Hepatic handling of vitamin D 3 in micronodular cirrhosis: A structure—function study in the rat

The response to vitamin D 3 (D 3 ) was studied in a model of micronodular cirrhosis induced by CCl 4 . The uptake and C‐25 hydroxylation of D 3 were then studied in isolated‐perfused liver preparations. CCl 4 ‐treated rats had a significantly lower fractional hepatic D 3 uptake than controls; they also had lower 25‐hydroxyvitamin D 3 (25(OH)D 3 ) concentrations in both liver and perfusate following 150 min of perfusion. CCl 4 induced a wide spectrum of hepatic morphologic changes ranging from mild to large collagen infiltration, but micronodular cirrhosis was present in more than 90% of the animals. Histomorphometric analysis of the liver indicated an overall highly significant increase in the volume density (V v ) of collagen infiltration, and a reduction in the V v normal hepatocytes following CCl 4 . Linear relationships were also observed between the V v normal hepatocytes and the liver, perfusate, and total 25(OH)D 3 , while the 25(OH)D 3 production decreased in a logarithmic fashion as the collagen infiltration of the liver parenchyma increased. These data show that the overall production of 25(OH)D 3 is decreased in micronodular cirrhosis; they also indicate, however, that the D 3 ‐25 hydroxylase seems to stay unimpaired in the remaining hepatocytes of the diseased liver, and that the V v normal hepatocytes constitute one of the major determinants of the 25(OH)D 3 production by the cirrhotic rat liver.