Corticosteroids liver function

The conversion of prednisone to the biologically active corticosteroid prednisolone and the degree of plasma protein binding of prednisolone were studied in 22 patients with acute or chronic liver disease and in eight control subjects. In patients whose disease was active at the time of study, as judged by elevated serum levels of bilirubin and transaminase, significantly higher levels of plasma prednisolone were obtained after prednisolone administration than after equivalent doses of prednisone. In addition, the amount of unbound drug in the plasma was higher in patients with active disease. There was a significant correlation between the extent of plasma protein binding of prednisolone and the serum albumin concentration. Azathioprine did not affect the plasma binding of prednisolone in vitro. The plasma half-life of prednisolone was prolonged in two of three patients with chronic liver disease studied. These results suggest that in patients with acute hepatitis or active chronic liver disease there is impairment of reduction of the 11-oxo group of prednisone, and also impaired ring A reduction of prednisolone. Thus, incomplete conversion of prednisone to prednisolone occurs, which is a necessary step for biological activity; on the other hand there is also impairment of prednisolone degradation. These, together with low serum albumin concentrations which are associated with higher levels of circulating unbound prednisolone, result in quite different levels of biologically active corticosteroids compared with equivalent doses of prednisone or prednisolone in subjects without liver disease. The findings have important practical implications for the use of corticosteroids in patients with active liver disease.


Marina Ivančić, DVM
We are frequently asked about the serum chemistry profile changes that may be seen in dogs receiving corticosteroids. It is well-known that alkaline phosphatase (ALP) activity can (and usually does) increase. Increased ALP activity is due to both secretion from cellular membranes and induced synthesis (corticosteroid-induced isoenzyme) and can often reach more than 5,000 U/L. However, it appears to be less well-known that alanine transaminase (ALT), aspartate transaminase (AST), and even gamma-glutamyl transferase (GGT) activities can also increase after corticosteroid administration.

Genetic factors influence the susceptibility for advanced ALD. Monozygotic twins have a higher concordance rate for alcohol-related cirrhosis than dizygotic twins (23). Genetic factors may influence susceptibility to alcohol consumption or predisposition to development of ALD among those with AUD. Genes influencing the susceptibility for alcoholism include modifiers of neurotransmission such as γ-amino butyric acid and modifiers of alcohol metabolism such as alcoholic dehydrogenase and acetaldehyde dehydrogenase enzymes (24). The polymorphisms in these genes may be involved in an individual’s susceptibility to alcoholism, with wide allelic variation between different ethnic groups, but their role in the progression of ALD remains controversial. The second group of genes modifies the natural history of ALD through different mechanisms. Small candidate gene studies initially suggested a role for polymorphisms in genes encoding inflammatory mediators, endotoxin response and oxidative stress. However, larger studies including a recent genome-wide association study revealed that patatinlike phospholipase domain containing protein 3, may be the main genetic determinant of risk for and severity of ALD (25, 26). Phospholipase domain containing protein 3 is closely related with lipid metabolism and is also a risk factor for non-alcoholic fatty liver disease and HCC (26). The allele that negatively impacts disease progression (., rs738409) is more frequent within the Hispanic population, which is particularly sensitive to fatty liver diseases (25).

Corticosteroids liver function

corticosteroids liver function

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