De novo hepatitis b prophylaxis with hepatitis B virus vaccine and hepatitis B immunoglobulin in pediatric recipients of core antibody–positive livers

Abstract

The use of hepatitis B core antibody-positive (HBcAb1) grafts for liver transplantation (LT) has the potential to safely expand the donor pool, as long as proper prophylaxis against de novo hepatitis B (DNHB) is employed. The aim of this study was to characterize the longterm outcome of pediatric LT recipients of HBcAb1 liver grafts under a prophylaxis regimen against DNHB using hepatitis B virus (HBV) vaccine and hepatitis B immunoglobulin (HBIG). From June 1996 to February 2013, 49 patients receiving pediatric LT at our center were from HBcAb1 donors. Forty-one patients who received DNHB prophylaxis according to our protocol were included in this analysis. Our DNHB prophylaxis protocol consists of HBV vaccine intramuscular injections given intermittently to maintain anti-hepatitis B surface antibody (HBsAb) titers above 100 IU/L. HBIG was also used during the first posttransplant year with a target anti-HBsAb titer level above 200 IU/L. There were 19 boys and 22 girls. Median age was 1.0 year (range, 4 months to 16 years). Median follow-up time was 66 months after transplant. Median annual number of HBV vaccine injections was 0.8 per year (range, 0-1.8 per year). Four patients did not require any HBV vaccine injections during follow-up. One patient with DNHB was encountered during the follow-up period (1/41, 2.4%). DNHB was diagnosed at 3.5 years after transplant, when hepatitis B surface antigen was positive upon routine follow-up serologic testing. Anti-HBsAb titer was 101.5 IU/L at the time. No grafts were lost because of DNHB-related events. Overall survival of the 41 recipients of HBcAb1 grafts who received DNHB prophylaxis was 92.3% at 10 years after transplant. In conclusion, longterm prophylaxis against DNHB with HBV vaccine in pediatric LT recipients of HBcAb1 grafts was safe and effective in terms of DNHB incidence as well as graft and patient survival. The use of hepatitis B core antibody-positive (HBcAb1) grafts for liver transplantation (LT) has the potential to expand the donor pool, especially in hepatitis B virus (HBV) endemic areas.1 Studies have found the use of HBcAb1 livers to be safe as long as proper prophylaxis against de novo hepatitis B (DNHB) is employed.2,3 Several different approaches for DNHB prophylaxis have been used in recipients of HBcAb1 livers according to preference and experience of each institution, including nucleos(t)ide analogues (NUCs) and hepatitis B immunoglobulin (HBIG) or a combination of both. 4 A recently published consensus guideline recommended the use of lamivudine for DNHB prophylaxis in this clinical setting.5 However, this consensus guideline could not set forth an optimal recommendation for the pediatric population, whereas adding that HBV Abbreviations: DNHB, de novo hepatitis B; HBcAb1, hepatitis B core antibody-positive; HBIG, hepatitis B immunoglobulin; HBsAb, hepatitis B surface antibody; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; LT, liver transplantation; NUC, nucleos(t)ide analogue; PELD, Pediatric End-Stage Liver Disease.Grants or...

INASL Guidelines on Management of Hepatitis B Virus Infection in Patients receiving Chemotherapy, Biologicals, Immunosupressants, or Corticosteroids

“…161 In view of high price of HBIG, a more cost effective strategy of sustaining high titers of anti-Hbs is booster doses of vaccination at around end of first year post transplant when the steroid is either in minimal dosage or stopped. 162 The vaccination doses were found to be 0.8 per year to keep the adequate levels of anti-HBs and the need for HBIG was brought down from 4 booster doses per year to 0.1 booster dose per year. 162 Even 3 booster doses post-transplant were enough to allow anti-HBs levels > 1000 IU in 78% of the children who received anti-HBc positive graft.…”

“…162 The vaccination doses were found to be 0.8 per year to keep the adequate levels of anti-HBs and the need for HBIG was brought down from 4 booster doses per year to 0.1 booster dose per year. 162 Even 3 booster doses post-transplant were enough to allow anti-HBs levels > 1000 IU in 78% of the children who received anti-HBc positive graft. 161 In a more recent pediatric study, preventive therapy was the only significant risk factor for preventing de novo hepatitis which was found in significantly more (P = 0.037) proportions of recipients with anti-HBc positive grafts (7/44) versus those with anti-HBc negative grafts (1/57).…”

Updated Hepatitis B Guidance: Implications for liver transplant patients

“…More recently, novel strategies including active immunization of recipients before and after liver transplantation with monitoring of HBsAb titers have been reported. This approach may offer a more cost‐effective strategy, eliminating the need for longterm NAs . However, this approach requires careful monitoring of vaccine response and may be most practical in the setting of living donor liver transplantation, where the vaccine may be administered before transplant in nonimmune recipients .…”

“…This approach may offer a more costeffective strategy, eliminating the need for longterm NAs. (51,52) However, this approach requires careful monitoring of vaccine response and may be most practical in the setting of living donor liver transplantation, where the vaccine may be administered before transplant in nonimmune recipients. (53) This vaccination strategy should be studied in future larger trials.…”

Vaccination against viral hepatitis b in pediatric liver transplant recipients

“…По данным ряда исследователей, титры сыво-роточных анти-HBs должны поддерживаться на уровнях более 100 МЕ/л [10,[26][27][28][29]. Для отдельных групп пациентов c высокими рисками развития HBV-инфекции рекомендованный целевой уровень антител может быть выше: 100-250 МЕ/л [30], 100-500 МЕ/л [31,32], тогда как в некоторых исследова-ниях считается достаточным уровень более 10 МЕ/л [12,23], более 20 МЕ/л [33].…”