Background: It has been suggested that the elevation of serum hyaluronate (
HA) levels in liver diseases may be due to increased synthesis of HA by hep
atic stellate cells or decreased degradation by sinusoidal endothelial cell
s. The increase in serum HA levels in patients with cirrhosis is thought to
be a response to a reduction in HA receptors (CD44) in hepatic sinusoidal
endothelial cells. To learn more about how alcohol affects the number and d
istribution of HA receptors of hepatic sinusoidal endothelial cells, we imm
unohistochemically studied CD44 levels in liver biopsy obtained from patien
ts with alcoholic liver disease (ALD patients) and also from patients with
nonalcoholic liver disease (non-ALD); ALD patients were evaluated when they
were currently drinking and again after they became abstinent. Normal live
r tissue obtained from three autopsy cases served as a control.
Methods: Liver biopsy specimens were obtained from 18 ALD patients and 12 n
on-ALD patients. In ALD patients, liver biopsy was performed twice within 3
days and 4 to 8 weeks after abstinence when serum levels of aspartate amin
otransferase and alanine aminotransferase became normal. CD44 in liver spec
imens was stained with anti-CD44 antibody by streptavidine-biotin-peroxidas
e complex. The intensity of the staining of CD44 in liver tissue was determ
ined by a computer-assisted imaging analyzer. We also measured serum levels
of CD44 in both ALD and non-ALD patients.
Results: The intensity and the number of CD44 staining increased in both AL
D and non-ALD patients compared with those in normal liver, which was negat
ive. The staining intensity of CD44 in liver specimens obtained from patien
ts with ALD who were active in alcohol consumption were significantly highe
r when compared with patients with ALD after abstinence. Serum levels of CD
44 in patients with liver disease increased compared with those of healthy
subjects.
Conclusions: The results suggest that HA receptors may increase to degrade
the increased HA in serum and/or liver.