Hepatic handling of vitamin D₃ in micronodular cirrhosis: A structure—function study in the rat

The response to vitamin D₃ (D₃) was studied in a model of micronodular cirrhosis induced by CCl₄. The uptake and C‐25 hydroxylation of D₃ were then studied in isolated‐perfused liver preparations. CCl₄‐treated rats had a significantly lower fractional hepatic D₃ uptake than controls; they also had lower 25‐hydroxyvitamin D₃ (25(OH)D₃) concentrations in both liver and perfusate following 150 min of perfusion. CCl₄ 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 CCl₄. Linear relationships were also observed between the V_v normal hepatocytes and the liver, perfusate, and total 25(OH)D₃, while the 25(OH)D₃ 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)D₃ is decreased in micronodular cirrhosis; they also indicate, however, that the D₃‐25 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)D₃ production by the cirrhotic rat liver.