Meyers B R, Papanicolaou G A, Sheiner P, Emre S, Miller C
The Mount Sinai Medical Center, Division of Infectious Diseases and Transplantation, New York, New York 10029-6574, USA.
Transplantation. 2000 Jan 15;69(1):64-9. doi: 10.1097/00007890-200001150-00013.
Because increased hepatotoxicity was observed with first line antituberculous agents using four drug standard induction therapy in orthotopic liver transplant patients, we evaluated the efficacy and adverse effects of a novel continuation regimen for the treatment of tuberculosis in orthotopic liver transplant patients at a University Hospital in New York City.
The hospital records of all patients who were referred to Mount Sinai Hospital (n=924) and who underwent orthotopic liver transplant between September 1988 and May 1998 were reviewed. Data were collected from patient records. Nine orthotopic liver transplant patients (0.97%) developed tuberculosis over a 9.5-year period. A total of seven of nine (78%) patients had disseminated tuberculosis including two patients with meningitis. All mycobacterial isolates were sensitive to isoniazid, rifampin, pyrazinamide, and ethambutol. Standard induction therapy with three or four drugs was given for 2 months (mean). Hepatotoxicity related to the standard induction regimen developed in five of six (83.3%) patients. Liver biopsy during induction therapy revealed drug induced hepatitis in five of six (88%) patients and rejection in three of six (50%) patients. Continuation regimens consisted mainly of ethambutol and ofloxacin; mean length of therapy 9 months.
Overall mortality was 33.3% (three of nine patients) over a 4.5-year follow-up period. Tuberculosis associated mortality was 22.2%. One patient died before therapy, another died with concomitant bacterial sepsis during induction therapy. Six of seven patients are alive and disease free. One patient died of recurrent hepatitis C and graft failure without evidence of tuberculous infection at death. Another patient retransplanted for chronic rejection, remains disease free at 1 year. The mean follow-up for six patients that completed treatment was 3.75 years (2.5-5.3 years). Six patients are free of tuberculosis.
Our experience reveals that orthotopic liver transplant patients have poor tolerance for conventional therapy due to inherent toxicity of these agents and their concomitant bouts of organ rejection. Our nonconventional therapy yielded remarkably good results in that six patients, all with disseminated disease, were well after mean 3.5 years of follow-up. Consideration should be given to this novel follow-up therapy in patients without cavitary pulmonary disease who develop hepatotoxicity during induction.
由于原位肝移植患者采用四联药物标准诱导疗法的一线抗结核药物出现肝毒性增加的情况，我们在纽约市一家大学医院评估了一种新型维持治疗方案治疗原位肝移植患者结核病的疗效和不良反应。
回顾了1988年9月至1998年5月期间转诊至西奈山医院（n = 924）并接受原位肝移植的所有患者的医院记录。从患者记录中收集数据。9.5年期间，9例原位肝移植患者（0.97%）发生了结核病。9例患者中有7例（78%）发生播散性结核病，其中2例患有脑膜炎。所有分枝杆菌分离株对异烟肼、利福平、吡嗪酰胺和乙胺丁醇敏感。给予三药或四药标准诱导治疗2个月（平均）。6例患者中有5例（83.3%）出现与标准诱导方案相关的肝毒性。诱导治疗期间的肝活检显示，6例患者中有5例（88%）为药物性肝炎，6例患者中有3例（50%）为排斥反应。维持治疗方案主要包括乙胺丁醇和氧氟沙星；平均治疗时长9个月。
在4.5年的随访期内，总体死亡率为33.3%（9例患者中有3例）。结核病相关死亡率为22.2%。1例患者在治疗前死亡，另1例在诱导治疗期间死于并发的细菌败血症。7例患者中有6例存活且无疾病。1例患者死于复发性丙型肝炎和移植失败，死亡时无结核感染证据。另1例患者因慢性排斥反应接受再次移植，1年后仍无疾病。完成治疗的6例患者的平均随访时间为3.75年（2.5 - 5.3年）。6例患者无结核病。
我们的经验表明，原位肝移植患者对传统疗法耐受性差，原因是这些药物的固有毒性及其伴随的器官排斥反应。我们的非传统疗法取得了显著良好的效果，6例均为播散性疾病的患者在平均3.5年的随访后情况良好。对于诱导治疗期间出现肝毒性且无空洞性肺部疾病的患者，应考虑这种新型后续治疗方法。
