Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection

Background/Aim: Time-dependent intrahepatic recurrence of hepatocellular carcinoma is frequent after different treatment modalities, including percutaneous ethanol injection. We attempted to prospectively analyze the possible risk factors for early intrahepatic recurrence of hepatocellular carcinoma after percutaneous ethanol injection. Methods: Sixty-five patients with 65 solitary hepatocellular carcinoma nodules less than or equal to 6 cm in diameter underwent initial treatment with percutaneous ethanol injection and were examined to ascertain the factors related to recurrence, local and distant, within the liver. A number of clinical and tumor parameters were analyzed. Results: Cumulative overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 15.6% and 45.1%, respectively, irrespective of clinical and tumor parameters. Overall recurrence rates 12 and 24 months after percutaneous ethanol injection were 40% and 67.5%, for tumor greater than or equal to 3 cm and 7.5% and 37.5%, for tumor <3 cm. Cumulative local recurrence rates at 12 and 24 months were 26.3% and 43.5%, respectively, for tumor greater than or equal to 3 cm and 11.7% and 18.2%, respectively, for tumor <3 cm. The log-rank test indicated that a tumor size of greater than or equal to 3 cm and the presence of capsule for a tumor of <3 cm in diameter were significant risk factors for intrahepatic recurrence. A pretreatment serum PIVKA-II level of greater than or equal to 0.02 AU/ml was the only clinical parameter associated with overall recurrence (p = 0.0041) and distant intrahepatic recurrence (p = 0.0307). Distant intrahepatic recurrence rates 12 and 24 months after percutaneous ethanol injection were 22.5% and 31.4%, respectively, for PIVKA-II levels of greater than or equal to 0.02 AU/ml and 8% and 17.8%, for PIVKA-II of <0.02 AU/ml. Cox's proportional hazard model identified that tumor size, tumor capsule and baseline serum PIVKA-II levels were independently related to intrahepatic recurrence. Conclusions: These data demonstrate that tumor size and peritumoral capsule,were associated with overall and local recurrence of hepatocellular carcinoma. Moreover, pretreatment serum levels of PIVKA-II can indicate the risk of early intrahepatic recurrence and may assist in patient selection and appropriate therapy.