Hepatitis B Immune Globulin for Accidental Exposures among Medical Personnel: Final Report of a Multicenter Controlled Trial

Medical personnel accidentally exposed to blood from patients who had acute hepatitis or carried hepatitis B surface antigen (HBsAg) were assigned randomly to receive two injections one month apart of immune serum globulin containing a high titer of antibody to HBsAg (anti-HBs) (269 subjects), an intermediate titer (223 subjects), or a normal titer (265 subjects). Four months after exposure nearly 7% of recipients of normal-titer globulin or intermediate-titer globulin had developed hepatitis B, whereas no cases had appeared among recipients of high-titer globulin (P < 0.01). However, an excess of late-onset cases in recipients of high-titer globulin nullified initial evidence of protection; at follow-up at nine months, the cumulative incidence of hepatitis B had reached 8.7%, 7.3%, and 7.2%, respectively, in the three groups (P > 0.30). Intercurrent infection was estimated to have accounted for only 20% of late-onset cases; 80% were thought to reflect an effect of high-titer globulin which was sufficient to delay onset but insufficient to reduce clinical severity. Many of these cases emerged in the presence of anti-HBs residual from administration of hightiter globulin, whereas no cases occurred in individuals who already possessed minimal amounts of anti-HBs at the time of exposure. The high-titer globulin was found to contain fragmented anti-HBs which may have interfered with the neutralizing activity of the large amount of unfragmented anti-HBs also present in the high-titer globulin. In any event, the lack of significant protection in the current trial means that a decision to use high-titer globulin as postexposure prophylaxis will have to rest upon the evidence of protection that has been obtained by others.