Hameed Bilal, Mehta Neil, Sapisochin Gonzalo, Roberts John P, Yao Francis Y
Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA.
Liver Transpl. 2014 Aug;20(8):945-51. doi: 10.1002/lt.23904. Epub 2014 Jul 12.
Serum alpha-fetoprotein (AFP) has been increasingly recognized as a marker for a poor prognosis after liver transplantation (LT) for hepatocellular carcinoma (HCC). Many published reports, however, have included a large proportion of patients with HCC beyond the Milan criteria, and the effects of incorporating AFP as an exclusion criterion for LT remain unclear. We studied 211 consecutive patients undergoing LT for HCC within the Milan criteria according to imaging under the Model for End-Stage Liver Disease organ allocation system between June 2002 and January 2009. The majority (93.4%) had locoregional therapy before LT. The median follow-up was 4.5 years (minimum = 2 years). The Kaplan-Meier 1- and 5-year patient survival rates were 94.3% and 83.4%, respectively. In a univariate analysis, significant predictors of HCC recurrence included vascular invasion [hazard ratio (HR) = 10, 95% confidence interval (CI) = 3.9-26, P < 0.001], a pathological tumor stage beyond the University of California San Francisco criteria (HR = 4.1, 95% CI = 1.36-12.6, P = 0.01), an AFP level > 1000 ng/mL (HR = 4.5, 95% CI = 1.3-15.3, P = 0.02), and an AFP level > 500 ng/mL (HR = 3.1, 95% CI = 1.04-9.4, P = 0.04). In a multivariate analysis, vascular invasion was the only significant predictor of tumor recurrence (HR = 5.6, 95% CI = 1.9-19, P = 0.02). An AFP level > 1000 ng/mL was the strongest pretransplant variable predicting vascular invasion (odds ratio = 6.8, 95% CI = 1.6-19.1, P = 0.006). The 1- and 5-year rates of survival without recurrence were 90% and 52.7%, respectively, for patients with an AFP level > 1000 ng/mL and 95% and 80.3%, respectively, for patients with an AFP level ≤ 1000 ng/mL (P = 0.026). Applying an AFP level > 1000 ng/mL as a cutoff would have resulted in the exclusion of 4.7% of the patients fr m LT and a 20% reduction in HCC recurrence. In conclusion, an AFP level > 1000 ng/mL may be a surrogate for vascular invasion and may be used to predict posttransplant HCC recurrence. Incorporating an AFP level > 1000 ng/mL as an exclusion criterion for LT within the Milan criteria may further improve posttransplant outcomes.
血清甲胎蛋白（AFP）越来越被认为是肝细胞癌（HCC）肝移植（LT）后预后不良的一个标志物。然而，许多已发表的报告纳入了很大比例超出米兰标准的HCC患者，将AFP作为LT的排除标准的影响仍不明确。我们研究了2002年6月至2009年1月期间在终末期肝病模型器官分配系统下根据影像学符合米兰标准接受LT的211例连续性HCC患者。大多数（93.4%）患者在LT前接受了局部区域治疗。中位随访时间为4.5年（最短 = 2年）。Kaplan-Meier法计算的1年和5年患者生存率分别为94.3%和83.4%。单因素分析中，HCC复发的显著预测因素包括血管侵犯[风险比（HR）= 10，95%置信区间（CI）= 3.9 - 26，P < 0.001]、超出加利福尼亚大学旧金山分校标准的病理肿瘤分期（HR = 4.1，95%CI = 1.36 - 12.6，P = 0.01）、AFP水平> 1000 ng/mL（HR = 4.5，95%CI = 1.3 - 15.3，P = 0.02）以及AFP水平> 500 ng/mL（HR = 3.1，95%CI = 1.04 - 9.4，P = 0.04）。多因素分析中，血管侵犯是肿瘤复发的唯一显著预测因素（HR = 5.6，95%CI = 1.9 - 19，P = 0.02）。AFP水平> 1000 ng/mL是预测血管侵犯的最强移植前变量（优势比 = 6.8，95%CI = 1.6 - 19.1，P = 0.006）。AFP水平> 1000 ng/mL的患者无复发生存的1年和5年率分别为90%和52.7%，AFP水平≤1000 ng/mL的患者分别为95%和80.3%（P = 0.026）。将AFP水平> 1000 ng/mL作为临界值会导致4.7%的患者被排除在LT之外，HCC复发减少20%。总之，AFP水平> 1000 ng/mL可能是血管侵犯的替代指标，可用于预测移植后HCC复发。将AFP水平> 1000 ng/mL作为米兰标准内LT的排除标准可能会进一步改善移植后结局。
