High Hepatitis B Viral Load Predicts Recurrence of Small Hepatocellular Carcinoma after Curative Resection

A retrospective cohort study was conducted to identify risk factors for recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. A total of 317 patients who had received curative resection of pathologically proven small HCC (≤3 cm in diameter) were analyzed to ascertain the factors affecting recurrence. The median follow-up period was 33.7 months. Cumulative recurrence rates at 1, 3, and 5 years after resection were 23.5%, 49.5%, and 65.5%, respectively. Male sex, alpha-fetoprotein (AFP) ≥400 ng/mL, HBV DNA level ≥4 log₁₀ copies/mL, prolonged prothrombin time, tumor size ≥2 cm, microvascular invasion, absence of capsular formation, moderate/poor tumor differentiation, and absence of postoperative interferon-alpha (IFN-α) treatment were associated with increased cumulative risk of HCC recurrence. By multivariate analysis, HBV DNA level ≥4 log₁₀ copies/mL (P < 0.001, hazard ratio (HR) 2.110), AFP ≥400 ng/mL (P = 0.011, HR 1.574), microvascular invasion (P < 0.001, HR 1.767), and postoperative IFN-α treatment (P = 0.022, HR 0.562) remained to be independently associated with HCC recurrence. Those contributing to late recurrence (>2 years) were older age and HBV DNA level ≥4 log₁₀ copies/mL. Patients with persistent HBV DNA level ≥4 log₁₀ copies/mL at resection and follow-up had the highest recurrence risk (P < 0.001, HR 4.129). HBV DNA level ≥4 log₁₀ copies/mL at the time of resection was the most important risk factor for recurrence. Postoperative IFN-α treatment significantly decreased the recurrence risk after resection.