We previously reported the use of adefovir (ADV) in preventing de novo hepatitis B virus (HBV) infections in recipients of hepatitis B core antibody–positive (HBcAb+) liver transplantation (LT). We further hypothesized that prophylaxis could be discontinued in recipients who develop an acquired immunity from post-LT vaccination. Reviewing our vaccination data with longer term follow-up, we found new cases of de novo HBV despite ADV. We now report our vaccination results and another 1.1 years of follow-up.
Our methodology is described in our initial report. We enrolled 16 recipients (mean age = 54 ± 11 years, median follow-up = 2.9 years) of HBcAb+ livers who received ADV monoprophylaxis after LT. A double-dose recombinant hepatitis B surface antigen (HBsAg) vaccine (Engerix-B, GlaxoSmithKline) was administered monthly for 3 months 12 to 18 months after LT. Recipients with hepatitis B surface antibody (HBsAb) levels > 500 mIU/mL after 6 months were given the option of ADV withdrawal.
Seventy-five percent (12/16) were vaccinated. Overall, 38% (6/16) developed HBsAb+: 3 patients had titers > 500 mIU/mL and were weaned off ADV (over periods of 4, 4, and 22 months), whereas another 3 patients had titers < 500 mIU/mL (range = 5-367 mIU/mL). None of the patients who developed HBsAb developed de novo HBV, regardless of their antibody titers. None of the recipients who were HBsAb− before LT developed durable HBsAb titers. Surprisingly, 4 of the 16 recipients (25%), all of whom were HBsAb−/HBcAb− before LT, became HBsAg+ 1.0 to 3.5 years after LT, whereas this happened to only 1 recipient in our initial report. For 2 recipients, serum HBV DNA remained undetectable (<40 IU/mL); the other 2 recipients had elevated HBV DNA levels (86 and 1.7 × 108 IU/mL). None had evidence of clinically active hepatitis. Recipients were successfully switched to entecavir or tenofovir with or without emtricitabine with complete suppression of HBV DNA. Numerically, the patients who developed de novo HBV were more likely to have their ADV dose adjusted or substituted for renal insufficiency [75% (3/4) versus 42% (5/12), P = 0.56].
It is unclear why ADV declined in efficacy over time. Dose adjustments for renal insufficiency (from daily administration to administration every 2-3 days), which occurred for 62% (10/16), may have led to inadequate drug levels and breakthrough. Only 1 recipient was nonadherent. However, because more potent agents are available, on the basis of our latest follow-up data, we would not recommend ADV for preventing de novo HBV. Additionally, post-LT HBV vaccination does not reliably induce acquired immunity; it remains to be seen whether the recipients of prophylaxis will continue to have durable HBsAb titers.
Matthew S. Chang, M.D.1
Sonja K. Olsen, M.D.2
Elsa M. Pichardo, M.D.2
Scott Heese, M.P.H.2
Jessica B. Stiles, B.S.N.2
James V. Guarrera, M.D.2
Jean C. Emond, M.D.2
Robert S. Brown Jr, M.D., M.P.H.2
1Division of Gastroenterology, Hepatology, and Endoscopy Brigham and Women's Hospital Boston, MA
2Center for Liver Disease and Transplantation NewYork-Presbyterian Hospital/Columbia University and Weill Cornell Medical College New York, NY