Research ArticleA novel waitlist dropout score for hepatocellular carcinoma – identifying a threshold that predicts worse post-transplant survival
Graphical abstract
Introduction
Following the implementation of the model for end-stage liver disease (MELD) system of organ allocation for hepatocellular carcinoma (HCC) in 2002, the proportion of liver transplants (LTs) performed in the USA for HCC has dramatically increased from <5% before 2002 to nearly 30%.[1], [2], [3] The rising incidence rates of HCC in the ageing hepatitis C population and in those with non-alcoholic fatty liver disease and metabolic syndrome are major contributing factors.[4], [5], [6], [7] Additionally, HCC screening in at-risk populations, recommended by all liver societies, increases the proportion diagnosed with early-stage HCC. As a result, HCC wait-list registrations in the USA rose by nearly 2000 within the 5 yr period from 2005–2009 to 2010–2014.8
As the transplant community is faced with the increasing demands of deceased donors for HCC, maximising LT survival benefit by improving patient selection (utility) must be carefully balanced against serving those with a higher risk for wait-list removal because of tumour progression (urgency).[9], [10], [11], [12] The lack of a reliable instrument built upon optimal LT timing for patients with HCC according to specific tumour characteristics represents 1 of the greatest challenges in organ allocation for HCC.11 Several systems have been proposed to give additional priority to patients with HCC with a greater risk for dropout, which typically include those with larger tumours and higher alpha-fetoprotein (AFP).[13], [14], [15], [16] This strategy, however, raises the concern of selecting those with less favourable tumour biology for LT, leading to a higher rate of post-LT HCC recurrence and worse survival.17,18
Another confounding factor is the wide regional variation in waiting time for LT across the USA.8,19 Regions with short-wait time offer the inherent advantage of rapid LT and a very low probability of wait-list dropout.8 Studies using the United Network for Organ Sharing (UNOS) database have also suggested worse post-LT survival and a greater risk of HCC recurrence with short-wait time,2,20 possibly because of inclusion of more aggressive tumours for LT without sufficient time to observe tumour behaviour.
In the present study, we analysed the risk of wait-list dropout among patients with HCC in long-wait regions (LWRs) to create a dropout risk score and to apply this score in mid-wait regions (MWRs) and short-wait regions (SWRs) to evaluate post-LT outcomes. Using this novel approach, we aimed to test the hypothesis that those with the highest dropout risk (determined in long-wait-time regions) have aggressive tumour biology that would also result in poor post-LT outcomes when transplanted in shorter-wait-time regions. Based on the same assumption, we also sought to identify a threshold in this dropout risk score beyond which LT should no longer be considered an acceptable immediate treatment option.
Section snippets
Study design and patient population
This was a retrospective cohort study of patients aged 18 yr and older listed for primary LT in the UNOS database (Standard Transplant Analysis and Research files released in March 2018) who received initial MELD exception for stage T2 HCC between January 2010 and December 2014. Patients were excluded from the study if they were listed for multi-organ transplant or received a living-donor LT. We also excluded patients who ever exceeded the Milan criteria before listing given that there was no
Patient characteristics
Baseline demographic and clinical characteristics of the 2092 patients with HCC comprising the LWR development cohort are summarised in Table 1 and compared with the 2 validation cohorts, which included 1735 patients listed in SWR and 2894 patients listed in MWR. Overall, the median age was 59 yr (IQR 55–63) and 76.6% were men. A significantly higher percentage of non-Caucasians were listed in LWR. Hepatitis C was the most common aetiology of liver disease. Hepatitis B and alcoholic liver
Discussion
HCC is a heterogeneous disease with highly variable patterns of progression after the initial diagnosis.25 This tumour heterogeneity is not accounted for under the traditional dogma of restricting LT for HCC solely on the basis of tumour size and number. Observing tumour behaviour following LRT while on the waiting list for LT has recently emerged as the main driver for improving candidate selection beyond the ‘1 size (and number) fits all’ approach.11,26 A crucial element in patient selection
Financial support
This work was supported by the Clinical & Translational Core of the University of California, San Francisco Liver Center (P30 DK026473).
Authors’ contributions
Concept and design: N.M., F.Y.Y.
Data acquisition, analysis, or interpretation: all authors
Drafting of paper: N.M., J.L.D., F.Y.Y.
Critical revision of paper for important intellectual content: all authors
Statistical analysis: N.M., J.L.D., F.Y.Y.
Supervision: J.P.R., F.Y.Y.
Data availability statement
The data that support the findings of this study are openly available in the UNOS database (Standard Transplant Analysis and Research files released March 2018).
Conflicts of interest
The authors declare no conflicts of interest that pertain to this work.
Please refer to the accompanying ICMJE disclosure forms for further details.
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2023, Clinical Gastroenterology and HepatologyCitation Excerpt :We found 3 factors associated with increased risk of dropout, including a higher listing MELD score, initial total tumor diameter, and initial AFP level >20 ng/mL. Previous studies similarly have found that HCC patients with more severe cirrhosis, based on MELD score or Child–Pugh class, have a high risk of waitlist dropout.16 Many patients with liver dysfunction have fewer LRT options and may receive less-aggressive treatments owing to the risk of hepatic decompensation after LRT and also are more likely to have liver-related death without LT. In addition, compared with AFP level ≤20 ng/mL, increasing AFP levels were found to be increasingly associated with a higher risk of dropout.