Mehta Neil, Heimbach Julie, Lee David, Dodge Jennifer L, Harnois Denise, Burns Justin, Sanchez William, Roberts John P, Yao Francis Y
1 Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA. 2 Division of Transplantation, Department of Surgery, Mayo Clinic, Rochester, MN. 3 Department of Transplantation, Mayo Clinic, Jacksonville, FL. 4 Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, CA. 5 Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN.
Transplantation. 2017 Sep;101(9):2071-2078. doi: 10.1097/TP.0000000000001752.
It has been postulated that short wait time before liver transplant (LT) for hepatocellular carcinoma (HCC) results in the inclusion of tumors with aggressive biology, but prolonged wait time could result in a shift to more aggressive tumor behavior. We therefore test the hypothesis that a wait time "sweet spot" exists with a lower risk for HCC recurrence compared with the other 2 extremes.
This multicenter study included 911 patients from 3 LT centers with short, medium, and long wait times (median of 4, 7, and 13 months, respectively) who received Model for End Stage Liver Disease exception listing for HCC from 2002 to 2012.
Wait time, defined as time from initial HCC diagnosis to LT, was less than 6 months in 32.4%, 6 to 18 months in 53.7%, and greater than 18 months in 13.9%. Waitlist dropout was observed in 18.4% at a median of 11.3 months. Probability of HCC recurrence at 1 and 5 years were 6.4% and 15.5% with wait time of less than 6 or greater than 18 months (n = 343) versus 4.5% and 9.8% with wait time of 6 to 18 months (n = 397), respectively (P = 0.049). When only pre-LT factors were considered, wait time of less than 6 or greater than 18 months (HR, 1.6; P = 0.043) and AFP greater than 400 at HCC diagnosis (HR, 3.0; P < 0.001) predicted HCC recurrence in multivariable analysis.
This large multicenter study provides evidence of an association between very short (<6 months) or very long (>18 months) wait times and an increased risk for HCC recurrence post-LT. The so-called sweet spot of 6 to 18 months should be the target to minimize HCC recurrence.
据推测,肝细胞癌(HCC)患者在肝移植(LT)前等待时间过短会导致具有侵袭性生物学行为的肿瘤被纳入移植范围,而等待时间过长则可能导致肿瘤行为转变为更具侵袭性。因此,我们检验了这样一个假设,即存在一个等待时间“最佳点”,与其他两个极端情况相比,HCC复发风险更低。
这项多中心研究纳入了来自3个LT中心的911例患者,这些患者的等待时间分别为短、中、长(中位数分别为4、7和13个月),他们在2002年至2012年期间因HCC获得了终末期肝病模型例外名单。
等待时间定义为从首次诊断HCC到LT的时间,小于6个月的占32.4%,6至18个月的占53.7%,大于18个月的占13.9%。在中位数为11.3个月时,观察到18.4%的患者从等待名单上退出。等待时间小于6个月或大于18个月(n = 343)的患者1年和5年HCC复发概率分别为6.4%和15.5%,而等待时间为6至18个月(n = 397)的患者分别为4.5%和9.8%(P = 0.049)。仅考虑LT前因素时,多变量分析显示等待时间小于6个月或大于18个月(HR,1.6;P = 0.043)以及HCC诊断时甲胎蛋白大于400(HR,3.0;P < 0.001)可预测HCC复发。
这项大型多中心研究提供了证据,表明极短(<6个月)或极长(>18个月)的等待时间与LT后HCC复发风险增加之间存在关联。6至18个月这个所谓的最佳点应成为将HCC复发降至最低的目标。