Ben-Ari Ziv, Weiss-Schmilovitz Hemda, Sulkes Jaqueline, Brown Marius, Bar-Nathan Nathan, Shaharabani Ezra, Yussim Alexander, Shapira Zaki, Tur-Kaspa Ran, Mor Eytan
Liver Institute and Department of Medicine D, Rabin Medical Center, Petah Tikva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Clin Transplant. 2004 Apr;18(2):130-6. doi: 10.1046/j.1399-0012.2003.00135.x.
Early cholestasis is not uncommon after liver transplantation and usually signifies graft dysfunction. The aim of this study was to determine if serum synthetic and cholestatic parameters measured at various time points after transplantation can predict early patient outcome, and graft function.
The charts of 92 patients who underwent 95 liver transplantations at Rabin Medical Center between 1991 and 2000 were reviewed. Findings on liver function tests and levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) on days 2, 10, 30, and 90 after transplantation were measured in order to predict early (6 months) patient outcome (mortality and sepsis) and initial poor functioning graft. Pearson correlation, chi(2) test, and Student's t-test were performed for univariate analysis, and logistic regression for multivariate analysis.
Univariate analysis. Serum bilirubin >/=10 mg/dL and international normalized ratio (INR) >1.6 on days 10, 30, and 90, and high serum ALP and low albumin levels on days 30 and 90 were risk factors for 6-month mortality; serum bilirubin >/=10 mg/dL on days 10, 30, and 90, high serum ALP, high GGT, and low serum albumin, on days 30 and 90, and INR >/=1.6 on day 10 were risk factors for sepsis; high serum alanine aminotransferase, INR >1.6, and bilirubin >/=10 mg/dL on days 2 and 10 were risk factors for poor graft function. The 6-month mortality rate was significantly higher in patients with serum bilirubin >/=10 mg/dL on day 10 than in patients with values of <10 mg/dL (29.4% vs. 4.0%, p = 0.004). Patients who had sepsis had high mean serum ALP levels on day 30 than patients who did not (364.5 +/- 229.9 U/L vs. 70.8 +/- 125.6 U/L, p = 0.005). Multivariate analysis. Significant predictors of 6-month mortality were serum bilirubin >/=10 mg/dL [odds ratio (OR) 9.05, 95% confidence intervals (CI) 1.6-49.6] and INR >1.6 (OR 9.11, CI 1.5-54.8) on day 10; significant predictors were high serum ALP level on day 30 (OR 1.005, 1.001-1.01) and high GGT level on day 90 (OR 1.005, CI 1.001-1.01). None of the variables were able to predict initial poor graft functioning.
Several serum cholestasis markers may serve as predictors of early outcome of liver transplantation. The strongest correlation was found between serum bilirubin >/=10 mg/dL on day 10 and early death, sepsis, and poor graft function. Early intervention in patients found to be at high risk may ameliorate the high morbidity and mortality associated with early cholestasis.
肝移植后早期胆汁淤积并不少见,通常意味着移植物功能障碍。本研究的目的是确定移植后不同时间点测量的血清合成和胆汁淤积参数是否能够预测患者早期预后以及移植物功能。
回顾了1991年至2000年间在拉宾医疗中心接受95例肝移植的92例患者的病历。测量移植后第2天、第10天、第30天和第90天的肝功能检查结果以及血清胆红素、碱性磷酸酶(ALP)和γ-谷氨酰转肽酶(GGT)水平,以预测患者早期(6个月)预后(死亡率和脓毒症)以及初始移植物功能不良。进行Pearson相关性分析、卡方检验和Student t检验用于单因素分析,并进行逻辑回归用于多因素分析。
单因素分析。移植后第10天、第30天和第90天血清胆红素≥10mg/dL以及国际标准化比值(INR)>1.6,以及第30天和第90天高血清ALP和低白蛋白水平是6个月死亡率的危险因素;移植后第10天、第30天和第90天血清胆红素≥10mg/dL,第30天和第90天高血清ALP、高GGT和低血清白蛋白,以及第10天INR≥1.6是脓毒症的危险因素;移植后第2天和第10天高血清丙氨酸氨基转移酶、INR>1.6和胆红素≥10mg/dL是移植物功能不良的危险因素。第10天血清胆红素≥10mg/dL的患者6个月死亡率显著高于胆红素<10mg/dL的患者(29.4%对4.0%,p = 0.004)。发生脓毒症的患者第30天的平均血清ALP水平高于未发生脓毒症的患者(364.5±229.9 U/L对70.8±125.6 U/L,p = 0.005)。多因素分析。6个月死亡率的显著预测因素是移植后第10天血清胆红素≥10mg/dL[比值比(OR)9.05,95%置信区间(CI)1.6 - 49.6]和INR>1.6(OR 9.11,CI 1.5 - 54.8);显著预测因素是移植后第30天高血清ALP水平(OR 1.005,1.001 - 1.01)和第90天高GGT水平(OR 1.005,CI 1.001 - 1.01)。没有变量能够预测初始移植物功能不良。
几种血清胆汁淤积标志物可作为肝移植早期预后的预测指标。发现移植后第10天血清胆红素≥10mg/dL与早期死亡、脓毒症和移植物功能不良之间的相关性最强。对发现高危的患者进行早期干预可能改善与早期胆汁淤积相关的高发病率和死亡率。