Influence of hepatitis B virus DNA elevation on recurrence of hepatocellular carcinoma after surgical resection and the preventive role of antiviral therapy

초록

Aims Surgical resection is the treatment of choice for early stage hepatocellular carcinoma (HCC). Previous studies revealed that reactivation of hepatitis B virus is associated with the recurrence of hepatitis B virus (HBV) related HCC after surgical resection. We aimed to investigate the influence of HBV DNA elevation on HCC recurrence and the preventive role of antiviral therapy. Methods One hundred eleven patients who had BCLC stage 0 or A and received surgical resection as primary therapy were enrolled. HBV DNA elevation was defined as reactivation (increase >1log10 IU/ml or re-emergence of HBV DNA) in patients without preoperative antiviral therapy or virologic breakthrough in patients with preoperative antiviral therapy (n=62). Results Mean age was 54.1±9.4 years and male consisted 76.6% (n=85). All patients belonged in Child class A. BCLC 0 consisted 29.7% (n=33) and 30.6% (n=34) had Hepatitis B envelope antigen positivity and 42.3% (n= 47) had HBV DNA level ≥ 2000 IU/mL at the time of surgery. Overall 1 year, 3 year, 5 year recurrence was 17.3%, 36.4%, 40%. In multivariate analysis for risk factors of recurrence, multiple tumor, HBV DNA elevation, ALT ≥ 30 IU/L, were independently associated with HCC recurrence. In subgroup analysis, patients with preoperative antiviral therapy showed similar HCC recurrence rate with patients who start antiviral therapy after resection and significantly higher recurrence rate than patients with no antivirals during follow up. In multivariate analysis for risk factors of HBV DNA elevation, Age < 50 years, no preoperative antiviral therapy, HBV DNA ≥ 2000 remained as risk factors. To rule out the antiviral effect, we investigated risk factors for HCC recurrence in each group with or without preoperative antiviral therapy. In patients with preoperative antiviral therapy, multiple tumor was the only risk factor for HCC recurrence. In patients without preoperative antiviral therapy, male sex and HBV DNA elevation were independent risk factors for HCC recurrence. Risk factors for HBV DNA elevation were further analyzed in patients without preoperative antiviral therapy. Age < 50 years and HBV DNA ≥ 2000 IU/mL were independent risk factors for HBV DNA elevation. Conclusion HBV DNA elevation after resection increases the risk of HCC recurrence irrespective of preoperative antiviral therapy. However, HBV DNA elevation is an independent risk factor for recurrence in patients without preoperative antiviral therapy. Therefore, perioperative antiviral therapy should be considered to prevent HBV DNA elevation and recurrence, especially in patients with Age < 50 years and/or HBV DNA ≥ 2000 IU/mL.