IMPACT OF SERUM ALPHA FETOPROTEIN LEVELS ON THE RISK OF HEPATOCELLULAR CARCINOMA RECURRENCE AFTER LIVER TRANSPLANTATION

Introduction: Despite restrictive criteria for the selection of liver transplant (LT) candidates for hepatocellular carcinoma (HCC), 20% of patients evolve with tumor recurrence (TR), being post-recurrence survival in two years less than 10%. Based on purely structural data, the Milan criteria (MC) are not able to predict the biological behavior of such tumors. Alpha fetoprotein (AFP) is a biomarker that has a prognostic impact on HCC. It is argued that high levels of AFP are related to a higher burden of disease and/or more aggressive histological subtypes. Objectives: To assess the association between AFP serum levels in patients with HCC who underwent LT, explants histopathological data and TR risk. Methods: A retrospective cohort study comprised 192 patients submitted to LT for HCC at a reference center, between 2000 and 2016, with outpatient follow-up after transplantation until 12/31/2018. Thirty-five obitum cases were excluded from the survival analysis in the first three months after LT, thus 153 patients were analysed. Results: The sample comprised mainly male patients (76%), with a median age of 62 years old. The main etiologies were HCV (52.6%), HBV (11.9%) and alcohol (16.6%). Bridging treatments were performed in 79% of patients, with median list time of 89 (IQR 35-140) days. AFP ranged from 0.7 to 34,000 ng/mL, median of 19.3 (IQR 6.8-142.4) ng/mL. Normal AFP were verified in 35% of cases, and other 35% presented AFP between 10-100 ng/mL, 18.7% between 100-1000 ng/mL and 10.4% greater than 1000 ng/mL. In the explant analysis, 29.8% of tumors were outside the MC and 44.6% presented with vascular invasion, with an association between AFP > 1000 ng/mL and vascular invasion (p = 0.04). There was no association between AFP and the MC, nor with histological grade. TR risk after LT was progressively higher according to the pre-LT AFP extract (AFP 100-1000 ng/mL: HR 3.59, CI 1.38-9.31; AFP > 1000 ng/mL: HR 4.97, CI 1.8-13.7). In the multivariate analysis, AFP levels > 100 ng/mL persisted as an independent risk factor for TR. The median survival after recurrence was 10.1 months. There was no association between AFP after TR with post-recurrence survival. Conclusion: Although 35% of HCC-transplanted patients had normal AFP in pre-LT, AFP > 100 ng/mL was associated with higher risk of post-LT TR. Post-LT AFP monitoring, on the other hand, should not be used as the only way to monitor TR, since 41.2% of the recurrences did not revealed marker elevation.