Cyclooxygenase-2 expression in chronic hepatitis C and the effect of interferon alpha treatment.
OBJECTIVE
Cyclooxygenase-2 (COX-2), a target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), is upregulated in chronic hepatitis B and may have a role in hepatocellular carcinoma. Little is known about the expression of COX-2 in chronic hepatitis C (HCV) infection. The aim the present study was to evaluate the extent of COX-2 expression in liver biopsies in patients with HCV infection and to determine the effect of treatment with interferon alpha (IFN).


METHODS
Percutaneous liver biopsy specimens were retrieved. Following formalin fixation and paraffin embedding, the biopsies were histologically evaluated for inflammation and fibrosis. The extent of COX-2 expression was measured by the avidin biotin immunohistochemical technique using a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according to the number of hepatocytes expressing COX-2. Data were analyzed using Student's t-test.


RESULTS
Liver biopsies from 10 patients before and after treatment with IFN were obtained and compared with nine normal liver biopsies. All of the liver biopsies showed some COX-2 expression. COX-2 expression was confined to hepatocytes and bile duct epithelium and was not detected in vascular endothelium or inflammatory cells. The extent of COX-2 expression was greater in hepatitis C infected liver biopsies than in normal biopsies. Following treatment with IFN, there was a greater than threefold reduction in COX-2 expression (P < 0.01). This result was independent of the sustained virological response.


CONCLUSIONS
In this small pilot study we have shown that COX-2 is overexpressed in liver biopsies infected with HCV and COX-2 expression is reduced following treatment with IFN.
Manning
Diarmuid S
DS
Department of Clinical Pharmacology/Gastroenterology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland.
Sheehan
Katherine M
KM
Byrne
Michael F
MF
Kay
Elaine W
EW
Murray
Frank E
FE
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome; D015854:Up-Regulation
D000998:Antiviral Agents; D016898:Interferon-alpha; D051546:Cyclooxygenase 2