Role of accuracy measures in selecting hepatocellular carcinoma patients for liver transplantation
Authors: Frazão Laura P. , Pereira-Leal José B. , Duvoux Christophe , Cardoso Joana 
Published: January 2025

Structured Abstract

Importance

Multiple criteria are used worldwide to select hepatocellular carcinoma (HCC) patients with a low risk of recurrence for liver transplantation (LT). However, it remains unclear which criteria are best for the LT-involved stakeholders, particularly in accurately identifying patients at high risk of recurrence.

Objective

To identify the most accurate criteria for selecting HCC patients for LT.

Data Sources

In June 2023, a systematic literature search was conducted in PubMed and CENTRAL to identify studies including LT selection criteria of HCC patients.

Study Selection

The selected studies had LT selection criteria based solely on pre-LT variables. They included a minority of down-staged patients, over 80% of deceased donors, presented recurrence-free survival curves (or equivalent) with the number of patients at risk at different times, and had a follow-up period of over 3 years.

Data Extraction and Synthesis

Data was extracted from recurrence-free survival curves using a validated algorithm and subsequently used to calculate accuracy measures. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were applied.

Main Outcome(s) and Measures(s)

Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at 3- and 5-years post-LT.

Results

Of 815 records screened, only 17 met our study inclusion parameters, embodying 14 LT selection criteria. All LT criteria achieved an adjusted PPV (aPPV) over 80%, indicating the correct selection of at least 80% of low-risk HCC patients. However, the adjusted NPV (aNPV) was below 50% in most cases, indicating that these criteria cannot correctly identify patients with a true high risk of recurrence. This raises major ethical concerns regarding the models’ ability to exclude patients from LT. Since a perfect model is nonexistent, we created a ranking to account for the distinct concerns of all stakeholders in LT eligibility in the context of HCC.

Conclusions and Relevance

These results highlight the urgent need for new tools/models with improved NPV to select more patients amenable to LT who are currently excluded. Whether through refined existing criteria or newly developed criteria, emphasis should be placed on specificity and NPV as key performance indicators in the emerging era of transplant oncology.

Key points

Question:What are the best criteria to select patients with hepatocellular carcinoma for liver transplantation?

Findings:An objective ranking of existing criteria using accuracy measures considers the concerns of different stakeholders such as patients, physicians, payers, and organ allocation organisms. None of the analyzed criteria are ideal in satisfying all stakeholders in the selection of patients with hepatocellular carcinoma for liver transplantation. Criteria are even worse in accurately identifying patients who will not benefit from transplantation.

Meaning:There is a need to refine current criteria by focusing on specificity and negative predictive value as key performance indicators.