Rapid changes in alcoholic hepatitis histology under steroids: correlation with soluble intercellular adhesion molecule-1 in hepatic venous blood q Laurent Spahr 1, * , Laura Rubbia-Brandt 2 , Je ´ro ˆme Pugin 3 , Emile Giostra 1 , Jean-Louis Frossard 1 , Bettina Borisch 2 , Antoine Hadengue 1 1 Gastroenterology and Hepatology, University Hospital, 24, Rue Micheli-du-Crest1211 Geneva 14, Switzerland 2 Clinical Pathology, University Hospital, Geneva, Switzerland 3 Medical Intensive Care Unit Laboratory, University Hospital, Geneva, Switzerland Background/Aims: In alcoholic hepatitis (AH), enhanced expression of intercellular adhesion molecule-1 (ICAM-1) correlates to neutrophil infiltration and histology. In severe AH under steroids, the evolution of the hepatocyte membranous ICAM-1 expression and its soluble form (sICAM-1) is not known. Methods: Twenty-six consecutive patients with biopsy-proven severe AH had liver tissue studies for hepatocyte membranous ICAM-1 expression by immunostaining. Lobular neutrophils (mean per high power field) were counted after chloracetate esterase staining. Histological damage was assessed semiquantitatively. Circulating levels of sICAM- 1 and TNFa in peripheral and hepatic vein were measured using immunoassays. After 8 days on steroids, 19 patients had repeat biopsy. Results: At baseline, hepatocyte membranous ICAM-1 correlated both to histology (r ¼ 0.55, P , 0.01) and to lobular neutrophils (r ¼ 0.56, P , 0.01). On steroids, sICAM-1 in hepatic vein and TNFa in both vascular beds decreased. Hepatocyte membranous ICAM-1 and hepatocellular damage decreased, but lobular neutrophils increased. Changes in sICAM-1 in hepatic vein correlated to histological changes (r ¼ 0.68, P , 0.01). Conclusions: In severe AH under steroids, the short term histological improvement was associated with a decrease in circulating TNFa, a decrease in ICAM-1 expression, and correlated to hepatic vein sICAM-1 changes. q 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. Keywords: Alcoholic hepatitis; Intercellular adhesion molecule; Cytokine; Tumor necrosis factora; Corticosteroids; Liver biopsy; Neutrophil; Inflammation; Hepatocellular damage; Cirrhosis; Immunostaining; Histology; Hepatic vein 1. Introduction Alcoholic hepatitis (AH) is histologically defined as an infiltration of the liver lobule with a cellular infiltrate in which polynuclear neutrophils are predominant [1]. Addi- tional features include hepatocyte ballooning and necrosis, Mallory bodies, canalicular cholestasis, and fatty infiltration with a macro- and microvesicular pattern [2]. The pathogen- esis of AH is incompletely understood. However, an impor- tant role for an immune-mediated inflammatory reaction is suggested by the presence of elevated circulating levels of cytokines such as tumor necrosis factor-a (TNFa) [3–6] or interleukin-8, a potent neutrophil activator [7]. Corticosteroids reduce the 1-year mortality in patients with severe biopsy-proven AH, as defined by a discriminant function of more than 32 and/or the presence of hepatic encephalopathy [8–10]. The beneficial effect of corticoster- oids in these patients could be associated with a down regu- lation both in proinflammatory cytokines production and neutrophils activation status [11]. Journal of Hepatology 35 (2001) 582–589 0168-8278/01/$20.00 q 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. PII: S0168-8278(01)00190-8 www.elsevier.com/locate/jhep Received 26 April 2001; received in revised form 18 July 2001; accepted 26 July 2001 q Meeting presentation: Presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD), Dallas, November 1999. * Corresponding author. Tel.: 141-22-3729340; fax: 141-22-3729366. E-mail address: laurent.spahr@hcuge.ch (L. Spahr).