What have we learned about primary liver transplantation under tacrolimus immunosuppression? Long-term follow-up of the first 1000 patients
What have we learned about primary liver transplantation under tacrolimus immunosuppression? Long-term follow-up of the first 1000 patients
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DOI：
10.1097/00000658-199909000-00016
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发表时间：
1999-09-01
影响因子：
9
通讯作者：
Fung, J
中科院分区：
文献类型：
--
作者：
Jain, A;Reyes, J;Fung, J
目的总结他克莫司在原位肝移植(OLT)患者中的长期疗效和安全性，并探讨影响其远期发病率和死亡率的因素。背景1989年，他克莫司(FK506，Prograf)被引入作为初次肝移植的主要免疫抑制剂；许多后续试验证实了他克莫司与降低OLT后急性排斥反应和激素耐药排斥反应的相关性。累积使用他克莫司的经验也确定了它的短期和中期毒性。方法从1992年8月至1992年12月，在的一个中心连续1000例患者在他克莫司免疫抑制的情况下接受了一期原位肝移植，直到1999年1月。患者按年龄进行分类。术后平均随访93.4+/-11个月。患者存活率、移植物存活率(有相应的死亡原因和再次移植)和排斥率(以及相应的免疫抑制剂量)被检测为疗效参数。高血压、肾功能、恶性肿瘤发生率、糖尿病发生率和其他毒性被检查为安全参数。结果患者实际6年总存活率为68.1%，移植物存活率为62.5%，不同年龄组的存活率差异有统计学意义。在移植后第一年，感染、疾病复发、新发恶性肿瘤和心血管事件是长期随访期间移植物丢失和死亡的主要原因。与急性或慢性排斥反应相关的移植物丢失是罕见的。超过2年的急性排斥反应的发生率约为每年3%，而且大多数是对激素敏感的。大约70%的患者在第一年以上接受他克莫司的单一治疗；在最近的随访中，74.2%的患者仅接受他克莫司治疗。在6.1%的幸存者中，终末期肾脏疾病发生在随访期，需要透析或肾移植。大约三分之一的患者出现高钾血症和高血压。胰岛素依赖型糖尿病(包括移植前有糖尿病的患者)在第1年的发生率为14%，到第7年下降到11%。82例患者发生了新发恶性肿瘤，41例患者在整个随访期内出现了淋巴增生性疾病。结论在他克莫司免疫抑制下，患者和移植物的长期存活率很高。儿童患者比成人有更好的长期结果，部分原因是原始疾病的有限复发，这是晚期移植物丢失的最常见原因(除了患者死亡，最常见的是晚期新发恶性肿瘤和心血管事件的结果)。晚期排斥反应导致的移植物丢失很少见。
ObjectiveTo summarize the long-term efficacy and safety of tacrolimus in orthotopic liver transplant (OLT) recipients, as well as to examine the factors that influence long-term morbidity and mortality rates.BackgroundTacrolimus (FK506, Prograf) was introduced as primary immunosuppression for primary liver transplantation in 1989; many subsquent trials have verified the association of tacrolimus with decreased rates of acute rejection and steroid-resistant rejection after OLT. Cumulative experience with tacrolimus has also defined its shori- and intermediate-term toxicity.MethodsOne thousand consecutive patients undergoing primary OLT at a single center from August 1989 to December 1992, under tacrolimus immunosuppression, were followed until January 1999. Patients were categorized by age. Mean follow-up was 93.4 +/- 11 months after OLT. Patient survival, graft survival (with corresponding causes of death and retransplantation), and rejection rates (and corresponding doses of immunosuppression) were examined as efficacy parameters. Hypertension, renal function, incidence of malignancies, incidence of diabetes, and other toxicities were examined as safety parameters. survival rare was 62.5%, with significant differencesResultsActual 6-year overall patient survival rate was 68.1% and graft survival rate was 62.5%, with significant differences in the patterns of survival among the different age groups. After the first post-OLT year, infection, recurrence of disease, de novo malignancies, and cardiovascular events were the main causes of graft loss and death during the long-term follow-up. Graft loss related to either acute or chronic rejection was rare. The rate of acute rejection beyond 2 years was approximately 3% per year, and most were steroid-responsive. Approximately 70% of the patients were receiving tacrolimus monotherapy beyond year 1; at the latest follow-up, 74.2% were maintained on tacrolimus alone. In 6.1% of the survivors, endstage renal disease developed during the follow-up period, requiring either dialysis or kidney transplantation. Hyperkalemia and hypertension was observed in approximately one third of the patients. Insulin-dependent diabetes mellitus (including patients who had diabetes before the transplant) was observed in 14% in year 1, dropping to 11% in year 7. In 82 patients, de novo malignancies developed; in 41 patients, lymphoproliferative disorders developed during the entire follow-up period.ConclusionsLong-term patient and graft survival rates are excellent under tacrolimus immunosuppression. Pediatric patients have a better long-term outcome than adults, in part because of the limited recurrence of the original disease, which was the most common cause of late graft loss (other than patient death, most commonly the result of late de novo malignancies and cardiovascular events). Graft loss from late rejection was rare.