THE JOURNAL OF INFECTIOUS DISEASES. VOL. 137. NO.2.
FEBRUARY 1978
© 1978 by the University of Chicago. All rights reserved. 0022'1899178/3702-0004$01.23
Hepatitis B Immune Globulin: Final Report of a Controlled, Multicenter Trial of Efficacy in Prevention of Dialysis-Associated Hepatitis Alfred M. Prince, Wolf Szmuness, Margaret K. Mann, Girish N. Vyas, George F. Grady, Fred L. Shapiro, Wadi N. Suki, Eli A. Freidman, Morell M. Avram, and Kurt H. Stenzel
The extraordinarily high incidence of hepatitis B virus infection among patients and staff of many renal hemodialysis units[1] has provided an
ideal setting for the evaluation of potential pre· ventive measures. For this reason, a multicenter, randomized, double-blind trial was initiated on
Received for publication April 12, 1977, and in revised form August 26,1977. This study was supported by a contract from the Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. We thank Dr. Robert H. Purcell for hepatitis A antibody determinations, Dr. Blaine Hollinger for determinations of antibody to hepatitis B core antigen, and Ms. Tommie Baker, Ms. Diana Daniels, Mr. Waverly Howard, Ms. Bessie Clinkscale, and Ms. Annie Mae Moffatt for technical assistance. The coordinating center for the study was the Laboratories of Virology and Epidemiology, The Lindsley F. Kimball Research Institute of The New York Blood Center. Dr. Alfred M. Prince was the principal investigator; Dr. Wolf Szmuness the epidemiologist; Ms. Margaret Mann the study coordinator; Ms. Gloria H. Block the consultant statistician; and Mr. Richard Levine, the computer programmer. The locations, participating medical workers, hospitals, and institutional affiliations of the collaborating centers are given in that order. San Francisco: Dr. Girish N. Vyas, Dr. Rudi Schmid, Dr. H. David Watts, and Ms. Linda Quisumbing; Mount Zion Hospital, San Francisco General Hospital, Mills Hospital, Herrick Hospital, Alta Bates Hospital, Franklin Hospital, El Camino Hospital, Sutter Hospital, Stanford Hospital, Parnassus Heights Hospital, and Providence Hospital; University of California Medical Center,
San Francisco. Boston: Dr. George F. Grady, Ms. Judith L. Icuss, and Ms. Katherine Reimherr; Lemuel Shattuck Hospital; Biologic Laboratories, State Laboratory Institute, Massachusetts Department of Public Health; and Tufts University School of Medicine. Minneapolis: Dr. Fred L. Shapiro, Ms. Randi S. Birk, and Ms. Betty Ackerman; Regional Kidney Disease Center, Hennepin County Medical Center, and Sister Kenny Institute and 11 satellite centers; University of Minnesota School of Medicine. Houston: Dr. Wadi N. Suki and Ms. Terhi Lehto; Methodist Hos· pital, Gulf Coast Dialysis Center, Ben Taub General Hospital, and Veterans Administration Hospital; Baylor University College of Medicine. New York: Dr. Eli A. Friedman, Dr. Morrell M. Avram, Dr. Kurt H. Stenzel, Ms. Adeline Josephson, Ms. Gayle Nathanson, and Ms. Claire M. Baumann; Downstate Medical Center, Kings County Hospital, Long Island Hospital, Brooklyn Kidney Center, New York Hospital; State University of New York and Cornell University Medical College. The clinical review panel included Dr. Richard Aach, Washington University School of Medicine, St. Louis, Missouri; Dr. Harvey Alter, National Institutes of Health, Bethesda, Maryland; and Dr. James W. Mosley, University of Southern California School of Medicine, Los Angeles, California. Please address requests for reprints to Dr. Alfred M. Prince, The New York Blood Center, 310 East 67th Street, New York, New York 10021.
131
Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
In a randomized, double-blind multicenter trial, 284 patients and 282 staff members of renal dialysis units who lacked detectable hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) were randomly assigned to receive two 3-ml injections of immune serum globulin with high, intermediate, or low titers of anti-HBs four months apart. The incidence of infection with hepatitis B and of development of HBsAg was significantly lower in both patients and staff who received the high-titer material than in subjects who received the low-titer preparation eight but not 12 months after randomization (P
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To investigate the possibility that decline in potency could have affected the protective effect of the globulin, we determined attack rates for all hepatitis B events for the one- to eight-month period after randomization by the life-table method separately for subjects in the high-titer group who were randomized during the first and second study years. Among patients, attack rates were 8.0% and 6.3% for those randomized in the first and second years, respectively; the corresponding rates for staff were 6.0% and 3.5%. The number of subjects followed for eight months was too few in the third year to permit meaningful analysis. There was thus no indication of a reduction in protective effect associated with the decline in titer of anti-HBs. HBsAg subtypes among treatment groups. HBsAg-positive specimens of serum from 7? subjects could be subtyped. Sixty-two specimens (86%) were ay. The proportions of specimens that were ay from recipients of the norrnal-, intermediate-, and high-titer globulin preparations were 21 (87.5%) of 24, 24 (80%) of 30, and 17 (94.4%) of 18, respectively. There was thus no evidence for a differential effect of the
globulin preparation on different SUbtypes of HBsAg. Persistence of HBsAg among treatment groups. The proportion of subjects in whom persistent antigenemia developed in the three treatment groups is summarized in table 3. The analysis was limited to subjects who developed HBsAg one to eight months after randomization to search for possible effects of the globulin treatments. Persistent antigenemia was defined as detection of HBsAg for at least six months after its appearance and also in the last specimen tested. Persistence of HBsAg was indeterminate if subjects were lost from follow-up before the six-month period had elapsed. Seven (39%) of 18 patients developing HBsAg who received the normal-titer preparation and six (33%) of 18 and two (50%) of four of those who received intermediate- and high-titer preparations, respectively, developed persistent antigenemia. These frequencies did not differ significantly. Among staff, HBsAg persisted in only one of 22 subjects who developed antigen. Among patients receiving the high-titer globulin preparation who developed antigenemia nine
Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
Figure 3. Time of occurrence and categorization of cases of hepatitis among staff of renal dialysis units who were given preparations of immune globulin with high, intermediate, or normal titers of antibody to hepatitis B (HB) surface antigen.
GLOBULIN
Prince et al.
138
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to 12 months after randomization, six of 12 persons developed persistent antigenemia. Persistence of transaminase abnormalities among treatment groups. Figure 5 shows the duration of transaminase elevations in cases of hepatitis B that had their onset in the one- to eight-month period after randomization. Among patients, the mean (± sn) durations of transaminase elevations were 63.8 (± 51.0), 52.3 (± 51.9), and 58.8 (± 59.2) days in recipients of normal-, intermediate-, and high-titer globulin preparations, respectively. Among staff, the corresponding durations were 35.4 (±36.3), 48.4 (± 75.2), and 35.0 (± 13.0) days. The differences among treatment groups were not statistically significant. Analysis of hepatitis B cases occurring in hightiter HBIG recipients one to eight months after randomization. In an attempt to shed light on the occurrence of cases of hepatitis B in high-titer HBIG recipients during the period when significant protection was observed, several aspects of these cases were examined. In all of the cases it
was possible to confirm, on the basis of the appearance of passive anti-HBs three to six days after administration, that the high-titer preparation had actually been administered. Among the five patients with hepatitis B, the interval between initiation of dialysis and receipt of the first HBIG injection averaged 5.6 days (range, zero to 12 days), an interval which was less than the average for all patients in the study (9.9 days). Each of the patients had received blood transfusions (two to seven units) in the six-month period prior to the onset of hepatitis. Among the staff with hepatitis B, the interval between employment and receipt of the first HBIG injection averaged 20.3 days (range, seven to 44 days), an interval which was less than the average for all staff members in the study (29.6 days). None of the three staff members admitted to needle-stick exposures during the period prior to development of hepatitis. Anti-HBs responses one to 12 months aiter randomization. Theoretically, it is possible that passive anti-HBs could depress the primary
Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
Figure 4. Life-table analysis of cumulative attack rates of hepatitis B and/or hepatitis B surface antigen (HBsAg) among staff of renal dialysis units who were given preparations of immune globulin with high, intermediate, or normal titers of antibody to HBsAg. Note the four-month lag in attainment of a 5% attack rate in recipients of the intermediate- (INT.) and hightiter preparations.
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139
Hepatitis B Immune Globulin
Table 3. Persistence of hepatitis B surface antigen (HBsAg) in subjects who received preparations of immune globulin with high, intermediate, or normal titers of antibody to HBsAg and in whom HBsAg developed one to eight months after randomization. No. with HBsAg Group, preparation Patients Normal-titer Intermediate-titer High-titer
Total
Persistent
(%)
Indeterminate
8 9 1
7 (39) 6 (33) 2 (50)
3 3 1
18
15 (37)
7
8 7 4
0 1 (11) 0
1 1 0
1 (4)
2
19
NOTE. Persistent antigenemia was defined as detection of HBsAg for at least six months after its appearance and also in the last specimen tested. Persistence was indeterminate if subjects were lost from follow-up before the end of six months.
anti-HBs response. We therefore analyzed the anti-HBs response in those subjects who developed hepatitis or nonpersistent HBs antigenemia. Altogether, 86% of patients and 90% of employees had a primary anti-HBs response detectable by solid-phase RIA. As shown in table 4, there was no significant difference in the proportion of subjects who seroconverted in the three treatment groups, in peak antibody responses as
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Figure 5. Duration of transaminase elevations (>2.5 times the upper limit of normal [ULN]) in patients and staff of renal dialysis units who received preparations of immune globulin with high, intermediate, or normal titers of antibody to hepatitis B surface antigen (HBsAg) and who developed hepatitis B or HBsAg one to eight months after randomization.
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Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
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semiquantitatively expressed in Ausab ratio units, in the interval between disappearance of HBsAg and appearance of anti-HBs, or in the interval between the appearance of anti-HBs and attainment of peak titers. To assess further the effect of exogenous antiHBs on the primary anti-HBs response and also to assess the frequency of possible passive-active immunization, we tested the 12-month follow-up samples of serum from all subjects who did not develop hepatitis or HBsAg for anti-HBs by RIA. Serial samples of sera from all subjects with antiHBs in their 12-month specimen were then tested to determine peak responses and their time of occurrence. Seroconversion for anti-HBs without hepatitis or appearance of HBsAg was noted in 10 (5.3%) of 187 patients and in 24 (16.4%) of 146 staff members followed for at least 12 months. If subjects who received high-titer HBIG and experienced protection against hepatitis developed subclinical infections (i.e., passive-active immunization occurred), an excess of seroconversions would be expected in the high-titer group. As summarized in table 5, this was not the case. Among both patients and staff, there were fewer "seroconversions in the high-titer HBIG recipients than in the recipients of the normal-titer preparation. There was no significant difference in the intensity or the timing of the anti-HBs response as a function of treatment group. The cumulative incidence of all of the tested
Prince et al.
140
Table 4. Seroconversion for antibody (anti-HBs) to hepatitis B surface antigen (HBsAg) in patients and staff of renal dialysis units who received preparations of immune globulin with high, intermediate, or normal titers of anti-HBs and who developed hepatitis B one to 12 months after randomization.
Group, preparation
No. seroconverting (%)
Peak titer of anti-HBst
Days between last HBsAg-positive spe- Days between cimen and first onset of anti-HBs anti-HBs response and peak titer
8 9 4
6 (75) 8 (89) 4 (100)
86 ±80 74 ±91 120 ± 78
-19 ± 57 10 ± 53 12 ± 7
46 ±48 88 ± 107 120 ± 59
10 17 4
9 (90) 15 (88) 4 (100)
79 ±38 73 ±61 122 ± 162
89 ±64 58 ±39 65 ± 75
101 ± 60 86 ± 57 95 ± 39
NOTE. Unless otherwise indicated, data are means ± SD • *Cases with HBsAg in the last specimen were excluded. t Ausab ratio units (Ausab,® Abbott Laboratories, North Chicago, IlL).
indicators of hepatitis B infection at 12 months in the three treatment groups is summarized in table 6. Among staff, the incidence of all types of hepatitis B infection was significantly lower in those who received high-titer HBIG than in those who received normal- or intermediate-titer preparations (normal titer vs, high titer, P = 0.014; intermediate vs. high, P
FEBRUARY 1978
© 1978 by the University of Chicago. All rights reserved. 0022'1899178/3702-0004$01.23
Hepatitis B Immune Globulin: Final Report of a Controlled, Multicenter Trial of Efficacy in Prevention of Dialysis-Associated Hepatitis Alfred M. Prince, Wolf Szmuness, Margaret K. Mann, Girish N. Vyas, George F. Grady, Fred L. Shapiro, Wadi N. Suki, Eli A. Freidman, Morell M. Avram, and Kurt H. Stenzel
The extraordinarily high incidence of hepatitis B virus infection among patients and staff of many renal hemodialysis units[1] has provided an
ideal setting for the evaluation of potential pre· ventive measures. For this reason, a multicenter, randomized, double-blind trial was initiated on
Received for publication April 12, 1977, and in revised form August 26,1977. This study was supported by a contract from the Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. We thank Dr. Robert H. Purcell for hepatitis A antibody determinations, Dr. Blaine Hollinger for determinations of antibody to hepatitis B core antigen, and Ms. Tommie Baker, Ms. Diana Daniels, Mr. Waverly Howard, Ms. Bessie Clinkscale, and Ms. Annie Mae Moffatt for technical assistance. The coordinating center for the study was the Laboratories of Virology and Epidemiology, The Lindsley F. Kimball Research Institute of The New York Blood Center. Dr. Alfred M. Prince was the principal investigator; Dr. Wolf Szmuness the epidemiologist; Ms. Margaret Mann the study coordinator; Ms. Gloria H. Block the consultant statistician; and Mr. Richard Levine, the computer programmer. The locations, participating medical workers, hospitals, and institutional affiliations of the collaborating centers are given in that order. San Francisco: Dr. Girish N. Vyas, Dr. Rudi Schmid, Dr. H. David Watts, and Ms. Linda Quisumbing; Mount Zion Hospital, San Francisco General Hospital, Mills Hospital, Herrick Hospital, Alta Bates Hospital, Franklin Hospital, El Camino Hospital, Sutter Hospital, Stanford Hospital, Parnassus Heights Hospital, and Providence Hospital; University of California Medical Center,
San Francisco. Boston: Dr. George F. Grady, Ms. Judith L. Icuss, and Ms. Katherine Reimherr; Lemuel Shattuck Hospital; Biologic Laboratories, State Laboratory Institute, Massachusetts Department of Public Health; and Tufts University School of Medicine. Minneapolis: Dr. Fred L. Shapiro, Ms. Randi S. Birk, and Ms. Betty Ackerman; Regional Kidney Disease Center, Hennepin County Medical Center, and Sister Kenny Institute and 11 satellite centers; University of Minnesota School of Medicine. Houston: Dr. Wadi N. Suki and Ms. Terhi Lehto; Methodist Hos· pital, Gulf Coast Dialysis Center, Ben Taub General Hospital, and Veterans Administration Hospital; Baylor University College of Medicine. New York: Dr. Eli A. Friedman, Dr. Morrell M. Avram, Dr. Kurt H. Stenzel, Ms. Adeline Josephson, Ms. Gayle Nathanson, and Ms. Claire M. Baumann; Downstate Medical Center, Kings County Hospital, Long Island Hospital, Brooklyn Kidney Center, New York Hospital; State University of New York and Cornell University Medical College. The clinical review panel included Dr. Richard Aach, Washington University School of Medicine, St. Louis, Missouri; Dr. Harvey Alter, National Institutes of Health, Bethesda, Maryland; and Dr. James W. Mosley, University of Southern California School of Medicine, Los Angeles, California. Please address requests for reprints to Dr. Alfred M. Prince, The New York Blood Center, 310 East 67th Street, New York, New York 10021.
131
Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
In a randomized, double-blind multicenter trial, 284 patients and 282 staff members of renal dialysis units who lacked detectable hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) were randomly assigned to receive two 3-ml injections of immune serum globulin with high, intermediate, or low titers of anti-HBs four months apart. The incidence of infection with hepatitis B and of development of HBsAg was significantly lower in both patients and staff who received the high-titer material than in subjects who received the low-titer preparation eight but not 12 months after randomization (P
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MONTHS AFTER RANDOMIZATION
To investigate the possibility that decline in potency could have affected the protective effect of the globulin, we determined attack rates for all hepatitis B events for the one- to eight-month period after randomization by the life-table method separately for subjects in the high-titer group who were randomized during the first and second study years. Among patients, attack rates were 8.0% and 6.3% for those randomized in the first and second years, respectively; the corresponding rates for staff were 6.0% and 3.5%. The number of subjects followed for eight months was too few in the third year to permit meaningful analysis. There was thus no indication of a reduction in protective effect associated with the decline in titer of anti-HBs. HBsAg subtypes among treatment groups. HBsAg-positive specimens of serum from 7? subjects could be subtyped. Sixty-two specimens (86%) were ay. The proportions of specimens that were ay from recipients of the norrnal-, intermediate-, and high-titer globulin preparations were 21 (87.5%) of 24, 24 (80%) of 30, and 17 (94.4%) of 18, respectively. There was thus no evidence for a differential effect of the
globulin preparation on different SUbtypes of HBsAg. Persistence of HBsAg among treatment groups. The proportion of subjects in whom persistent antigenemia developed in the three treatment groups is summarized in table 3. The analysis was limited to subjects who developed HBsAg one to eight months after randomization to search for possible effects of the globulin treatments. Persistent antigenemia was defined as detection of HBsAg for at least six months after its appearance and also in the last specimen tested. Persistence of HBsAg was indeterminate if subjects were lost from follow-up before the six-month period had elapsed. Seven (39%) of 18 patients developing HBsAg who received the normal-titer preparation and six (33%) of 18 and two (50%) of four of those who received intermediate- and high-titer preparations, respectively, developed persistent antigenemia. These frequencies did not differ significantly. Among staff, HBsAg persisted in only one of 22 subjects who developed antigen. Among patients receiving the high-titer globulin preparation who developed antigenemia nine
Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
Figure 3. Time of occurrence and categorization of cases of hepatitis among staff of renal dialysis units who were given preparations of immune globulin with high, intermediate, or normal titers of antibody to hepatitis B (HB) surface antigen.
GLOBULIN
Prince et al.
138
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to 12 months after randomization, six of 12 persons developed persistent antigenemia. Persistence of transaminase abnormalities among treatment groups. Figure 5 shows the duration of transaminase elevations in cases of hepatitis B that had their onset in the one- to eight-month period after randomization. Among patients, the mean (± sn) durations of transaminase elevations were 63.8 (± 51.0), 52.3 (± 51.9), and 58.8 (± 59.2) days in recipients of normal-, intermediate-, and high-titer globulin preparations, respectively. Among staff, the corresponding durations were 35.4 (±36.3), 48.4 (± 75.2), and 35.0 (± 13.0) days. The differences among treatment groups were not statistically significant. Analysis of hepatitis B cases occurring in hightiter HBIG recipients one to eight months after randomization. In an attempt to shed light on the occurrence of cases of hepatitis B in high-titer HBIG recipients during the period when significant protection was observed, several aspects of these cases were examined. In all of the cases it
was possible to confirm, on the basis of the appearance of passive anti-HBs three to six days after administration, that the high-titer preparation had actually been administered. Among the five patients with hepatitis B, the interval between initiation of dialysis and receipt of the first HBIG injection averaged 5.6 days (range, zero to 12 days), an interval which was less than the average for all patients in the study (9.9 days). Each of the patients had received blood transfusions (two to seven units) in the six-month period prior to the onset of hepatitis. Among the staff with hepatitis B, the interval between employment and receipt of the first HBIG injection averaged 20.3 days (range, seven to 44 days), an interval which was less than the average for all staff members in the study (29.6 days). None of the three staff members admitted to needle-stick exposures during the period prior to development of hepatitis. Anti-HBs responses one to 12 months aiter randomization. Theoretically, it is possible that passive anti-HBs could depress the primary
Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
Figure 4. Life-table analysis of cumulative attack rates of hepatitis B and/or hepatitis B surface antigen (HBsAg) among staff of renal dialysis units who were given preparations of immune globulin with high, intermediate, or normal titers of antibody to HBsAg. Note the four-month lag in attainment of a 5% attack rate in recipients of the intermediate- (INT.) and hightiter preparations.
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139
Hepatitis B Immune Globulin
Table 3. Persistence of hepatitis B surface antigen (HBsAg) in subjects who received preparations of immune globulin with high, intermediate, or normal titers of antibody to HBsAg and in whom HBsAg developed one to eight months after randomization. No. with HBsAg Group, preparation Patients Normal-titer Intermediate-titer High-titer
Total
Persistent
(%)
Indeterminate
8 9 1
7 (39) 6 (33) 2 (50)
3 3 1
18
15 (37)
7
8 7 4
0 1 (11) 0
1 1 0
1 (4)
2
19
NOTE. Persistent antigenemia was defined as detection of HBsAg for at least six months after its appearance and also in the last specimen tested. Persistence was indeterminate if subjects were lost from follow-up before the end of six months.
anti-HBs response. We therefore analyzed the anti-HBs response in those subjects who developed hepatitis or nonpersistent HBs antigenemia. Altogether, 86% of patients and 90% of employees had a primary anti-HBs response detectable by solid-phase RIA. As shown in table 4, there was no significant difference in the proportion of subjects who seroconverted in the three treatment groups, in peak antibody responses as
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Figure 5. Duration of transaminase elevations (>2.5 times the upper limit of normal [ULN]) in patients and staff of renal dialysis units who received preparations of immune globulin with high, intermediate, or normal titers of antibody to hepatitis B surface antigen (HBsAg) and who developed hepatitis B or HBsAg one to eight months after randomization.
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Downloaded from http://jid.oxfordjournals.org/ at University of New South Wales on July 27, 2015
Total Staff Normal-titer Interrnediate-ti ter High-titer
Not persistent
semiquantitatively expressed in Ausab ratio units, in the interval between disappearance of HBsAg and appearance of anti-HBs, or in the interval between the appearance of anti-HBs and attainment of peak titers. To assess further the effect of exogenous antiHBs on the primary anti-HBs response and also to assess the frequency of possible passive-active immunization, we tested the 12-month follow-up samples of serum from all subjects who did not develop hepatitis or HBsAg for anti-HBs by RIA. Serial samples of sera from all subjects with antiHBs in their 12-month specimen were then tested to determine peak responses and their time of occurrence. Seroconversion for anti-HBs without hepatitis or appearance of HBsAg was noted in 10 (5.3%) of 187 patients and in 24 (16.4%) of 146 staff members followed for at least 12 months. If subjects who received high-titer HBIG and experienced protection against hepatitis developed subclinical infections (i.e., passive-active immunization occurred), an excess of seroconversions would be expected in the high-titer group. As summarized in table 5, this was not the case. Among both patients and staff, there were fewer "seroconversions in the high-titer HBIG recipients than in the recipients of the normal-titer preparation. There was no significant difference in the intensity or the timing of the anti-HBs response as a function of treatment group. The cumulative incidence of all of the tested
Prince et al.
140
Table 4. Seroconversion for antibody (anti-HBs) to hepatitis B surface antigen (HBsAg) in patients and staff of renal dialysis units who received preparations of immune globulin with high, intermediate, or normal titers of anti-HBs and who developed hepatitis B one to 12 months after randomization.
Group, preparation
No. seroconverting (%)
Peak titer of anti-HBst
Days between last HBsAg-positive spe- Days between cimen and first onset of anti-HBs anti-HBs response and peak titer
8 9 4
6 (75) 8 (89) 4 (100)
86 ±80 74 ±91 120 ± 78
-19 ± 57 10 ± 53 12 ± 7
46 ±48 88 ± 107 120 ± 59
10 17 4
9 (90) 15 (88) 4 (100)
79 ±38 73 ±61 122 ± 162
89 ±64 58 ±39 65 ± 75
101 ± 60 86 ± 57 95 ± 39
NOTE. Unless otherwise indicated, data are means ± SD • *Cases with HBsAg in the last specimen were excluded. t Ausab ratio units (Ausab,® Abbott Laboratories, North Chicago, IlL).
indicators of hepatitis B infection at 12 months in the three treatment groups is summarized in table 6. Among staff, the incidence of all types of hepatitis B infection was significantly lower in those who received high-titer HBIG than in those who received normal- or intermediate-titer preparations (normal titer vs, high titer, P = 0.014; intermediate vs. high, P
