Human intravenous immunoglobulins prepared by the cold ethanol fractionation technique of Cohn are considered safe with respect to infectivity. However, there have been several instances of transmission of both hepatitis B and non-A,non-B hepatitis viruses after administration of intravenous immunoglobulins. To determine the prevalence of hepatitis C virus antibody in intravenous immunoglobulins and protein preparations, 30 commercially available products were tested. Using the Abbott enzyme immunoassay for hepatitis C virus antibody, 27 of 30 (90%) immunoglobulins tested positive. The Ortho immunoassay showed that 28 of 30 (93%) were positive, with one discordant result between the Ortho and Abbott assays. An antigen-blocking or neutralization test (Abbott) confirmed the results of the Ortho assay. Bovine, sheep, goat, and horse sera also were tested before and after isolation of animal immunoglobulins. All results on the animal sera were negative, indicating that the fractionation process did not produce false-positive results. The high prevalence rate of hepatitis C virus antibody in intravenous immunoglobulins has important implications for follow-up of recipients, selection of serum donors, and implementation of anti-hepatitis C virus testing.

Quality-assurance sera (QAS) are prepared from pooled sera composed of thousands of individual donations. Previous studies documented that a substantial percentage of individual QAS test positive for viral disease markers, including antibodies to human immunodeficiency virus and to hepatitis B surface antigen. We tested 239 QAS from various proficiency programs and commercial sources to determine the prevalence of hepatitis C virus (HCV) antibody. We tested samples for anti-HCV by using an enzyme immunoassay (EIA; Abbott Labs.) and an enzyme-linked immunosorbent assay (ELISA; Ortho Diagnostics). We observed an overall positive rate of 49% by one or both assays in all categories of sera tested. In addition, we found a greater rate of positivity (58%) in proficiency program samples than in commercial samples (43%). We found discrepant results between the two assays for 15 of 239 samples (6%). In the discrepant samples, the EIA result was positive, whereas the ELISA result was negative. Anti-HCV positivity in QAS has important implications for laboratory personnel handling these samples.

Lymph node histology and antigen transmission in the nu/nu mouse in response to animal inoculation with Crohn's disease tissue filtrates were re-evaluated. We found that a hyperplastic lymph node response in nu/nu mice occurred with Crohn's disease (CD), ulcerative colitis (UC), or other intestinal disease (OID) tissue inoculations. In addition, antigen transmission to lymph nodes as detected by indirect immunofluorescence using CD sera was observed in all inoculation groups. The immunofluorescent reaction also occurred independently of lymph node histology. Thus, we confirm that CD sera recognize an antigen(s) expressed in lymph nodes of athymic mice inoculated with CD tissue filtrates. The antibody (or antibodies) in CD sera was not specific for this 'CD antigen or antigens', however, as tested in the nu/nu mouse system, because the CD sera antibodies also recognised antigens in UC inoculated and OID inoculated animals.

We have followed up 69 patients who developed non-A, non-B posttransfusion hepatitis in 1972-1978. Chronic hepatitis, defined by biochemical criteria, was observed in 46 patients (67%), the majority of whom subsequently failed to resolve the abnormalities. Chronic hepatitis was a sequela of non-A, non-B posttransfusion hepatitis less often after the blood bank changed to a policy of all volunteer donors. (However, this association may be explained by other coexistent factors.) The alanine aminotransferase level was more likely to be abnormal than the aspartate aminotransferase level during the chronic phase of non-A, non-B posttransfusion hepatitis. By actuarial means it was calculated that the probability of developing normal enzymes after 6-10 yr was 0.47. However, in spite of this high incidence of biochemical disease, virtually all of the patients have remained asymptomatic. Histologic evidence of cirrhosis has been obtained in 4 of these patients, but in only 2 patients at most has clinical evidence of hepatic failure supervened.

Although other investigators have found excellent response rates to the hepatitis B vaccine, we report here an unusually low rate of seroconversion following hepatitis B vaccination in a group of apparently healthy medical center personnel. Only 67% of these individuals developed adequate postvaccination antibodies to HBsAg, in contrast to 85 to 96% in other studies. A significant decrease in seroconversion with increasing age was noted with a 54% seroconversion rate in vaccines over the age of 40; all of whom had received gluteal injections. Employees at another facility had been given deltoid injections from the same vaccine lot and had an overall seroconversion rate of 90%. Subsequently, nonresponders from the first group were revaccinated. Seven of the ten individuals tested developed anti-HBs. We believe the relatively low rate of seroconversion in individuals above the age of 40 may have been related to gluteal injection of the hepatitis B vaccine, and further investigation is warranted.

Sixty-six consecutive liver biopsies demonstrating chronic active hepatitis (CAH) were stained for the presence of HBsAg using the three-step peroxidase-antiperoxidase technique. Only cases of CAH thought to be attributable to either hepatitis B or non-A, non-B hepatitis were included in this series. Twenty-three of 30 biopsies taken from 24 patients with HBsAg-positive serum stained positively. None of the HBsAgsero-negative cases stained positively. Hepatocytes staining positively for HBsAg were generally few in number and randomly distributed within the liver lobules. Three cases of membranous staining were noted.After grading both the degree of inflammatory activity and the amount of HBsAg staining, we found that a statistically significant inverse relationship exists. The biopsies of six of the HBsAg sero-positive patients who had received steroid therapy for their liver disease did not stain differently from the biopsies of the remaining 18 HBsAg sero-positive patients. Stains for HBsAg may help in distinguishing acute hepatitis B (HB) superimposed on preexisting liver disease from hepatitis B-CAH (CAHB). This distinction may be possible because tissue staining almost always is negative in acute HB, whereas it often is focally positive in CAHB. This application of immunopcroxidase may be especially useful in patients who are drug addicts.

The prognostic significance of the HBe-antigen (HBeAg) in the course and outcome of type B hepatitis was studied prospectively in 71 susceptible oncology patients. The patients had been exposed to tumor cell vaccines inadvertently contaminated with hepatitis B surface antigen (HBsAg)-containing plasma. Forty-five patients (63%) were infected. These 45 showed three types of acute seroresponse: HBsAg and HBeAg, 28 patients (62%); HBsAg alone, 8 patients (18%); and a primary antibody to HBsAg (anti-HBs) response, 9 patients (20%). There was no significant difference in acute course and outcome between the two HBs-antigenemic groups. All primary anti-HBs responders had asymptomatic infections. Seventeen patients receiving chemotherapy during the period of hepatitis B exposure were significantly more prone to symptomatic infection with acute HBs-antigenemia, and 2 of these patients developed chronic active hepatitis. The HBeAg is common early in acute hepatitis B among solid tumor patients and at this stage in disease has no prognostic significance independent of HBsAg.

Patients with non-A, non-B post-transfusion hepatitis were followed from the onset of their disease until their blood tests normalized, until they died, or until the present time. Of 66 patients, 30 had a spontaneous resolution of their biochemical disease. Ten patients died or were begun on immunosuppressive therapy with transaminases still abnormal. The remaining 26 patients had abnormal transaminase levels when last seen. By actuarial analysis, only 54% of hepatitis patients are predicted to develop s spontaneous biochemical remission within 3 yr. No further resolutions have occurred after that time, Icteric and anicteric acute disease may be equally likely to progress to chronic disease. Initial and follow-up liver biopsy specimens have revealed both chronic persistent and chronic active hepatitis. Two patients showed histologic evidence of cirrhosis, and a third developed a hepatic coagulopathy and sphenomegaly. No other patient to date, however, has veveloped overt evidence of hepatocellular failure or portal hypertension. Thus, non-A, non-B post-transfusion hepatitis frequently results in biochemical evidence of chronic liver disease, and in a few patients cirrhosis may develop slowly and in a clinically inapparent fashion.