Survival outcomes of liver transplantation for hepatocellular carcinoma in patients with normal, high and very high preoperative alpha-fetoprotein levels

AIM: To investigate the impact of alpha-fetoprotein (AFP) on long-term recurrence rate and overall survival and we also aimed to define the level of AFP leading to a higher risk of disease recurrence and affecting patient survival. METHODS: Data of adult patients who received liver transplant (LT) for hepatocellular carcinoma (HCC) at our hospital from January 2000 to December 2013 were reviewed. Reviewed data included demographic characteristics, preoperative AFP level, operative details, follow-up details, and survival outcomes. Patients were mostly listed for LT based on Milan or UCSF criteria. For the purpose of this study, normal AFP level was defined as AFP value < 10 ng/mL, high AFP level was defined as AFP value ≥ 10 to < 400 ng/mL, and very high AFP level was defined as AFP ≥ 400 ng/mL. The patients were divided into these 3 groups accordingly. Survival rates were plotted as Kaplan-Meier curves and compared by log-rank analysis. Continuous variables were expressed as median (interquartile range). Categorical variables were compared by Spearman’s test. Discriminative analysis was used to define the lowest value of AFP that could affect the overall survival in study population. Statistical significance was defined by a P value of < 0.05. RESULTS: Totally 250 adult patients underwent LT for HCC in the study period. Eight-four of them received deceased-donor LT and 166 had living-donor LT. The patients were divided into 3 groups: Group A, AFP < 10 ng/mL (n = 83); Group B, AFP ≥ 10 to < 400 ng/mL (n = 131); Group C, AFP ≥ 400 ng/mL (n = 36). The commonest etiology was hepatitis-B-related cirrhosis. The Model for End-stage Liver Disease scores in these groups were similar (median, 13 vs 13 vs 12; P = 0.745). The time to operation in Group A was longer (median, 94 vs 31 vs 35 d; P = 0.001). The groups were similar in hospital mortality (P = 0.626) and postoperative complication (P = 0.702). Pathology of explants showed that the 3 groups had similar numbers of tumor nodules, but the tumors in Group C were larger (A: 2.5 cm, B: 3.0 cm, C: 4.0 cm; P = 0.003). Group C had a bigger proportion of patients who were beyond Milan criteria (P = 0.010). Poor differentiation and vascular permeation were also more common in this group (P = 0.017 and P = 0.003 respectively). It also had poorer 5-year survival (A: 85.5%, B: 82.4%, C: 66%; P = 0.029). The 5-year disease-free survival was 84.3% in Group A, 80.1% in Group B, and 61.1% in Group C. Receiver operating characteristic area under the curve for AFP in predicting tumor recurrence was 0.685. The selected cut-off value was 54 ng/mL for AFP (C-index 0.685; 95%CI: 0.592-0.779; sensitivity 0.595; specificity 0.687). On discriminative analysis, AFP value of 105 ng/mL was shown to affect the overall survival of the patients. CONCLUSION: HCC patients with a high preoperative AFP level had inferior survival after LT. AFP level of 54 ng/mL was associated with disease recurrence, and AFP level of 105 ng/mL was found to be the cut-off value for overall survival difference.