Alteration of prostaglandin metabolism in alcoholic liver disease: Its association with platelet dysfunction after chronic alcohol ingestion

Recently, hepatic microcirculation has been focused on as an important pathogenic factor in progression of alcoholic liver disease (ALD). Therefore, blood levels of several prostaglandins, which are associated with organ microcirculation, were determined in various liver diseases, including ALD. Blood thromboxane B₂ (TXB₂) level was significantly increased in ALD, when compared to other types of liver diseases, whereas both 6-keto prostablandin F_1α (6-keto PGF_1α) and prostaglandin E were not changed. These consequences resulted in the imbalance of 6-keto PGF_1α to TXB₂, which might promote platelet aggregation and blood vessel contraction. Indeed, the increase of β-thromboglobulin and platelet factor 4 in boood was observed in ALD. Furthermore, in ALD, the rate of arachidonate-induced platelet aggregation was prominently enhanced, and malondialdehyde production in platelet, which was well correlated with blood TXB₂ levels, significantly increased. Thus, the present study may indicate that, in ALD, hyper-aggregability of platelet is produced, because of the derangement of prostaglandin metabolism and platelet dysfunction.