HYPERHYALURONANEMIA IN ALCOHOLIC HEPATITIS IS ASSOCIATED WITH INCREASED LEVELS OF CIRCULATING SOLUBLE INTERCELLULAR-ADHESION MOLECULE-1

The purpose of this study was to evaluate the role of the sinusoidal e ndothelial cell (SEC) during the clinical course of alcoholic hepatiti s. Twenty consenting patients (mean age: 49.4 +/- 11.0 years) with mod erate or severe hepatitis were studied. The patients were selected and characterized according to their history of drinking and laboratory p rofile, including serum aminotransferases, bilirubin, total white bloo d 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 lev els of soluble intercellular adhesion molecule (sICAM)-1 over a 6-mont h observation period. All patients were hospitalized for the first mon th and encouraged to abstain from drinking for the duration of the stu dy. The initial increased levels of both hyaluronan (542 +/- 32 ng . m l(-1) serum) and sICAM-1 (488 +/- 70 ng . ml(-1) serum), gradually fel l during the 6-month observation period, eventually reaching values cl ose to those seen in healthy subjects. A positive correlation was obta ined between changes in these two markers of SEC function/activation o n the one hand, and between these two tests and bilirubin, on the othe r hand. These data indicate that abnormalities of SEC function/activat ion, as reflected by serum hyaluronan and sICAM-1, are prominent in al coholic hepatitis, and these alterations improve within relatively sho rt periods of time after cessation of alcohol consumption.