Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992), pp. 1245-1249
Response to Hepatitis B Vaccination by Liver Transplant Candidates DAVID H. VAN THIEL, MD, LOBNA EL-ASHMAWY, MD, KRISTIN LOVE, BS, JUDITH S. GAVALER, PhD, and THOMAS E. STARZL, MD, PhD
Liver transplantation (OLTx) is a procedure offered to individuals with advanced liver disease who are expected to live less than a year. Despite improvement in the care of transplant recipients, these patients are exposed to large volumes of blood and, as a result, are at risk to acquire hepatitis. Currently, the only vaccines available for the prevention of hepatitis are those that induce a response to HB~Ag. In this study, 144 patients awaiting OLTx and 15 controls were vaccinated three times, once a month, intramuscularly in the deltoid using the Merck Hepatovax plasma-derived vaccine. This schedule was continued regardless of whether or not OLTx occurred before the series was completed. For the 15 controls, the response rate was 93% and for individuals with end-stage liver disease, it ranged from 44 to 54% (P < 0.004). No difference in the percentage of those developing antibody was detected between groups based upon disease indication or whether the vaccination series was completed before or after OLTx. Of the following: WBC, lymphocytes (percent and number), CD3+ cells (percent and number), CD4+ cells (percent and number), CD8+ cells (percent and number), CD4+/ CD8+ ratio, and B cells (percent and number), only the absolute WBC (P < 0.05) distinguished between those who did and did not develop antibody. These data suggest: (1) those with chronic liver disease respond less well to Hepatovax than do controls; (2) a rapid sequence of vaccinations is capable of producing antibody in normals and those with liver disease; (3) no difference is evident between those who completed their vaccination schedule before or after OLTx; and (4) among patients with chronic advanced liver disease, a higher total WBC is associated with an increased rate of seroconversion. KEY WORDS: fiver transplantation; hepatitis B vaccination; seroconversion.
Hepatitis B virus (HBV) infection occurs worldwide and is a common cause of clinically important liver disease (1, 2). HBV can cause fulminant, subfulminant, or chronic hepatitis; cirrhosis; and/or hepatoma in infected individuals. Each of these conditions can be an indication for orthotopic liver transplantation (OLTx) (3). In an attempt to reduce Manuscript received August 15, 1990; revised manuscript received January 20, 1992; accepted February 3, 1992. From the Department of Surgery, the Division of Gastroenterology, and the Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261. Address for reprint requests: Dr. David H. Van Thiel, 3601 Fifth Avenue, Falk Clinic 5C, Pittsburgh, Pennsylvania 15213.
the prevalence of HBV infection, vaccination programs have been initiated in various high-risk groups including homosexuals, children born to hepatitis B virus carders, physicians and hospital personnel exposed to blood and blood products as part of their work, dialysis patients, and hemophiliacs (4-20). In general, vaccination programs have been quite successful and result in antibody production in 90-95% of vaccinated normal individuals (4, 9, 10, 13, 14, 16, 17). Certain groups ofimmunosuppressed individuals, either because of a disease process or therapy directed at their disease process, have shown poorer responses to hepatitis B vacci-
Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
0163-2116/92/0800-1245506.50/09 1992PlenumPublishingCorporation
1245
VAN THIEL ET AL nation than those seen in the normal population (8, 10-12, 15, 16, 18-20). Examples include individuals who are uremic and aged or HIV-positive individuals, and those receiving chemotherapy for cancer. The response to HBV vaccination by individuals selected for OLT x because of chronic liver disease has not yet been reported. Herein we report an experience with HBV vaccination in a liver transplant candidate population. M A T E R I A L S AND M E T H O D S Subjects. A total of 144 individuals selected for orthotopic liver transplantation because of chronic liver disease who were negative for HB s antigen, HBs antibody, and HBc antibody were selected for study. Each received three monthly injections of 1 cc Hepatovax in the deltoid muscle and were assessed for their antibody response to vaccination one month after the third injection. Controls. A total of 15 individuals including research laboratory personnel and fellows in gastroenterology served as controls for this study. None had any identifiable disease, and all were medication-free at the time of study. Their ages ranged from 25 to 51. Each was immunized with 1 cc of Hepatovax, which was administered intramuscularly into the deltoid muscle as three consecutive monthly injections in a manner similar to that used for the study population. All were HBs antigen, HBc antibody, and HB~ antibody negative prior to being immunized. Hepatitis B Surface Antigen (HB~Ag) and Antibody (HBsAb) Testing. Commercial kits for HBsAg and HBsAb obtained from Abbott Laboratories were used to detect HBsAg, HBsAh, and HBcAb respectively in the subjects studied. All tests were run in duplicate using the technique recommended by the manufacturer. A positive response for HB~Ab following vaccination was defined as a signal-to-noise ratio of greater than 10 using the Abbott HBs antibody kit. Statistical Analysis. The Student's t test was used to study the differences between the means of two groups. Chi-square analysis was used to evaluate associations and differences between proportions. A P value
Response to Hepatitis B Vaccination by Liver Transplant Candidates DAVID H. VAN THIEL, MD, LOBNA EL-ASHMAWY, MD, KRISTIN LOVE, BS, JUDITH S. GAVALER, PhD, and THOMAS E. STARZL, MD, PhD
Liver transplantation (OLTx) is a procedure offered to individuals with advanced liver disease who are expected to live less than a year. Despite improvement in the care of transplant recipients, these patients are exposed to large volumes of blood and, as a result, are at risk to acquire hepatitis. Currently, the only vaccines available for the prevention of hepatitis are those that induce a response to HB~Ag. In this study, 144 patients awaiting OLTx and 15 controls were vaccinated three times, once a month, intramuscularly in the deltoid using the Merck Hepatovax plasma-derived vaccine. This schedule was continued regardless of whether or not OLTx occurred before the series was completed. For the 15 controls, the response rate was 93% and for individuals with end-stage liver disease, it ranged from 44 to 54% (P < 0.004). No difference in the percentage of those developing antibody was detected between groups based upon disease indication or whether the vaccination series was completed before or after OLTx. Of the following: WBC, lymphocytes (percent and number), CD3+ cells (percent and number), CD4+ cells (percent and number), CD8+ cells (percent and number), CD4+/ CD8+ ratio, and B cells (percent and number), only the absolute WBC (P < 0.05) distinguished between those who did and did not develop antibody. These data suggest: (1) those with chronic liver disease respond less well to Hepatovax than do controls; (2) a rapid sequence of vaccinations is capable of producing antibody in normals and those with liver disease; (3) no difference is evident between those who completed their vaccination schedule before or after OLTx; and (4) among patients with chronic advanced liver disease, a higher total WBC is associated with an increased rate of seroconversion. KEY WORDS: fiver transplantation; hepatitis B vaccination; seroconversion.
Hepatitis B virus (HBV) infection occurs worldwide and is a common cause of clinically important liver disease (1, 2). HBV can cause fulminant, subfulminant, or chronic hepatitis; cirrhosis; and/or hepatoma in infected individuals. Each of these conditions can be an indication for orthotopic liver transplantation (OLTx) (3). In an attempt to reduce Manuscript received August 15, 1990; revised manuscript received January 20, 1992; accepted February 3, 1992. From the Department of Surgery, the Division of Gastroenterology, and the Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261. Address for reprint requests: Dr. David H. Van Thiel, 3601 Fifth Avenue, Falk Clinic 5C, Pittsburgh, Pennsylvania 15213.
the prevalence of HBV infection, vaccination programs have been initiated in various high-risk groups including homosexuals, children born to hepatitis B virus carders, physicians and hospital personnel exposed to blood and blood products as part of their work, dialysis patients, and hemophiliacs (4-20). In general, vaccination programs have been quite successful and result in antibody production in 90-95% of vaccinated normal individuals (4, 9, 10, 13, 14, 16, 17). Certain groups ofimmunosuppressed individuals, either because of a disease process or therapy directed at their disease process, have shown poorer responses to hepatitis B vacci-
Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
0163-2116/92/0800-1245506.50/09 1992PlenumPublishingCorporation
1245
VAN THIEL ET AL nation than those seen in the normal population (8, 10-12, 15, 16, 18-20). Examples include individuals who are uremic and aged or HIV-positive individuals, and those receiving chemotherapy for cancer. The response to HBV vaccination by individuals selected for OLT x because of chronic liver disease has not yet been reported. Herein we report an experience with HBV vaccination in a liver transplant candidate population. M A T E R I A L S AND M E T H O D S Subjects. A total of 144 individuals selected for orthotopic liver transplantation because of chronic liver disease who were negative for HB s antigen, HBs antibody, and HBc antibody were selected for study. Each received three monthly injections of 1 cc Hepatovax in the deltoid muscle and were assessed for their antibody response to vaccination one month after the third injection. Controls. A total of 15 individuals including research laboratory personnel and fellows in gastroenterology served as controls for this study. None had any identifiable disease, and all were medication-free at the time of study. Their ages ranged from 25 to 51. Each was immunized with 1 cc of Hepatovax, which was administered intramuscularly into the deltoid muscle as three consecutive monthly injections in a manner similar to that used for the study population. All were HBs antigen, HBc antibody, and HB~ antibody negative prior to being immunized. Hepatitis B Surface Antigen (HB~Ag) and Antibody (HBsAb) Testing. Commercial kits for HBsAg and HBsAb obtained from Abbott Laboratories were used to detect HBsAg, HBsAh, and HBcAb respectively in the subjects studied. All tests were run in duplicate using the technique recommended by the manufacturer. A positive response for HB~Ab following vaccination was defined as a signal-to-noise ratio of greater than 10 using the Abbott HBs antibody kit. Statistical Analysis. The Student's t test was used to study the differences between the means of two groups. Chi-square analysis was used to evaluate associations and differences between proportions. A P value
