Risk factors for exceeding the Milan criteria after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.

Radiofrequency ablation (RFA) is an effective and safe noninvasive treatment for hepatocellular carcinoma (HCC) and may be useful as a bridging therapy in liver transplantation. The prognosis after liver transplantation for patients within the Milan criteria is excellent. This study was aimed at identifying risk factors associated with exceeding the Milan criteria after initial locally curative RFA therapy. Among 554 primary HCC patients, 323 with early-stage HCC after RFA were analyzed (mean age = 66 years). Two hundred forty-eight patients had hepatitis C virus, 33 patients had hepatitis B virus, and 41 patients had neither hepatitis B nor hepatitis C; 256, 67, and 0 patients were classified as Child-Pugh A, B, and C, respectively. The rates of cumulative overall survival and recurrence exceeding the Milan criteria were analyzed with Kaplan-Meier analysis, and factors associated with overall survival were determined with Cox proportional hazards analysis. The cumulative overall survival rates at 1, 3, 5, and 10 years were 96.2%, 84.4%, 69.9%, and 40.6% respectively, without liver transplantation. The cumulative rates of recurrence exceeding the Milan criteria at 1, 3, and 5 years were 15.1%, 46.0%, and 61.1% respectively. An alpha-fetoprotein (AFP) level > 100 ng/mL and recurrence within 1 year after initial ablation were independently associated with earlier recurrence exceeding the Milan criteria and overall survival. The 3- and 5-year survival rates for patients with both risk factors were 33.5% and 22.6%, respectively, despite an early stage at initial ablation. In conclusion, a higher AFP level and HCC recurrence within 1 year of RFA are risk factors for exceeding the Milan criteria and for overall survival. Early liver transplantation or adjuvant therapy should be considered for patients with both risk factors.