P42 Ki-67 and CK-19 as predictors of post-transplant HCC recurrence

<h3>Introduction</h3> Tumour recurrence after liver transplantation (LT) remains the dominant reason for reduced post-transplant survival in patients transplanted for hepatocellular carcinoma (HCC). Improved risk stratification would enable targetted post-LT surveillance and treatment. Several prognostic tools based on demographics, serum markers and tumour configuration, including the recently published R3-AFP model,¹ predict recurrence. However, none include molecular features of the explanted HCC, beyond AFP levels. Tumoral Ki67 and CK19 expression may predict aggressive tumour biology. We examined the prognostic significance of tumoral Ki67 and CK19 expression for HCC recurrence after LT. Secondly, we examined whether the addition of these biomarkers could refine the R3-AFP model. <h3>Methods</h3> We conducted a retrospective analysis of sequential patients undergoing LT at Addenbrooke’s Hospital, Cambridge, between January 2008 and December 2022. All patients had HCC on explant histopathology. Clinical and histopathological data was obtained retrospectively from a prospectively maintained database. Tumoral expression of Ki67 (MIB-1) and CK19 was performed retrospectively by immunohistochemistry and scored by a specialist hepatobiliary histopathologist. Cox regression analyses were used to assess factors predicting post-LT recurrence-free and overall survival. Statistical analyses were conducted using R. <h3>Results</h3> 277 patients (238 male (85.9%); median age 59.8 years (min-max: 23.1–73.6)) underwent LT during the study period. The cumulative incidence of recurrence at 5 years post-LT was 10.5% (95% CI: 7.0–14.8%). Significant univariate predictors of HCC recurrence included viral hepatitis (HR=2.54, p=0.026), elevated pre-transplant AFP (HR=1.17, p&lt;0.001), pre-transplant UKELD score (HR=2.54, p=0.026), number of lesions (HR=1.15, p&lt;0.001), size of largest lesion (HR=1.88, p&lt;0.001), tumour grade (p&lt;0.001) and microvascular invasion (p&lt;0.001). At univariate analysis, Ki67 (HR=1.38, p&lt;0.001) and CK19 expression were associated with HCC recurrence (HR=3.09, p&lt;0.016). After multivariate adjustment for other predictive factors neither Ki67 (HR=1.16, 0.98–1.38, p= 0.09) or CK19 (HR=1.66, 0.65–4.21, p= 0.29) expression were associated with HCC recurrence. Neither Ki67 (HR=1.13, 0.999 - 1.27, p=0.05) and CK19 (HR=1.68, 0.86 - 3.32, p=0.13) expression were associated with overall survival after transplant. In our cohort the R3-AFP score effectively stratified patient risk groups for recurrence, with a 5-year recurrence rate of 1% (95% CI: 0.1–4.8%) in very-low-risk patients and 32.6% (95% CI: 7.8–47.2%) in the very-high-risk group. Finally, Ki67 (p=0.077) and CK19 (p=0.338) expression could not predict post-LT HCC recurrence independent of R3-AFP risk score. <h3>Conclusion</h3> Tumoral Ki67 and CK19 expression do not confer additional prognostic utility for recurrence-free or overall survival after LT for HCC, beyond commonly-used clinicopathological variables or the R3-AFP score. <h3>Reference</h3> Costentin C, Piñero F, Degroote H, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Podestá LG, Bachellier P, Ettorre GM, Poniachik J, Muscari F, <i>et al</i>. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation.<i> JHEP Rep</i>. 2022;<b>4</b>(5):100445.