Department of General Surgery and Cleveland Clinic Lerner College of Medicine, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH.
Dumont-UCLA Transplant and Liver Cancer Center, Department of Surgery, Ronald Reagan UCLA Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, CA.
Hepatology. 2020 Feb;71(2):569-582. doi: 10.1002/hep.30838. Epub 2019 Aug 19.
Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.
肝移植（LT）治疗肝细胞癌（HCC）的预后预测仍然是一个挑战。尽管米兰标准（MC）推广了 LT 治疗 HCC 的实践并改善了预后，但随着候选人群和肿瘤学异质性的增加，其预测特征已经恶化。我们试图在国际队列中验证和重新校准先前开发的、术前计算的、连续的风险评分——与肝移植相关的 HCC 风险评分（HALTHCC）。2002 年至 2014 年，北美、欧洲和亚洲的 16 个中心共纳入了 4089 例患者（MC 内和外各占 25.2%）。在随机选择的队列（n=1021）中重新校准了使用 LT 前 AFP、终末期肝病模型钠评分和肿瘤负荷评分的连续风险评分，并在其余队列（n=3068）中进行了验证。这项研究表明，不同地点和年份存在显著的异质性，反映了过去十年的实践趋势。在肝移植标本中，血管侵犯（VI）和低分化成分（PDC）随 HALTHCC 评分的增加而增加。风险最低的患者（HALTHCC 0-5）的 VI 和 PDC 发生率低于风险最高的患者（HALTHCC>35）（VI：7.7%[1.2-14.2] vs. 70.6%[48.3-92.9]；PDC：4.6%[0.1%-9.8%] vs. 47.1%[22.6-71.5]；P<0.0001）。这种趋势在 MC 状态下是稳健的。这项国际研究用于调整 HALTHCC 评分的系数。在重新校准之前，HALTHCC 在总生存（OS）方面具有最大的判别能力（C 指数=0.61），优于所有先前报道的评分。在重新校准后，复发（C 指数=0.71）和 OS（C 指数=0.63）的预后效用均增加。结论：这项大型国际试验验证并完善了连续风险指标 HALTHCC 在全球范围内确定 HCC 患者 LT 前风险的作用。有必要进行前瞻性试验，将 HALTHCC 引入临床实践。
