Response to antiviral therapy and hepatic expression of cyclooxygenases in chronic hepatitis C.
OBJECTIVE
The aims of this study were to investigate the expression of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) in chronic hepatitis C (CHC) by immunohistochemistry, based on the hypothesis that COXs expression could vary according to genotype, viral load, liver steatosis, BMI and response to therapy and to determine whether the addition of selective COX inhibitors could have a rationale in increasing the efficacy of antiviral therapy.


METHODS
We used 35 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsy from patients with CHC (17F/18M) with one of two types of genotype (1b and 3a). The presence of COX-1 and COX-2 in the cytoplasm of hepatocytes was scored on the basis of: (i) maximum intensity; (ii) dominant intensity; and (iii) extent.


RESULTS
No significant differences were found in COX-1 and COX-2 expression in CHC patients divided according to genotype or according to the type of response to combination therapy with pegylated-interferon and ribavirin. The only significant correlations were observed between the dominant intensity of COX-2 and the presence of histological steatosis (P<0.01) and an inverse correlation between COX-2 extent and the viral load (P<0.02).


CONCLUSIONS
The lack of correlation between COXs tissue expression and response to antiviral treatment suggests that there is no rationale to adding selective COX inhibitors to increase the efficacy of antiviral therapy, although further studies on larger patient populations are needed. On the contrary, there is a potential application for their use in the prevention and treatment of liver steatosis.
Department of Clinical Medicine and Emerging Pathologies, University of Palermo, Palermo, Italy. lydiagiannitp@libero.it
Lydia
L
Giannitrapani
Maurizio
M
Soresi
Sabrina
S
Ingrao
Emanuele
E
La Spada
Onofrio
O
Vuturo
Ada Maria
AM
Florena
Melchiorre
M
Cervello
Giuseppe
G
Montalto
D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D051545:Cyclooxygenase 1 / Q000032:analysis; D051546:Cyclooxygenase 2 / Q000032:analysis; D005260:Female; D015870:Gene Expression; D005838:Genotype; D016174:Hepacivirus / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis*; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D013194:Staining and Labeling; D016896:Treatment Outcome
D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases