Active Immunization Against De Novo Hepatitis B Virus Infection in Pediatric Patients After Liver Transplantation

Abstract

D onor organ shortages occasionally mandate the use of hepatic allografts from antibody to hepatitis B core antigen (anti-HBc) (ϩ) donors. The transplantation of anti-HBc (ϩ) livers carries a 25% to 95% risk of transmitting hepatitis B virus (HBV) to recipients, 1-6 although some of these studies showed lower rates of HBV infection in recipients who are anti-HBc/ anti-HBs (antibody to hepatitis B surface antigen) positive. 2,3,5,6 Several reports have recommended that some forms of prophylaxis should be undertaken to prevent de novo hepatitis B infection in recipients who received a graft from anti-HBc (ϩ) donors. 1,7-9 Hepatitis B immunoglobulin (HBIG) and/or lamivudine have been used for prophylaxis, but their life-long administration presents problems, such as a mutant strain emergence, high cost, and several side effects. Thus, active immunization is a better strategy than HBIG or lamivudine, if it is effective. Reports issued to date on the active immunization of patients waiting for liver transplantation [10][11][12] and who have undergone liver transplantation have not been satisfactory. 13,14 A poor response rate with vaccination and rapid decline in serum hepatitis B surface antibody (HBsAb) titer have been reported. 14 Recently, good results have been reported for the active immunization of selected patients after liver transplantation. 15

Different effect of HBV vaccine after liver transplantation between chronic HBV carriers and non-HBV patients who received HBcAb-positive grafts

“…In contrast, in non-HBV patients whose donors were HBcAb positive, good responses were reported in pediatric patients ranging from 70 to 90% [30][31][32][33]. In adult cases, there is one report showing a 5/9 (55.6%) response rate which is also a relatively good response [28].…”

Current use of hepatitis B immune globulin for prevention of de novo hepatitis B in recipients receiving anti-HBc-positive livers

“…Furthermore, prophylactic protocols may vary even within a center based on donor and recipient HBV serologic status. Table 2 summarizes published prophylactic protocols involving HBIG use at different transplant programs [15,18,20,21,24,26,27,29,[33][34][35][36][37][38][39][40][41][42][43]. There are a number of important questions that remain to be answered regarding prevention of DNH in anti-HBc-positive donor LT. We will address the following four questions.…”

“…Both articles suggest HBIG 10,000 IU IV during anhepatic phase and then daily 9 7 days, followed by HBIG 10,000 IU IV monthly 9 6 months, then HBIG 1,000 IU IM every 2 weeks 9 18 months plus LAM 150 mg daily lifelong Loss [35] HBIG 10,000 IU IV during anhepatic phase plus LAM 150 mg daily lifelong* Manzarbeitia [21] HBIG 10,000 IU IV monthly 9 6 months to maintain anti-HBs [100 IU/L Roque-Afonso [20] HBIG 5,000 IU IV daily 9 7 days, followed by booster to maintain anti-HBs [100 IU/L Holt [36] HBIG 10,000 IU IV daily 9 7 days plus LAM 150 mg b.i.d. 9 2 years Chang [37] HBIG 100 IU/Kg IV intraoperatively and then daily 9 3 days, followed by booster to maintain anti-HBs [20 IU/L plus vaccination based on anti-HBs titer Fabrega [38] HBIG 10,000 IU IV during anhepatic phase and then daily 9 7 days plus LAM 100 mg daily ¥ Nery [29] HBIG 10,000 IU IV intraoperatively and then daily 9 7 days, weekly 9 1 month, and monthly 9 6 months and/or LAM 150 mg daily lifelong } Lee [15] HBIG (100 IU/Kg for children and 10,000 IU for adults) IV daily 9 7 days, followed by booster to maintain antiHBs [ 200 IU/L Suehiro [39] HBIG 10,000 IU IV during anhepatic phase and then 2,000 IU IV daily 9 7 days, followed by 2,000 IU IV every 2 months to maintain anti-HBs [ 100 IU/L plus LAM 100 mg daily Donataccio [24] HBIG 10,000 IU IV during anhepatic phase and then daily that current available studies do not support prophylactic use of the combination therapy over LAM monotherapy in HBV DNA negative patients receiving anti-HBcpositive liver grafts. LAM monotherapy has the same efficacy as the combination therapy at far less cost [47,48].…”

Hepatitis B Vaccination and Anti–Hbc–Positive Livers in Children

“…All pediatricians reading the report by Chang et al 1 must have been as surprised as I was. Vaccination is such a standard care in pediatrics that usually we do not even think about talking about it.…”

“…In the article by Chang et al 1 the title was misleading because the main problem was not vaccination but the use of anti-HBc livers, and the protection conferred by vaccination. We do not have an answer because these children were not protected before, as they should have been.…”