Rosen H R, Martin P, Goss J, Donovan J, Melinek J, Rudich S, Imagawa D K, Kinkhabwala M, Seu P, Busuttil R W, Shackleton C R
Department of Surgery, UCLA School of Medicine and Dumont-UCLA Transplant Center, Los Angeles, California 90095, USA.
Transplantation. 1998 Jan 15;65(1):68-72. doi: 10.1097/00007890-199801150-00013.
We retrospectively reviewed 213 consecutive patients who received their first liver allograft between January 1 and December 31, 1993, in order to study the impact of ischemia/preservation/reperfusion injury (IPRI) on patient and graft outcome.
The extent of IPRI was assessed by the peak value of aspartate aminotransferase (ASTmax) observed within the first 72 hr after transplant. For the purpose of univariate analysis, categorical classification of recipients was done based upon ASTmax as follows: group 1, ASTmax<600 U/L (n=46); group 2, ASTmax=600-2000 U/L (n=97); group 3, ASTmax>2000-5000 U/L (n=50), and group 4, ASTmax>5000 U/L (n=17). For multivariate analysis, stepwise Cox regression was performed with age, ASTmax, and United Network for Organ Sharing (UNOS) status as covariates.
Groups were comparable with respect to age, UNOS status at the time of transplantation, and diagnostic case mix. Median follow-up was 644 days. The overall incidence of primary graft nonfunction (PNF) was 7.6%. PNF incidence was significantly correlated with the severity of IPRI (0%, 4%, 10%, and 41% for groups 1 to 4, respectively, P < 0.0001), but this impact was confined to the respective rates of retransplantation as early patient survival was unaffected. The 1-year survival of patients whose initial grafts manifested extreme IPRI (group 4) was significantly inferior to recipients in the three other groups (77%, 71%, 73%, and 52% for groups 1 to 4, respectively, P=0.03). This increased mortality was confined to patients who never achieved discharge from their initial hospitalization, with no significant differences between groups being detected in the survival of those patients who were discharged (84%, 80%, 85%, and 81% for groups 1 to 4, respectively, P=NS). Although overall 1-year graft survival was strongly correlated with the extent of IPRI (77%, 67%, 62%, and 41% for groups 1 to 4, respectively, P=0.001), this correlation was abolished when survival of grafts not lost to PNF was examined at 1 and 2 years. Stepwise Cox regression analysis confirmed the independent association between ASTmax and patient and graft survival. The long-term quality of allograft function as well as the incidence of chronic rejection and biliary complications were unrelated to the extent of IPRI.
We conclude that: (1) patient survival is influenced by IPRI only when it is extreme (ASTmax>5000 U/L), provided parameters of graft function are used in conjunction with aminotransferase values to assess the need for prompt retransplantation; (2) short-term graft survival is proportional to the extent of IPRI, but grafts that are not lost to PNF have equivalent 1- and 2-year survival irrespective of the magnitude of IPRI; (3) 40% of grafts with extreme IPRI are lost to PNF, but the same proportion also provide long-term function; and (4) for surviving grafts, long-term biochemical function as well as the incidence of biliary complications and of chronic rejection are unrelated to the extent of IPRI.
我们回顾性分析了1993年1月1日至12月31日期间连续接受首例肝脏移植的213例患者，以研究缺血/保存/再灌注损伤（IPRI）对患者和移植物预后的影响。
通过移植后72小时内观察到的天冬氨酸转氨酶峰值（ASTmax）评估IPRI的程度。为进行单因素分析，根据ASTmax对受者进行分类如下：第1组，ASTmax<600 U/L（n = 46）；第2组，ASTmax = 600 - 2000 U/L（n = 97）；第3组，ASTmax>2000 - 5000 U/L（n = 50），第4组，ASTmax>5000 U/L（n = 17）。进行多因素分析时，以年龄、ASTmax和器官共享联合网络（UNOS）状态作为协变量进行逐步Cox回归分析。
各组在年龄、移植时UNOS状态和诊断病例组合方面具有可比性。中位随访时间为644天。原发性移植物无功能（PNF）的总体发生率为7.6%。PNF发生率与IPRI的严重程度显著相关（第1至4组分别为0%、4%、10%和41%，P < 0.0001），但这种影响仅限于再次移植的相应比率，因为早期患者生存率未受影响。初始移植物表现出极度IPRI（第4组）的患者1年生存率显著低于其他三组患者（第1至4组分别为77%、71%、73%和52%，P = 0.03）。这种死亡率的增加仅限于那些从未从首次住院中出院的患者，在出院患者的生存率方面，各组之间未检测到显著差异（第1至4组分别为84%、80%、85%和81%，P = 无显著性差异）。尽管总体1年移植物生存率与IPRI的程度密切相关（第1至4组分别为77%、67%、62%和41%，P = 0.001），但在1年和2年时检查未因PNF而丢失的移植物生存率时，这种相关性消失。逐步Cox回归分析证实了ASTmax与患者和移植物生存率之间的独立关联。同种异体移植物功能的长期质量以及慢性排斥反应和胆道并发症的发生率与IPRI的程度无关。
我们得出以下结论：（1）仅当IPRI极端严重（ASTmax>5000 U/L）时，患者生存率才会受到影响，前提是结合移植物功能参数与转氨酶值来评估及时再次移植的必要性；（2）短期移植物生存率与IPRI的程度成正比，但未因PNF而丢失的移植物无论IPRI的严重程度如何，其1年和2年生存率相当；（3）40%表现出极度IPRI的移植物因PNF而丢失，但相同比例的移植物也能提供长期功能；（4）对于存活的移植物，长期生化功能以及胆道并发症和慢性排斥反应的发生率与IPRI的程度无关。
