BACKGROUND: Many previous studies have evaluated the histopathological features of tumours as risk factors for postoperative recurrence in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). However, there have been few large studies investigating the relationship between cyclooxygenase-2 (COX-2) expression in non-cancerous regions of the liver and postoperative recurrence in the remnant liver, especially in HBV-related HCC.OBJECTIVE: To evaluate the significance of COX-2 expression levels in noncancerous liver regions as a prognostic indicator of HCC in patients with HBV-related cirrhosis.METHODS: A total of 124 patients who underwent curative resection for HCC were reviewed retrospectively. Immunohistochemistry was used to evaluate the expression of COX-2 in noncancerous liver tissue. Clinicopathological variables were compared between patients with high COX-2 expression (n=58 [COX-2-positive group]) and patients with low COX-2 expression (n=66; [COX-2-negative group]). Univariate and multivariate analyses were performed to identify factors that affected disease recurrence.RESULTS: There was a significant correlation between COX-2 expression and alanine aminotransferase levels and vascular invasion. The recurrence-free survival rates in the COX-2-positive group were significantly lower than the rates in the COX-2-negative group. On multivariate analysis, the overexpression of COX-2 in noncancerous liver regions was found to be an unfavourable prognostic indicator for the recurrence of HCC.CONCLUSIONS: The results of the current study suggest that over-expression of COX-2 in noncancerous liver regions is an independent and significant indicator predictive of early recurrence of HCC in patients with HBV-related cirrhosis.