Supplementation of arachidonic acid plus docosahexaenoic acid in cirrhotic patients awaiting liver transplantation: a preliminary study.

BACKGROUND: In patients with cirrhotic liver diseases, supplementation of linoleic acid and alpha-linolenic acid often does not alter the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suggesting the necessity to directly provide these nutrients. METHODS: In a double-blind, placebo-controlled fashion, 9 cirrhotic patients listed for liver transplantation at Lahey Clinic Center were given daily supplementation with either 10 gel caps containing 500 mg of AA and 1000 mg of DHA (AA/DHA) or 250 mg of linolenic acid (LA) and 125 mg of oleic acid (OA; OA/LA) for 6 weeks. alpha-Tocopherol at 200 IU was provided daily. No other dietary prescription was made. Plasma fatty acid profiles were determined in triglyceride and phospholipids fractions. Plasma levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin 6 (IL-6), and soluble TNF receptor II (sTNFRII) were also measured. RESULTS: Four patients receiving OA/LA and 5 patients receiving AA/DHA completed the study without evidence of any adverse effects or intolerance. The supplementation of LA, AA, and DHA effectively raised their levels in either one or both plasma lipid fractions in this limited number of subjects. DHA plus AA also lowered 22:4omega-6, 22:5omega-6, and 22:5omega-3, suggesting that DHA reduced the elongation and desaturation of AA and EPA. CONCLUSIONS: It is feasible to improve the liver disease-associated deficiency of AA or DHA with modest intakes of AA and DHA. Whether this maneuver will affect the systemic inflammatory responsiveness and ultimately clinical outcome will require a large-scale and well-controlled intervention.

Cyclooxygenase-2 expression in hepatocellular carcinoma, cirrhosis and chronic hepatitis in the United States.

UNLABELLED: Aberrant expression of cyclooxygenase-2 in hepatocellular carcinoma was described in Asia. Using immunohistochemistry, we studied the expression of cyclooxygenase-2 in hepatocellular carcinoma, chronic hepatitis, and cirrhosis in a US institution. A staining score of 0-5 representing the sum of an intensity score and a distribution score was used. The mean scores were 2.2+/-1.60 for chronic hepatitis, 4.37+/-1.15 for cirrhosis, and 4.76+/-0.54 for hepatocellular carcinoma. We found a significant difference in mean staining scores between chronic hepatitis and cirrhosis (p < 0.0001), as well as between chronic hepatitis and hepatocellular carcinoma (p < 0.0001). Fibrosis correlated with cyclooxygenase-2 staining score (r=0.65). IN CONCLUSION: (1) Cyclooxygenase-2 expression is higher in cirrhosis and hepatocellular carcinoma when compared to chronic hepatitis. (2) Cyclooxygenase-2 expression correlates with the stage of fibrosis. (3) These results imply that in chronic hepatitis and possibly in cirrhosis, hepatocarcinogenesis may be a cyclooxygenase-2 dependent mechanism.