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Vaccination of Patients With Liver Disease: Who, When, and How

Vol. 4, Issue 2, pp. 185-187, March 1998


D. H. Van Thiel

From the Division of Gastroenterology, Department of Medicine, Loyola University Medical Center, Maywood, IL.

Hepatitis B infection continues to be a common cause of acute hepatitis in the United States. More than one third (34%) of all cases of acute hepatitis reported to the U.S. Center for Disease Control (CDC) annually are due to Hepatitis B virus (HBV).1 Thus, an estimated 300,000 new cases of acute HBV infection occur annually. Twenty percent of these cases become chronic (40,000 cases/year),2 A minority of these progress to cirrhosis (15,000), and 3,000 to 5,000 develop hepatocellular cancer.2

The vast majority of these infections occur in young adults as a consequence of either intravenous drug use or sexual activity.3 With current blood donor screening practices, only a minority of cases occur as a consequence of blood transfusion.4 Even fewer cases occur as a consequence of solid organ transplantation,5 and the vast majority of these occur as a consequence of the use of an isolated Hepatitis B core antibody (HBcAb)-positive allograft6 in a Hepatitis B surface antibody (HBsAb)-negative recipient.

In contrast to the relatively low rate of disease chronicity (20%) and slow progression (10 to 30 years) that is seen in immunocompetent individuals, the rate of disease chronicity is nearly universal, and the rate of disease progression to cirrhosis and hepatocellular carcinoma is rapid and can occur as fast as 1 year in liver transplant recipients, who are HBsAg positive.7,8 As a result, many centers do not provide and most insurers do not indemnify liver transplantation in individuals who are HBsAg positive.

The fact that so many, estimated to be between a minimum of 4,000 to as many as 30,000 to 40,000, could benefit from liver transplantation each year if the indications for transplantation were liberalized to include individuals with alcoholism, HBV infection, and hepatic cancer, mandates that every effort should be made to use every potential donor organ made available for transplantation.

Vaccination against HBV in individuals awaiting liver transplantation has the potential of not only preventing subsequent HBV infection in such individuals but also enabling the use of isolated HBcAb-positive donor organs with little or no risk of HBV infection in the recipients of such organs. The potential benefit of successful vaccination of individuals with chronic renal disease, because of the number of individuals involved and donor organs available, would be even greater than that experienced by liver transplant candidates and recipients should an effective vaccination response be achievable. Unfortunately, the response rate to HBV vaccination of individuals awaiting liver transplantation as reported by Chalasani et al9 in the present issue of Liver Transplantation and Surgery is quite poor (16%) compared with that achieved in most healthy populations, where the response rate is much greater.9a The same poor response to HBV vaccination as seen in potential liver transplant recipients has been reported to occur in individuals with chronic renal disease awaiting renal transplantation.10-12

Chalasani et al9 report further that the response to HBV vaccination after successful liver transplantation (6.7%) is even less than that experienced in candidates awaiting liver transplants (16%). Not unexpectedly, because of the overall better health status of those with cholestatic liver disease and the relative abundance in this population of females, who are known to respond better to HBV vaccination and infection compared with males, the response rate of individuals awaiting liver transplantation with cholestatic disease (43%) was noted to be considerably greater than that experienced by individuals with parenchymal liver disease.

Based upon these data, Chalasani et al9 raise the serious question as to whether or not HBV vaccination of individuals awaiting liver transplantation should be continued. They argue that because the de novo risk of HBV disease in such individuals is so low (2.3%), HBV vaccination might reasonably be discontinued in such cases. Nonetheless, they end their report with the statement that should vaccination be continued, additional studies with the goal of determining the optimal dose and vaccination schedules are necessary.

My own experience at three different transplant centers (Pittsburgh, Oklahoma, and Kentucky) confirms the findings of Chalasani et al.13 Rather than despair of reaching the goal of successful vaccination in potential transplant recipients, I believe two different approaches should be advanced. The first and most likely to achieve immediate benefit would be to do as Chalasani et al9 suggest and determine the best dose and vaccination schedule available for potential allograft recipients. This approach might reasonably incorporate the use of adjuvants, such as interferon, thymosin 1, or levamisole, as primers of the immune system before or concurrently with the administration of the vaccine. Obviously, the use of such adjuvants with vaccines needs to be tested in trials.

A potentially more effective approach, albeit one that will see benefit only years from now, would be to vaccinate all adults with clinical liver disease, regardless of its severity, as soon as it is identified so as to induce protection while their immune responses are still functional rather than waiting until a consideration for transplantation becomes obvious and their immune system is compromised. This latter approach could ideally be extended to universal vaccination of young adults in an effort to eliminate Hepatitis B as a disease process of clinical importance in the United States. Clearly, universal vaccination of infants as recommended by the American Academy of Pediatrics is the logical extension of such an approach.14 Unfortunately, the benefits of this latter approach will require a decade or more to be manifested clinically.

A program that would likely produce clinical benefit in a time frame half as long or even less would be to encourage all generalists and internists, and gastroenterologists, hepatologists, and nephrologists for that matter, to vaccinate individuals with clinical liver or renal disease against HBV and Hepatitis A virus infections. Such an approach would likely increase markedly the frequency of anti-Hepatitis B surface antigen (HBsAg) positivity in future potential recipients of solid organ transplants, reduce the risk of de novo infection, and enable the use of isolated HBcAb-positive donor organs in recipients, who are anti-HBsAg positive.

Measles, mumps, polio, diphtheria, tetanus, and pertussis vaccinations have for all practical purposes eliminated these disease conditions in the United States.15-17 The application of widespread HBV vaccination has the potential to do the same for HBV. Should this be accomplished, the number of allograft candidates who are HBV positive would be reduced, if not eliminated, and the population of isolated HBsAb-positive donors, as opposed to isolated HBc-Ab donors, would be expanded for the benefit of all.

Table of Contents


Address reprint requests to D.H. Van Thiel, MD, 2160 South First Avenue, Building 114, Room 54, Maywood, IL 60153.


1. Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am 1994;23:437-455 [ Link previously at www.ncbi.nlm.nih.gov ].

2. Seeff L, Koff RS. Evolving concepts of the clinical and serologic consequence of Hepatitis B virus infection. Semin Liver Dis 1986;6:11-22[ Medline].

3. Stremmel W, Schwarzendrube J, Nederau C, Strohmeyer G. Epidermology, clinical course, and treatment of chronic viral hepatitis. Hepatogastroenterology 1991;31:21-24.

4. Hoofnagle JH, Seeff LB, Bales ZB, Zimmerman HJ. Type B hepatitis after transfusion with blood containing antibody to Hepatitis B core antibody. N Engl J Med 1978;298:1379 [ Link previously at www.ncbi.nlm.nih.gov ].

5. Douglas DD, Rakela J, Mamish D, Wright TL, Krom RAF, Weisner RH. Transmission of Hepatitis B virus (HBV) infection from orthotopic donor livers. Hepatology 1992;16:49a.

6. Wachs ME, Amend WJ, Ascher NL, Bretan PN, Emond J, Lake JR, et al. The risk of transmission of Hepatitis B from HBsAg negative, HBcAb positive, HBIgM negative organ donors. Transplantation 1995;59:230-234 [ Link previously at www.ncbi.nlm.nih.gov ].

7. Samuel D, Alexander G. Liver transplantation for Hepatitis B virus infection. Liver Transpl Surg 1995;1:270-274 [ Link previously at www.ncbi.nlm.nih.gov ].

8. Todo S, Demetris AJ, Van Thiel DH, Tepperman L, Fung JJ, Starzl TE. Orthotopic liver transplantation in patients with Hepatitis B virus related liver disease. Hepatology 1991;13:619-626[ Abstract].

9. Chalasani N, Smallwood G, Halcomb J, Fried MW, Boyer TD. Is vaccination against Hepatitis B infection indicated in patients waiting for or following orthotopic liver transplantation? Liver Transpl Surg 128-132.

9a. Hadler SC, Francis DP, Maynard JE, Thompson SE, Judson FN, Echenberg DF, et al. Long-term immunogenicity and efficacy of Hepatitis B vaccine in homosexual males. N Engl J Med 1986;315:209-214[ Medline].

10. Johnson DW, Fleming SJ. The use of vaccines in renal failure. Clin Pharmacokinet 1992;22:434-446[ Link previously at www.ncbi.nlm.nih.gov ].

11. Stevens CE, Alter HJ, Taylor PE, Zang EA, Harley EJ, Szmuness W, the Dialysis Vaccine Trial Study Group. Hepatitis B vaccine in patients receiving hemodialysis: Immunogenicity and efficacy. N Engl J Med 1984;311:496-501 [ Link previously at www.ncbi.nlm.nih.gov ].

12. Crosnier J, Junger P, Courouce AM, Laplanche A, Benhamou E, Degos F, et al. Randomized placebo controlled trial of Hepatitis B surface antigen vaccine in French hemodialysis units: II. Hemodialysis patients. Lancet 1981;1:797-800 [ Link previously at www.ncbi.nlm.nih.gov ].

13. Van Thiel DH, El-Ashmawy L, Love K, Gavaler JS, Starzl TE. Response to Hepatitis B vaccination by liver transplant candidates. Dig Dis Sci 1992;37:1245-1249 [ Link previously at www.ncbi.nlm.nih.gov ].

14. Hepatitis B virus: A comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: Recommendations of the immunization practices advisory committee (ACIP). MMWR 1991;40 (RR-13):1-19.

15. MeaslesUnited States, 1996 and the interruption of indigenous transmission. MMWR 1997;46:242-246 [ Link previously at www.ncbi.nlm.nih.gov ].

16. Noker DJ, Swinton J. Vaccination in pulses: A strategy for global eradication of measles and polio. Trends in Microbiology 1997;5:14-19 [ Link previously at www.ncbi.nlm.nih.gov ].

17. de Quadros CA, Hersh BS, Olive JM, Andras JK, da Silveira CM, Carrasco PA. Eradication of wild polio virus from the Americas: Acute flaccid paralysis surveillance 1988-1995. J Infect Dis 1997;175(suppl 1):537-542.

Liver Transplantation and Surgery, Vol 4, No 2 (March), 1998: pp 185-187


Copyright © 1998 by the American Association for the Study of Liver Diseases