Hyperhyaluronanemia in alcoholic hepatitis is associated with increased levels of circulating soluble intercellular adhesion molecule-1

Abstract

The purpose of this study was to evaluate the role of the sinusoidal endothelial cell (SEC) during the clinical course of alcoholic hepatitis. Twenty consenting patients (mean age: 49.4 +/- 11.0 years) with moderate or severe hepatitis were studied. The patients were selected and characterized according to their history of drinking and laboratory profile, including serum aminotransferases, bilirubin, total white blood cell and neutrophil count, and prothrombin times. C-reactive protein and interleukin-6 were also measured as markers of the hepatic acute phase response. A marker of the SEC functional state, the circulating level of hyaluronan, was measured in parallel with the circulating levels of soluble intercellular adhesion molecule (sICAM)-1 over a 6-month observation period. All patients were hospitalized for the first month and encouraged to abstain from drinking for the duration of the study. The initial increased levels of both hyaluronan (542 +/- 32 ng x ml(-1) serum) and sICAM-1 (488 +/- 70 ng x ml(-1) serum), gradually fell during the 6-month observation period, eventually reaching values close to those seen in healthy subjects. A positive correlation was obtained between changes in these two markers of SEC function/activation on the one hand, and between these two tests and bilirubin, on the other hand. These data indicate that abnormalities of SEC function/activation, as reflected by serum hyaluronan and siCAM-1, are prominent in alcoholic hepatitis, and these alterations improve within relatively short periods of time after cessation of alcohol consumption.