国家在肝移植前对肝细胞癌降期的经验：肿瘤负担、甲胎蛋白和等待时间的影响。
National Experience on Down-Staging of Hepatocellular Carcinoma Before Liver Transplant: Influence of Tumor Burden, Alpha-Fetoprotein, and Wait Time.
机构信息
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA.
Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA.
出版信息
Hepatology. 2020 Mar;71(3):943-954. doi: 10.1002/hep.30879. Epub 2019 Oct 15.
BACKGROUND AND AIMS
United Network for Organ Sharing (UNOS) recently implemented a national policy granting priority listing for liver transplantation (LT) in patients who achieved down-staging of hepatocellular carcinoma (HCC) to Milan criteria. We aimed to evaluate the national experience on down-staging by comparing two down-staging groups with (1) tumor burden meeting UNOS down-staging (UNOS-DS) inclusion criteria and (2) "all-comers" (AC-DS) with initial tumor burden beyond UNOS-DS criteria versus patients always within Milan.
APPROACH AND RESULTS
This is a retrospective analysis of the UNOS database of 3,819 patients who underwent LT from 2012 to 2015, classified as always within Milan (n = 3,276), UNOS-DS (n = 422), and AC-DS (n = 121). Median time to LT was 12.8 months in long wait regions, 6.5 months in mid wait regions (MWR), and 2.6 months in short wait regions (SWR). On explant, vascular invasion was found in 23.7% of AC-DS versus 16.9% of UNOS-DS and 14.4% of Milan (P = 0.002). Kaplan-Meier 3-year post-LT survival was 83.2% for Milan, 79.1% for UNOS-DS (P = 0.17 vs. Milan), and 71.4% for AC-DS (P = 0.04 vs. Milan). Within down-staging groups, risk of post-LT death in multivariable analysis was increased in SWR or MWR (hazard ratio [HR], 3.1; P = 0.005) and with alpha-fetoprotein (AFP) ≥ 100 ng/mL at LT (HR, 2.4; P = 0.009). The 3-year HCC recurrence probability was 6.9% for Milan, 12.8% for UNOS-DS, and 16.7% for AC-DS (P < 0.001). In down-staging groups, AFP ≥ 100 (HR, 2.6; P = 0.02) was the only independent predictor of HCC recurrence.
CONCLUSIONS
Our results validated UNOS-DS criteria based on comparable 3-year survival between UNOS-DS and Milan groups. Additional refinements based on AFP and wait time may further improve post-LT outcomes in down-staging groups, especially given that reported 3-year recurrence was higher than in those always within Milan criteria.
背景与目的
美国器官共享联合网络（UNOS）最近实施了一项国家政策，给予达到米兰标准的肝细胞癌（HCC）降期的患者肝移植（LT）优先名单。我们旨在通过比较两组降期患者（1）肿瘤负担符合 UNOS 降期（UNOS-DS）纳入标准，（2）“所有患者”（AC-DS）初始肿瘤负担超出 UNOS-DS 标准与始终符合米兰标准的患者，来评估全国范围内的降期经验。
方法和结果
这是对 2012 年至 2015 年接受 LT 的 3819 名患者的 UNOS 数据库进行的回顾性分析，这些患者分为始终符合米兰标准（n=3276）、UNOS-DS（n=422）和 AC-DS（n=121）。在长等待区，LT 的中位时间为 12.8 个月，中等待区（MWR）为 6.5 个月，短等待区（SWR）为 2.6 个月。在肝移植标本中，AC-DS 中血管侵犯的比例为 23.7%，而 UNOS-DS 为 16.9%，米兰标准为 14.4%（P=0.002）。米兰、UNOS-DS（P=0.17 与米兰相比）和 AC-DS（P=0.04 与米兰相比）的术后 3 年 LT 生存率分别为 83.2%、79.1%和 71.4%。在降期组中，多变量分析显示 SWR 或 MWR（风险比[HR]，3.1；P=0.005）和 LT 时 AFP≥100ng/ml（HR，2.4；P=0.009）增加了 LT 后死亡的风险。米兰标准 HCC 复发率为 6.9%，UNOS-DS 为 12.8%，AC-DS 为 16.7%（P<0.001）。在降期组中，AFP≥100（HR，2.6；P=0.02）是 HCC 复发的唯一独立预测因素。
结论
我们的结果验证了基于 UNOS-DS 组与米兰组 3 年生存率相当的 UNOS-DS 标准。基于 AFP 和等待时间的进一步细化可能会进一步改善降期组的 LT 后结局，特别是因为报告的 3 年复发率高于始终符合米兰标准的患者。
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