*Purpose: Hepatocellular carcinoma (HCC) may be cured by liver transplantation (LT) in selected patients, though recurrence rates remain high. Patients who are reported as within Milan criteria by imaging are frequently found to be outside criteria on explant. This understaging of HCC worsens post-LT outcomes, however risk factors for understaging have not been elucidated. Furthermore, it is not known if there is regional or center-level variation in understaging.

*Methods: We conducted a retrospective analysis of adult patients transplanted for HCC in the United Network for Organ Sharing (UNOS) database between 2012 and 2016. Understaging was determined on the basis of comparing pre-LT imaging to explant findings. Kaplan-Meier methods and Cox regression were used to evaluate the impact of understaging on HCC recurrence and post-LT survival. Mixed-effects logistic regression was used to identify risk factors for understaging, and to study regional and center-level variation in adjusted analyses.

*Results: A total 5,424 patients were included in the cohort, of whom 22.6% (n=1,227) were understaged. Post-LT HCC recurrence and death were significantly associated with understaging (each p<0.001). In adjusted analyses (Table), independent predictors of understaging included age (OR 1.01, 95% CI 1.00 – 1.02), male sex (OR 1.56, 95% CI 1.32 – 1.85), downstaging (OR 4.81, 95% CI 3.15 – 7.36), and pre-LT AFP (p<0.001). There was also significant variation in understaging between UNOS regions and among transplant centers, ranging from 12.9% to 36.9% (Figure).

*Conclusions: We report novel risk factors for HCC understaging, which worsens post-LT outcomes. Significant center-level and regional variation in understaging highlights the need for standards that achieve greater uniformity in staging.

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