Expression of cyclooxygenase‐2 in chronic hepatitis B and the effects of anti‐viral therapy

Backgound: Cyclooxygenase‐2 may play a role in the development of hepatocellular carcinoma, but the relationship between cyclooxygenase‐2 and chronic hepatitis B is unknown. Aim: To investigate the expression and cellular localization of cyclooxygenase‐2 in chronic hepatitis B patients and the effects of anti‐viral therapy. Methods: Using immunohistochemistry, in situ hybridization, Western blot and reverse transcription polymerase chain reaction, protein and messenger RNA expression and cellular localization of cyclooxygenase‐2 in 35 chronic hepatitis B patients were assessed. Fourteen histologically normal and non‐viral‐infected livers were used as controls. The cyclooxygenase‐2 immunoreactivities of paired liver biopsies from 12 patients receiving anti‐viral therapy were compared. Results: Immunohistochemistry and in situ hybridization revealed that cyclooxygenase‐2 expression was confined to hepatocytes. Patients with chronic hepatitis B had significantly higher cyclooxygenase‐2 expression compared with controls. The cyclooxygenase‐2 expression of hepatitis B e antigen‐positive and ‐negative chronic hepatitis B patients was not significantly different, although the necro‐inflammatory activity of the latter group was significantly lower. Over‐expression of cyclooxygenase‐2 in patients with chronic hepatitis B was further confirmed by Western blot and reverse transcription polymerase chain reaction. Twelve hepatitis B e antigen‐positive chronic hepatitis B patients received anti‐viral therapy: lamivudine in seven and interferon in five. Despite hepatitis B e antigen seroconversion, disappearance of hepatitis B virus DNA in serum, normalization of liver enzymes and a significant reduction in necro‐inflammatory activity in all 12 patients, no significant change in cyclooxygenase‐2 expression was found. Conclusions: Chronic hepatitis B is associated with elevated cyclooxygenase‐2 levels in hepatocytes, and the over‐expression of this enzyme does not reflect inflammatory activity. Up‐regulation of cyclooxygenase‐2 persists after successful anti‐viral therapy.