Vaccination against Hepatitis B in Patients with Chronic Liver Disease Awaiting Liver Transplantation JOHN C. HORLANDER, SR, MD; NANCY BOYLE, RN; RAJESH MAN AM, MD; MELINDA SCHENK, RN; SCOTT HERRING, RN; PAUL Y. KWO, MD; LAWRENCE LUMENG, MD; NAGA CHALASANI, MD ABSTRACT: Background: Most transplant centers in the United States immunize patients awaiting liver transplantation against hepatitis B to prevent acquisi- tion of hepatitis B through transplantation (de novo hepatitis B). A recent study showed that only 16% of patients with cirrhosis awaiting liver transplantation responded to single-dose recombinant vaccine. Meth- ods: We studied the immunogenicity of double-dose recombinant vaccine in patients with cirrhosis await- ing liver transplantation. Results: Over a 4-year period (January 1994 to December 1997), 140 patients with cirrhosis without past or current hepatitis B infection were given double-dose recombinant vaccine (40 /Lg of Engerix B; SmithKline Beecham, Philadelphia, PA) at 0, 1 to 2, and 2 to 4 months. Hepatitis B surface antibody (HBsAb) was measured 1 to 3 months after completing vaccination. The response rate was 37%. H epatitis B virus (HBV) infection is an impor- tant cause of acute and chronic hepatitis as well as hepatocellular carcinoma. It has been es- timated that 300,000 HBV infections occur each year in the United States.1 Patients undergoing liver transplantation are considered at risk for acquiring HBV infection through liver transplan- tation (de novo HBV hepatitis B).2-5 The potential sources of de novo hepatitis B after liver trans- plantation include transfused blood products, oc- cult donor organ infection (donors who were hep- atitis B surface antigen-negative [HBsAg( -)] but hepatitis B core antibody-positive [HBcAb( +)]), and cryptic HBV in the recipient. 2 - 12 Most trans- From the Division of Gastroenterology and Hepatology, Depart· ment of Medicine, Indiana University School of Medicine, India· napolis, Indiana. Submitted October 19, 1998; accepted in revised form April 7, 1999. Correspondence: Naga Chalasani, M.D., Indiana University School of Medicine, WD OPW2005, 1001 W 10th street, Indianap· olis, IN 46202 (E.mail: nchalasa®iupui.edu). 304 However, HBsAb titers became undetectable in 35% of the responders during the post-transplant follow-up period. One hundred and thirty-seven patients under- went 144 liver transplantation procedures during the study period, and 3 patients developed de novo hep- atitis B (2.2%). Livers transplanted from hepatitis B core antibody (HBcAb)-positive donors was the source of de novo hepatitis B in all cases. Two of the 3 patients who developed de novo hepatitis B were immunized before transplantation and one of them was a responder. Conclusion: Although the re- sponse rate to double-dose recombinant vaccines is higher than the previously reported response to sin- gle-dose vaccine, it still is less than optimal. KEY INDEXING TERMS: Hepatitis B; Recombinant vac- cine; Orthotopic liver transplantation [Am J Med Sci 1999;318(5):304-7.] plant centers in the United States routinely vac- cinate patients awaiting liver transplantation against HBV to prevent de novo hepatitis B. Al- though healthy adults respond very well (>90%), patients with cirrhosis respond quite poorly to hepatitis B vaccines. Reported response rates of plasma-derived hepatitis B vaccines (no longer available in the US) in patients with cirrhosis and chronic liver disease have ranged from 13 to 54%.1 3 • 14 A recent study showed that response to single-dose recombinant vaccine in patients with cirrhosis awaiting liver transplantation was only 16%.1 6 Given such a poor response, authors of that study as well as an accompanying editorial sug- gested to explore alternative strategies to enhance the immunogenicity of these vaccines. 16 ,17 Pa- tients with renal failure who are on hemodialysis respond poorly to single-dose hepatitis B vaccines and are routinely administered double-dose vac- cines to achieve higher response rates. 2 In this report, we analyzed the immunogenicity of double- dose recombinant hepatitis B vaccine in a large cohort of patients with cirrhosis awaiting liver November 1999 Volume 318 Number 5