Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC.
Notarpaolo A, et al.
J Hepatol 2017; 66: 552-9

Background & Aims : The AFP model was shown to be superior to the Milan criteria for predicting hepatocellular carcinoma (HCC) recurrence after liver transplantation in a French population. Our aim was to test the AFP model in a non-French, post-hepatitic cirrhosis-based population of HCC candidates.

Methods: 574 patients transplanted for HCC in four Italian centers were studied. AFP score was assessed at the last evaluation before liver transplantation (LT). Probabilities of recurrence and survival were estimated by the log-rank test or competing risk analysis and compared according to the AFP model.

Results: 24.7% patients were beyond Milan criteria. HCC complicated hepatitis C virus (HCV) and hepatitis B virus (HBV) cirrhosis in 58.7% and 24% of the cases, respectively. Five-year probabilities of recurrence differed according to AFP score 62 vs. >2 in the whole population (13.2 ± 1.8% vs. 49.8 ± 8.7%, p <0.001, HR = 4.98), in patients within Milan criteria (12.8 ± 2.0% vs. 32.4 ± 12.1%, p = 0.009, HR = 3.51), beyond Milan criteria (14.9 ± 4.2% vs. 58.9 ± 11.5%, p <0.001, HR = 4.26), HCV patients (14.9 ± 2.5% vs. 67.6 ± 14.7%, p <0.001, HR = 6.56) and HBV patients (11.6 ± 3.4% vs. 34.3 ± 12.5%, p = 0.012, HR = 3.49). By net reclassification improvement analysis AFP score significantly improved prediction of non-recurrence compared to Milan criteria. Overall five-year survival rates according to AFP score 62 or >2 were 71.7 ± 2.2% vs. 42.2 ± 8.3% (p <0.001, HR = 2.14).

Conclusions: The AFP model identifies HCC candidates at low risk of recurrence, otherwise excluded by Milan criteria in a population with a predominance of post-hepatitic-related HCC. The AFP score can be proposed for selection of HCC candidates in programs with a high proportion of viral/HCV-related cirrhosis.

Expert's Commentary

Cumulative experience s over the last two decades have shown that M ilan criteria can be to o restrictive , excluding select ed subgroups of HCC who may benefit from LT . This has led to the development of numerous HCC expanded criteria worldwide. However , LT for HCC could only be justified when results are comparable to those of patients with non-malignant ind ications. According with the study by Notarpaolo, either reduction of recurrence or increase in survival can be achieved in patients with advanced HCCs if AFP level s at listing time point are predictively used according to the AFP model. The study demonstrates that it is possible to enlarge the basin of transplant candidates. Although the study offers a cross country and etiology validation of the AFP model, a personalized medicine approach - based on the i dentification of new genetic variants and therapeutic targets - may better refine the target population of advanced HCC LT candidates.

Alessandra Mangia, San Giovanni Rotondo, Italy