B형간염 바이러스 부하와 B형간염 면역글로불린의 체내 반감기를 고려한 간이식 후 B형간염 예방 프로토콜의 최적화

Abstract

Backgrounds: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study was intended to establish individualized HBV prophylaxis protocol to optimize hepatitis B immunoglobulin (HBIG) administration with application of simulative half-life (SHL).

Methods: This study consisted of 5 parts: Part 1 was designed to develop SHL estimation method with 20 patients; Parts 2 and 3 were to assess variability of SHL and to develop a simulation model to apply SHL with 100 patients; Part 4 was to validate simulation model with 114 patients; and Part 5 was a cross-sectional study on current status of HBIG infusion intervals with 660 patients.

Results: In Part 1, add-on rise of anti-HBs titer from infusion of 10,000 IU HBIG and means SHL were 5252.5±873.7 IU/L and 20.0±3.7 days respectively, which was 4.4% lower and 2.2% longer than those from actual measurement. In Part 2, the median values of intra-and inter-individual coefficient of variation were 13.5% and 18.5%, respectively. Pre-transplant HBV DNA load and post-transplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥8 weeks and the interval was prolonged to ≥12 weeks in 89.4% with target trough anti-HBs titer ≥200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively at a target trough titer of 500 IU/L.

Conclusions: SHL estimation using clinically available parameters seems to be reliably accurate comparing with results from actual measurement. We believe that SHL estimation is helpful to establish personalized HBV prophylaxis protocol to optimize HBIG administration.