Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy.
Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
Dig Dis Sci. 2019 Apr;64(4):1001-1007. doi: 10.1007/s10620-019-05538-1.
Hepatocellular carcinoma (HCC) as an indication to liver transplant (LT) started as palliative treatment, then moved to potentially curative anti-cancer therapy and more recently entered the era of competition with non-cancer indications, consequent to the need of the society to target equal distribution of the limited resource of donated organs among different indications. Nowadays HCC is a leading indication to LT, currently representing up to 50% of the indications in most transplant Centers. The risk of post-transplant death and the causes of mortality significantly vary along the post-transplant follow-up. Overall, the main causes of death after LT are multiple organ failure and cerebrovascular, cardiovascular, pulmonary, and renal complications. However, after the first post-LT year, mortality for technical complications, infections and general complications significantly decrease, while recurrence of primary liver diseases (particularly malignancies) increase, turning to be the main causes of death. In studies with time-to-event or survival outcomes, a competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. In the setting of LT for HCC, when the primary outcome of interest is death due to HCC recurrence, death due to causes different from this serves as a competing event because subjects who die from such different causes are no longer at risk of death due to HCC recurrence. The introduction of HCC-specific survival as a primary endpoint in studies assessing the outcomes of LT for HCC allows the identification of independent oncologic determinants of post-LT survival and their relative weight on patients' prognosis. In this view, a continuous model based on level of AFP, tumor size and tumor number that allows to determine the risk of death from HCC-related factors after liver transplantation ( www.hcc-olt-metroticket.org/ ) has been recently developed. Since the endpoint of HCC-specific survival is not influenced by the changes observed in short-term post-LT survival (thanks to advances in the clinical management) nor in long-term post-LT survival (thanks to the introduction of effective treatments achieving control of hepatitis B and C viruses), a model predicting HCC-specific survival will be an helpful prognostic tool in the context of the changing scenarios of LT for HCC.
肝细胞癌（HCC）作为肝移植（LT）的适应证，最初是作为姑息性治疗，然后发展为潜在的抗癌治疗，最近随着社会需要将有限的捐赠器官资源平等分配给不同的适应证，进入了与非癌症适应证竞争的时代。如今，HCC 是 LT 的主要适应证，目前在大多数移植中心占适应证的 50%左右。移植后死亡风险和死亡原因在移植后随访期间有显著差异。总的来说，LT 后死亡的主要原因是多器官衰竭以及脑血管、心血管、肺部和肾脏并发症。然而，在 LT 后第一年之后，技术并发症、感染和一般并发症导致的死亡率显著下降，而原发性肝病（特别是恶性肿瘤）的复发率增加，成为死亡的主要原因。在具有时间事件或生存结果的研究中，竞争风险是指一种事件，其发生排除了感兴趣的主要事件的发生。在 LT 治疗 HCC 的情况下，当主要结局是 HCC 复发导致的死亡时，由于其他原因导致的死亡则是一个竞争事件，因为死于这些不同原因的患者不再有 HCC 复发导致的死亡风险。将 HCC 特异性生存作为评估 LT 治疗 HCC 结果的主要终点引入研究中，可以确定 LT 后生存的独立肿瘤学决定因素及其对患者预后的相对权重。从这个角度来看，最近开发了一种基于 AFP 水平、肿瘤大小和肿瘤数量的连续模型，该模型可以确定移植后与 HCC 相关因素导致死亡的风险（www.hcc-olt-metroticket.org/）。由于 HCC 特异性生存的终点不受 LT 后短期生存变化（由于临床管理的进步）或 LT 后长期生存变化（由于有效治疗乙型和丙型肝炎病毒的引入）的影响，预测 HCC 特异性生存的模型将是 LT 治疗 HCC 不断变化的背景下一个有用的预后工具。
