Pharmacokinetics of intramuscular and intravenous HBIG: Which implications for practice?

Abstract

A major achievement for patients transplanted for hepatitis B virus (HBV) associated end-stage liver disease is the successful prevention of reinfection with high dose of hepatitis B immunoglobulin (HBIG). The introduction of lamivudine in combination with HBIG reduces recurrence rates to less than 5% at 5 years. Currently, this combination is the accepted standard regimen in most transplantation units. However, a major drawback of this therapy is that high-dose intravenous (IV) HBIG is very expensive. Several strategies have been explored to reduce such costs. These include withdrawal of HBIG at some time after transplantation while continuing lamivudine, vaccination of patients prior to cessation of HBIG and substitution of high-dose IV HBIG by low-dose intramuscular (IM) HBIG. It has been demonstrated that crucial pharmacokinetic parameters, including anti-HBs antibodies through levels at time of HBIG re-administration, do not differ significantly after IV and IM administration in stable hepatitis B surface antigen (HBsAg) negative patients with at least 12 months follow-up after orthotopic liver transplantation, confirming the cost-effectiveness of IM HBIG administration. Recent studies suggest that, compared with combination of HBIG plus lamivudine prophylaxis, the combination of adefovir plus lamivudine prophylaxis provides equivalent protection against HBV reinfection with better tolerability at a significantly lower cost. Nonetheless, HBIG continue to be the cornerstone of HBV recurrence prevention.