Rapid changes in alcoholic hepatitis histology under steroids: correlation with soluble intercellular adhesion molecule-1 in hepatic venous blood.
OBJECTIVE
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 TNFalpha 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=0.55, P<0.01) and to lobular neutrophils (r=0.56, P<0.01). On steroids, sICAM-1 in hepatic vein and TNFalpha 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=0.68, P<0.01).


CONCLUSIONS
In severe AH under steroids, the short term histological improvement was associated with a decrease in circulating TNFalpha, a decrease in ICAM-1 expression, and correlated to hepatic vein sICAM-1 changes.
Spahr
L
L
Gastroenterology and Hepatology, University Hospital, 24, Rue Micheli-du-Crest 1211 Geneva 14, Switzerland. laurent.spahr@hcuge.fr
Rubbia-Brandt
L
L
Pugin
J
J
Giostra
E
E
Frossard
J L
JL
Borisch
B
B
Hadengue
A
A
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D001706:Biopsy; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006503:Hepatic Veins / Q000503:physiopathology*; D006519:Hepatitis, Alcoholic / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D022781:Hepatocytes / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics*; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D011239:Prednisolone / Q000627:therapeutic use*; D012044:Regression Analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D011239:Prednisolone; D001663:Bilirubin