McGonigal Katrina H, Bajjoka Iman E, Abouljoud Marwan S
Creighton School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska.
Pharmacotherapy. 2013 Sep;33(9):e170-6. doi: 10.1002/phar.1306. Epub 2013 Jun 6.
In patients infected with chronic hepatitis B virus (HBV) that goes untreated, therapeutic options are limited once the disease decompensates, and orthotopic liver transplantation is often the only treatment available to save the patient's life. After liver transplantation, combined therapy with hepatitis B immune globulin (HBIG) and a nucleos(t)ide analog is the standard of practice for the prevention of HBV recurrence. Historically, nucleos(t)ide analogs such as lamivudine and adefovir have been used with low-dose HBIG for the prevention of HBV recurrence after liver transplantation. However, these analogs are ineffective when used alone due the emergence of resistance mutations. Newer nucleos(t)ide analogs such as tenofovir disoproxil fumarate have demonstrated higher resistance thresholds and effective viral suppression when paired with low-dose HBIG. In this case series, we evaluated the safety and efficacy of switching four patients from low-dose HBIG plus nucleos(t)ide analog therapy for the prevention of HBV recurrence to a combination tenofovir-emtricitabine regimen. At the end of follow-up, all patients remained hepatitis B surface antigen negative and had HBV DNA levels of less than 10 IU/ml. Additionally, no tenofovir-associated nephrotoxicity was observed among the four patients. Tenofovir-emtricitabine monotherapy in lieu of HBIG plus nucleos(t)ide analog therapy demonstrated prevention of HBV recurrence without tenofovir-associated nephrotoxicity after 9 months of follow-up in all four patients and up to 15 months in one patient.
在未经治疗的慢性乙型肝炎病毒（HBV）感染患者中，一旦疾病失代偿，治疗选择就很有限，原位肝移植往往是挽救患者生命的唯一可用治疗方法。肝移植后，联合使用乙型肝炎免疫球蛋白（HBIG）和核苷（酸）类似物是预防HBV复发的标准做法。从历史上看，拉米夫定和阿德福韦等核苷（酸）类似物一直与低剂量HBIG联合用于预防肝移植后的HBV复发。然而，由于耐药突变的出现，这些类似物单独使用时无效。富马酸替诺福韦二吡呋酯等新型核苷（酸）类似物与低剂量HBIG联合使用时，已显示出更高的耐药阈值和有效的病毒抑制作用。在本病例系列中，我们评估了4例患者从低剂量HBIG加核苷（酸）类似物治疗预防HBV复发转换为替诺福韦-恩曲他滨联合治疗方案的安全性和有效性。随访结束时，所有患者的乙型肝炎表面抗原均为阴性，HBV DNA水平低于10 IU/ml。此外，4例患者中均未观察到替诺福韦相关的肾毒性。在所有4例患者随访9个月以及1例患者随访长达15个月后，替诺福韦-恩曲他滨单药治疗替代HBIG加核苷（酸）类似物治疗显示可预防HBV复发，且无替诺福韦相关的肾毒性。
