis developed, serum from their blood donors, and serum from 41 of the control subjects who had hepatitis unrelated to transfusion. Results. Of the 115 patients in whom post-transfusion non-A, non-B hepatitis developed, the initial serum samples of 111 were anti-HCV-negative; after hepatit...

Serum alanine aminotransferase of donors in relation to the risk of non-A, non-B hepatitis in recipients. The Transfusion-Transmitted Viruses Study.

To evaluate the incidence of post-transfusion hepatitis and factors influencing its occurrence, the Transfusion-Transmitted Viruses Study prospectively followed 1513 transfusion recipients from 1974 through 1979. The attack rate for non-A,non-B hepatitis was 10 per cent. The incidence of hepatitis was directly related to the alanine aminotransferase (ALT) level in blood donors. In recipients of multiple transfusions of blood that had no donor-ALT level above 29 IU per liter the attack rate was 6 per cent or less; at higher donor-ALT levels the attack rate increased progressively, reaching 45 per cent in recipients of units with an ALT of 60 IU or greater. A similar relation was observed among recipients of single units of blood. Moreover, hepatitis developed in 10 of 11 recipients of two units with an ALT level of 45 IU or greater. These data indicate that screening blood for ALT levels would reduce the incidence of non-A,non-B post-transfusion hepatitis.

Hepatitis B Virus Antibody in Blood Donors and the Occurrence of Non-A, Non-B Hepatitis in Transfusion Recipients: An Analysis of the Transfusion-Transmitted Viruses Study

Patients who received transfusions and nontransfused control patients were followed to assess the incidence and cause of post-transfusion hepatitis and to identify donor factors that might relate to risk of hepatitis. We evaluated as risk factors in donors the presence of antibody to hepatitis B virus compared with elevated alanine aminotransferase (ALT) level. Units of blood that were positive for antibody to hepatitis B core antigen (anti-HBc) were associated with a twofold to threefold greater risk of non-A, non-B hepatitis in the recipients than were units without anti-HBc. In the absence of specific serologic tests for non-A, non-B agents, screening of donors for anti-HBc might be considered. Our data suggest that the incidence of non-A, non-B hepatitis might have been reduced by about one third by such screening. However, elevated ALT levels in donors had a similar association with non-A, non-B hepatitis in recipients but would have resulted in fewer units of blood being discarded than would screening for anti-HBc.

Infection with Human Immunodeficiency Virus Type 1 (HIV-1) among Recipients of Antibody-Positive Blood Donations

OBJECTIVE To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipients sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.

Etiology of sporadic hepatitis B surface antigen-negative hepatitis.

We studied serologically 45 adults who had sporadic acute viral hepatitis that was hepatitis B surface antigen (HBsAg) negative. Two cases were due to hepatitis B virus, as demonstrated by the appearance of antibody to hepatitis B core antigen. In three other patients, the serologic pattern was inconclusive. Of 40 non-B cases, 20 were type A hepatitis and 20 were non-A, non-B hepatitis. Clinically, type A and non-A, non-B hepatitis were indistinguishable; one case of fulminant disease occurred in each group. The type A cases were more frequent in young adults; non-A, non-B disease predominated in women 35 years or older. Epidemiologic backgrounds were generally similar, including illicit self-injection; but four transfusion-associated cases were limited to the non-A, non-B group. We conclude that relatively few HBsG-negative cases are due to hepatitis B virus, and that hepatitis A virus and non-A, non-B viruses are both important in acute non-B disease.

Hepatitis B Virus Infection in Dentists

To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strans of that agent in the general population for several decades.

Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients

BACKGROUND: Testing for antibody to hepatitis B core antigen (anti‐HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion‐transmitted hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In a study conducted in the 1970s, 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow‐up visits were available for present‐day assays for HBsAg, HBV DNA, anti‐HBc, and antibody to HBsAg (anti‐HBs). RESULTS: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti‐HBc was detected in six HBsAg‐negative donors. Two other donors were negative in all assays at donation, but positive for anti‐ HBc and anti‐HBs 2 to 4 months later. The remaining donors were negative for all HBV markers, which left five recipient cases unexplained. No HBV transmission was observed when anti‐HBs sample‐to‐ negative control values were > or = 10. CONCLUSION: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg‐negative donors are prevented by anti‐ HBc screening. Anti‐HBc‐positive donors unequivocally positive for anti‐ HBs should be considered noninfectious for HBV and should be allowed to donate. Anti‐HBc screening of paid plasmapheresis donors, supplemented by anti‐HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti‐HBs in plasma pools.

Hepatitis B Immune Globulin as a Prophylactic Measure for Spouses Exposed to Acute Type B Hepatitis

Because the value of usual immune globulin preparations in preventing Type B hepatitis is doubtful, we carried out a double-blind comparison of a control human immune globulin preparation with one--identified as HBIG--that had a high concentration (442 mug per milliliter) of antibodies to surface components of hepatitis B virus. Effectiveness was tested in spouses of patients with acute Type B hepatitis. Within 150 days after injection, nine of 33 spouses in the control group had symptomatic Type B hepatitis, compared with one of 25 spouses receiving HBIG. One non-B case also occurred in the HBIG group. Five control globulin recipients had evidence of subclinical hepatitis B infection, compared with one HBIG recipient. Thus, HBIG appeared effective in suppressing not only disease, but also infection itself. Prophylactic value has been demonstrated in persons who should now be recognized as being at exceptionally high risk.

Occupational risk of hepatitis B infection in hospital workers.

To estimate the risk of hepatitis B virus (HBV) infection among hospital workers, we measured the prevalence of HBV infection in employees in five hospitals in different parts of the country and examined the effect of occupational and non-occupational factors on HBV prevalence. Among 5,697 persons studied, serologic markers of HBV infection were found in 807 (14%). Prevalence of infection was strongly related to race (Asian greater than Black greater than White), sex (male greater than female) and increasing age. Risk related to health occupation, studied by examining the change in HBV prevalence with duration in occupational group, was most strongly correlated with frequency of contact with blood during work. Workers having frequent blood contact had the highest estimated infection rate (1.05 per 100 person-years) and those with moderate contact an intermediate infection rate, compared to a negligible infection rate in workers with no blood contact. Frequency of needle accidents had an independent, positive effect on HBV infection rates, while degree of patient contact had no effect. Infection risk was uniform among all hospitals for groups with frequent blood contact. Among different occupation groups, risk of HBV infection also correlated closely with degree of blood-needle contact during daily work. This study provides a general approach to assessing risk of HBV infection in hospital personnel, and indicates that risk may be most easily estimated by quantitating degree of blood-needle contact during daily work.

Non-A, non-B hepatitis transmission in chimpanzees: a project of the Transfusion-transmitted Viruses Study Group.

Experimental transmission of non-A, non-B hepatitis was apparently accomplished in 5 chimpanzees following inoculation with presumably infectious human sera. Administration of sera from implicated donors with normal alanine aminotransferase (ALT) values, as well as from those with abnormal ALT levels, resulted in the development of ALT abnormalities in the inoculated chimpanzees. Transmission from donors with normal ALT values implies that healthy carriers of non-A, non-B virus exist. Evidence is presented which indicates that a period of viremia precedes the clinical illness by at least 12 days.