Neil Mehta1, Jennifer L Dodge2, John P Roberts2, Francis Y Yao3. 1. Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Electronic address: neil.mehta@ucsf.edu. 2. Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA. 3. Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
Abstract
BACKGROUND & AIMS: It has been suggested that patients with hepatocellular carcinoma (HCC) at high risk of wait-list dropout would have done poorly after liver transplantation (LT) because of tumour aggressiveness. To test this hypothesis, we analysed risk of wait-list dropout among patients with HCC in long-wait regions (LWRs) to create a dropout risk score, and applied this score in short (SWRs) and mid-wait regions (MWRs) to evaluate post-LT outcomes. We sought to identify a threshold in dropout risk that predicts worse post-LT outcome. METHODS: Using the United Network for Organ Sharing database, including all patients with T2 HCC receiving priority listing from 2010 to 2014, a dropout risk score was created from a developmental cohort of 2,092 patients in LWRs, and tested in a validation cohort of 1,735 patients in SWRs and 2,894 patients in MWRs. RESULTS: On multivariable analysis, 1 tumour (3.1-5 cm) or 2-3 tumours, alpha-fetoprotein (AFP) >20 ng/ml, and increasing Child-Pugh and model for end-stage liver disease-sodium scores significantly predicted wait-list dropout. A dropout risk score using these 4 variables (C-statistic 0.74) was able to stratify 1-year cumulative incidence of dropout from 7.1% with a score ≤7 to 39.5% with a score >23. Patients with a dropout risk score >30 had 5-year post-LT survival of 60.1% vs. 71.8% for those with a score ≤30 (p = 0.004). There were no significant differences in post-LT survival below this threshold. CONCLUSIONS: This study provided evidence that patients with HCC with the highest dropout risk have aggressive tumour biology that would also result in poor post-LT outcomes when transplanted quickly. Below this threshold risk score of ≤30, priority status for organ allocation could be stratified based on the predicted risks of wait-list dropout without significant differences in post-LT survival. LAY SUMMARY: Prioritising patients with hepatocellular carcinoma for liver transplant based on risk of wait-list dropout has been considered but may lead to inferior post-transplant survival. In this study of nearly 7,000 patients, we created a threshold dropout risk score based on tumour and liver-related factors beyond which patients with hepatocellular carcinoma will likely have poor post-liver transplant outcomes (60% at 5 years). For patients below this risk score threshold, priority status could be stratified based on the predicted risk of wait-list dropout without compromising post-transplant survival.
BACKGROUND & AIMS: It has been suggested that patients with hepatocellular carcinoma (HCC) at high risk of wait-list dropout would have done poorly after liver transplantation (LT) because of tumour aggressiveness. To test this hypothesis, we analysed risk of wait-list dropout among patients with HCC in long-wait regions (LWRs) to create a dropout risk score, and applied this score in short (SWRs) and mid-wait regions (MWRs) to evaluate post-LT outcomes. We sought to identify a threshold in dropout risk that predicts worse post-LT outcome. METHODS: Using the United Network for Organ Sharing database, including all patients with T2 HCC receiving priority listing from 2010 to 2014, a dropout risk score was created from a developmental cohort of 2,092 patients in LWRs, and tested in a validation cohort of 1,735 patients in SWRs and 2,894 patients in MWRs. RESULTS: On multivariable analysis, 1 tumour (3.1-5 cm) or 2-3 tumours, alpha-fetoprotein (AFP) >20 ng/ml, and increasing Child-Pugh and model for end-stage liver disease-sodium scores significantly predicted wait-list dropout. A dropout risk score using these 4 variables (C-statistic 0.74) was able to stratify 1-year cumulative incidence of dropout from 7.1% with a score ≤7 to 39.5% with a score >23. Patients with a dropout risk score >30 had 5-year post-LT survival of 60.1% vs. 71.8% for those with a score ≤30 (p = 0.004). There were no significant differences in post-LT survival below this threshold. CONCLUSIONS: This study provided evidence that patients with HCC with the highest dropout risk have aggressive tumour biology that would also result in poor post-LT outcomes when transplanted quickly. Below this threshold risk score of ≤30, priority status for organ allocation could be stratified based on the predicted risks of wait-list dropout without significant differences in post-LT survival. LAY SUMMARY: Prioritising patients with hepatocellular carcinoma for liver transplant based on risk of wait-list dropout has been considered but may lead to inferior post-transplant survival. In this study of nearly 7,000 patients, we created a threshold dropout risk score based on tumour and liver-related factors beyond which patients with hepatocellular carcinoma will likely have poor post-liver transplant outcomes (60% at 5 years). For patients below this risk score threshold, priority status could be stratified based on the predicted risk of wait-list dropout without compromising post-transplant survival.
Authors: W R Kim; J R Lake; J M Smith; D P Schladt; M A Skeans; S M Noreen; A M Robinson; E Miller; J J Snyder; A K Israni; B L Kasiske Journal: Am J Transplant Date: 2019-02 Impact factor: 8.086
Authors: Neil Mehta; Jennifer L Dodge; Aparna Goel; John Paul Roberts; Ryutaro Hirose; Francis Y Yao Journal: Liver Transpl Date: 2013-12 Impact factor: 5.799
Authors: Zobair Younossi; Maria Stepanova; Janus P Ong; Ira M Jacobson; Elisabetta Bugianesi; Ajay Duseja; Yuichiro Eguchi; Vincent W Wong; Francesco Negro; Yusuf Yilmaz; Manuel Romero-Gomez; Jacob George; Aijaz Ahmed; Robert Wong; Issah Younossi; Mariam Ziayee; Arian Afendy Journal: Clin Gastroenterol Hepatol Date: 2018-06-14 Impact factor: 11.382
Authors: Quirino Lai; Alfonso W Avolio; Ivo Graziadei; Gerd Otto; Massimo Rossi; Giuseppe Tisone; Pierre Goffette; Wolfgang Vogel; Michael B Pitton; Jan Lerut Journal: Liver Transpl Date: 2013-10 Impact factor: 5.799
Authors: Sarah Bernards; Ryutaro Hirose; Francis Y Yao; Chengshi Jin; Jennifer L Dodge; Chiung-Yu Huang; Neil Mehta Journal: Liver Transpl Date: 2021-12-08 Impact factor: 5.799
Authors: Allison Kwong; Bilal Hameed; Shareef Syed; Ryan Ho; Hossein Mard; Sahar Arshad; Isaac Ho; Tashfeen Suleman; Francis Yao; Neil Mehta Journal: Cancer Med Date: 2022-01-14 Impact factor: 4.452