Influence Of Serum HBV-DNA Level On Recurrence Of Small Hepatocellular Carcinoma After Curative Resection

Objective: Virus infections have close relations with primary hepatocellular carcinoma. Some researchers abroad have reported that high level of serum HBV DNA or chronic active hepatitis B is one of risk factors for hepatocellular carcinoma recurrence. Meanwhile, little similar research has been conducted domestically. Method: 109 cases of small hepatocellular carcinoma after curative resection were entered into this study between 2000 and 2004. Serum HBV-DNA was quantitatively detected using Real-time quantitative polymerase chain reaction(RTQ–PCR) during the follow-up. All the cases were divided into high or low group according to viral load. The value of serum HBV-DNA from the patients was 1.0 ×10~5 copies/ml or greater, the patients were assumed to have a high virus load. Tumor-free rate was compared between the two groups, and furthermore, undertaken by stratum analysis in term of recurrence time after operation (≤2 years or >2 years after operation). To verify the recurrence factors for small hepatocellular carcinoma after curative resection, the patients'clinical features, laboratory test results and pathologic findings were investigated by multifactorial and monofactorial analyses using Cox's proportional hazard model. Results: The 1-, 2-, 3-, and 4-year overall cumulative recurrence rates after operation were 7.5%, 26.6%, 52.8%, and 63.3%, respectively. The cumulative recurrence rates at 1, 2, 3 and 4 years in the high viral load group were 7.5%, 26.6%, 52.8%, 63.3%,respectively; and in the low viral load group, 9.68%, 22.4%, 22.4%, 28.9%, respectively。Student's t-test showed that the mean values of serum ALT (alanine aminotransferase) and AST (aspartate aminotransferase) in the high viral load group were higher than those in the low viral load group (p = 0.035 and p = 0.032, respectively). Moderate correlations were found between the value of serum HBV-DNA and serum ALT and AST (correlation coefficients of 0.448 and 0.554, respectively). The serum viral immunological makers were not significantly different between the groups. The mean values of serum HBV-DNA copies had no statistical significance between the groups of HBsAg (+) versus HBsAg(-) and HBeAg(+) versus HBeAg(-) (p = 0.380 and p = 0.505, respectively). The overall tumor-free rates had no statistical difference between high and low viral load group (p = 0.4286), but the stratum analysis identified that tumor-free rates of over 2 years after resection were significantly different between the two groups (p = 0.0065). Multifactorial analysis showed that high viral load of serum HBV-DNA was the only recurrence risk factor for the patients with tumor-free time more than 2 years after resection, and tumor location, pathologic grade and tumor nodule were independent recurrence risk factors for all the patients. Conclusions: Serum HBV-DNA load has significant influence on small hepatocellular carcinoma recurrence after curative resection for the patients with tumor-free time over 2 years after operation. The value of Serum HBV-DNA should be quantitatively detected with liver function in patients with hepatocellular carcinoma. In addition, it may be necessary to apply anti-viral therapy to the patients with high level of serum HBV-DNA.