Early Versus Late Hepatocellular Carcinoma Recurrence after Transplantation: Predictive Factors, Patterns, and Long-Term Outcome

Background. Hepatocellular carcinoma (HCC) is currently the first indication of liver transplantation (LT) in Europe and Asia-Pacific region and the third in the United States. HCC recurrence is the main complication affecting short-and medium-Term outcomes after LT. Methods. A total of 433 consecutive adult recipients transplanted for HCC between 2000 and 2017 (mean age: 57.8 ± 8.5 y; 83.8% were males) with a mean follow-up of 74.6 ± 58.6 months were included. Patients had to meet Milan criteria and, since 2014, alpha-fetoprotein score to be listed. Patients with HCC recurrence were classified into early (≤2 y) and late recurrence (>2 y) and were retrospectively reviewed. Results. Patients who developed recurrence (75 patients, 17%) had more tumors outside Milan and University of California San Francisco criteria, high alpha-fetoprotein score, and microvascular invasion at pathology. Early recurrence developed in 46 patients (61.3%); the overall 5-and 10-year survival rates of these patients from time of LT were 6.7% and 0%, which were significantly lower than those with late recurrence 64.0% and 27.1%, respectively (P < 0.001). The median survival times from the diagnosis of HCC recurrence were 15 and 17 months, respectively, in the 2 groups (P < 0.001). Multivariable Cox regression analysis identified alcoholic cirrhosis as etiology of the underlying liver disease (hazard ratio [HR] = 3.074; P = 0.007), bilobar tumor at time of LT (HR = 2.001; P = 0.037), and a tumor size (>50 mm) in the explant (HR = 1.277; P = 0.045) as independent predictors of early recurrence. Conclusions. Improving the prediction of early HCC recurrence could optimize patient selection for LT, potential adjuvant therapy with new targeted drugs and hence, improve long-Term survival.