Overexpressed cyclo-oxygenase-2 in the background liver is associated with the clinical course of hepatitis C virus-related cirrhosis patients after curative surgery for hepatocellular carcinoma.
BACKGROUND
The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC.


METHODS
Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53-73 years; follow-up period; range 22-159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin-biotin-peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery.


RESULTS
The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann-Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann-Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival.


CONCLUSIONS
Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.
Morinaga
Soichiro
S
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Asahikum, Japan. morinagas@kcch.jp
Tarao
Kazuo
K
Yamamoto
Yuji
Y
Nakamura
Yoshiyasu
Y
Rino
Yasushi
Y
Miyakawa
Kaoru
K
Ohkawa
Shinichi
S
Akaike
Makoto
M
Sugimasa
Yukio
Y
Takemiya
Shoji
S
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000209:etiology / Q000601:surgery; D051546:Cyclooxygenase 2 / Q000097:blood*; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006526:Hepatitis C / Q000150:complications* / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008103:Liver Cirrhosis / Q000150:complications / Q000201:enzymology* / Q000821:virology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015854:Up-Regulation
D051546:Cyclooxygenase 2