HEPATIC STELLATE CELLS AND LIVER RETINOID CONTENT IN ALCOHOLIC LIVER-DISEASE IN HUMANS

Body retinoids are stored in the lipid droplets of hepatic stellate (I to) cells. In chronic liver disease, the stellate cells differentiate into myofibroblast-like cells, a process whereby they lose their retin oid-containing lipid droplets. We studied the relation between liver r etinoid content, the number of lipid droplets per stellate cell, and t he number of stellate cells per mm(2) in human alcoholic liver disease , Semithin sections of liver biopsies from normal subjects and patient s with early (steatosis, inflammation, and mild fibrosis) and late (ci rrhosis and cirrhosis with acute alcoholic hepatitis) alcoholic liver disease were morphometrically evaluated. Liver retinoid content was de termined by HPLC. In normal patients, liver retinoid content was 901 /- 213 IU/g of liver (mean +/- SEM), There was a decrease in liver ret inoid content in early alcoholic liver disease (409 +/- 50 IU/g) and a further reduction in cirrhosis (153 +/- 50 IU/g). In patients with ac ute alcoholic hepatitis, retinoid content was strikingly low (5.2 +/- 1.8 IU/g), There was a progressive decrease in the number of stellate cells per mm(2) associated with progressive liver damage. We found a f air correlation between the number of stellate cells per mm(2) and liv er retinoid content in all patient groups (overall correlation: 0.71). In normal subjects, the mean number of lipid droplets per stellate ce ll was 7.4 +/- 0.7. In patients with early alcoholic liver disease and in patients with alcoholic cirrhosis, this value was increased to 13. 6 +/- 0.8 and 10.4 +/- 2.0, respectively. In patients with acute alcoh olic hepatitis, only a few lipid droplets were present (4.2 +/- 0.5). There was a good correlation between liver retinoid content and mean n umber of lipid droplets in normal patients (r = 0.58). In alcoholic ci rrhosis, however, correlation was poor (r = 0.34). In early alcoholic liver disease, the correlation was absent (r = 0.004). In conclusion, the major finding of our study is that the correlation between the mea n number of lipid droplets per stellate cell and liver retinoid conten t varies according to the hepatic pathology considered. Marked lipid d roplet accumulation occurs in stellate cells in early alcoholic liver disease and, to a lesser extent, in alcoholic cirrhosis, but there is no correlation between the mean number of lipid droplets per stellate cell and liver retinoid content. Therefore, not retinoids but probably lipids are responsible for the accumulation of lipid droplets. We als o find that there is a fair correlation between the number of stellate cells per mm(2) and liver retinoid content in all patient groups. Fin ally, we confirm the decrease in hepatic retinoid content that occurs in alcoholic liver disease in humans, even af:the early stages of the disease.