Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
J Korean Med Sci. 2019 Oct 7;34(38):e251. doi: 10.3346/jkms.2019.34.e251.
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).
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.
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.
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.
在乙型肝炎病毒（HBV）相关受者进行肝移植（LT）后，预防 HBV 复发至关重要。本研究通过优化乙型肝炎免疫球蛋白（HBIG）的给药，应用模拟半衰期（SHL），建立了个体化 HBV 预防方案。
本研究包括五个部分：第 1 部分使用 20 例患者开发了 SHL 估计方法；第 2 部分和第 3 部分评估了 SHL 变异性并开发了模拟模型，将其应用于 100 例患者；第 4 部分在 114 例患者中验证了模拟模型，第 5 部分是 660 例患者中 HBIG 输注间隔现状的横断面研究。
第 1 部分中，输注 10000IU HBIG 诱导乙型肝炎表面抗体（抗-HBs）效价额外升高 5252.5±873.7IU/L，比实际测量低 4.4%。20.0±3.7 天的平均 SHL 比实际测量长 2.2%。第 2 部分中，SHL 的个体内和个体间变异系数的中位数分别为 13.5%和 18.5%。移植前 HBV DNA 载量和移植后抗病毒治疗均不影响 SHL。第 3 部分，开发了一种使用 SHL 确定 HBIG 输注间隔的模拟模型。第 4 部分，114 例患者均成功地接受了≥8 周的常规 HBIG 输注间隔治疗，其中 89.4%的患者将间隔延长至≥12 周，目标谷抗-HBs 效价≥200IU/L。第 5 部分，47.4%的患者HBIG 用量过多，目标谷浓度为 500IU/L。
与实际测量相比，仅使用临床可用参数进行 SHL 估计似乎具有可靠的准确性。我们认为 SHL 估计有助于建立个体化 HBV 预防方案，以优化 HBIG 给药。
