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The tertiary prevention of hepatocellular carcinoma in chronic hepatitis C patients. BACKGROUND AND AIM: Pegylated interferon-alpha plus ribavirin combination (PegIFN/RBV) therapy possesses positive effect in the secondary prevention of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. The current study aimed to assess its efficacy in the tertiary prevention and to validate the performance of the MHC class I polypeptide-related chain A (MICA) level in the prediction of hepatocellular carcinoma (HCC) recurrence. METHODS: A multi-center study enrolling 105 consecutive HCC patients post curative therapies were prospectively recruited. The primary outcome measurement was recurrence of HCC. RESULTS: The mean observational period was 52.7 months (range = 3.9-121.5 months). Fifty-six (53.3%) patients achieved sustained virological response (SVR). After completion of treatment, 43 (41.0%) patients developed HCC recurrence, and 24 (55.8%) of them had their recurrence within 6 months after completion of therapy. Thirty-three (76.7%) of the patients with HCC recurrence were of de novo pattern. Those responders tended to have a lower cumulative incidence of recurrence than those non-responders (43.2 vs 84.8/100 person-month, log-rank P = 0.13). Those non-responders with a high MICA level (>100 pg/mL) carried the lowest cancer-free survival than those non-responders with a low MICA level and those responders (P = 0.002). Cox regression hazard analysis showed high baseline MICA level (Odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.1-20.8, P = 0.04) and a low platelet count (<100 000/mm(3) ) (OR = 5.4, 95% CI = 1.1-27.0, P = 0.04) predicted HCC recurrence. CONCLUSIONS: PegIFN/RBV therapy carried a limited effect in the tertiary prevention of HCC. A high MICA level predicted HCC recurrence, particularly among those non-responders.