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Updated: Jan 13, 2026

A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Hepatocellular Carcinoma Transplant Criteria Show Poor Negative Predictive Value: A Systematic Review and
Laura P Frazão1, Margarida C Quaresma1, José B Pereira-Leal1
1Ophiomics-Precision Medicine, 1600-514 Lisboa, Portugal.
Abstract:
Background/Objectives: 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. This work aimed to identify the most accurate criteria for selecting HCC patients for LT. Methods: In June 2023, a systematic literature search was conducted in PubMed and CENTRAL to identify studies including LT selection criteria of HCC patients. Data was extracted from recurrence-free survival curves using a validated algorithm and subsequently used to calculate measures of diagnostic performance routinely used in clinical trials. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were applied. Results: Of 815 records screened, only 17 met our study inclusion parameters, embodying 14 LT selection criteria. All LT criteria achieved an adjusted positive predictive value (aPPV) over 80%, indicating the correct selection of at least 80% of low-risk HCC patients. However, the adjusted negative predictive value (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: These results highlight the urgent need for refined or newly developed criteria with improved specificity and NPV to select more patients amenable to LT who are currently excluded.
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