Determination of Hepatitis B Immunoglobulin Infusion Interval Using Pharmacokinetic Half-life Simulation for Posttransplant Hepatitis B Prophylaxis
10.3346/jkms.2019.34.e251
- Author:
Shin HWANG
1
;
Gi Won SONG
;
Young Kyu CHUNG
;
Chul Soo AHN
;
Ki Hun KIM
;
Deok Bog MOON
;
Tae Yong HA
;
Dong Hwan JUNG
;
Gil Chun PARK
;
Young In YOON
;
Hwui Dong CHO
;
Jae Hyun KWON
;
Sang Hyun KANG
;
I Ji JEONG
;
Jin Uk CHOI
;
Sung Gyu LEE
Author Information
1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. shwang@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
Hepatitis B Virus;
Recurrence;
Liver Transplantation;
Hepatitis B Immunoglobulin;
Antiviral Agent
- MeSH:
Cross-Sectional Studies;
DNA;
Half-Life;
Hepatitis B virus;
Hepatitis B;
Hepatitis;
Humans;
Immunoglobulins;
Liver Transplantation;
Methods;
Recurrence
- From:Journal of Korean Medical Science
2019;34(38):e251-
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL). METHODS: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients. RESULTS: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant 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 a 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. CONCLUSION: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration.
