Methylprednisolone administration in primary biliary cirrhosis increases cholic acid turnover, synthesis, and deoxycholate concentration in bile.
As immunosuppressive agents, corticosteroids may be considered an appropriate treatment for primary biliary cirrhosis, even if bone loss and other side effects may occur. We studied biliary lipid metabolism in 10 nonicteric patients, with histologically proven primary biliary cirrhosis (stage I-IV). We administered methylprednisolone (24 mg daily) for 30 days to ascertain its effects on biliary lipid metabolism, which are largely still unknown. All patients underwent a 30-day drug-washout period before entering the trial. The following parameters were studied before and after methylprednisolone treatment: serum biochemistry; cholic acid pool size, kinetics and synthesis; biliary lipid secretion; biliary bile acid pattern; biliary lipid molar percentage; and cholesterol saturation index. Methylprednisolone induced a statistically significant (Wilcoxon rank test) increase in cholic acid turnover (from 0.26+/-0.04 to 0.50+/-0.05 K/day, P = 0.005) and synthesis (from 0.42+/-0.12 to 0.78+/-0.11 mmol/day, P = 0.04), and in bile deoxycholic acid molar percentage (from 19.4+/-2.7 to 30.6+/-4.4% molar, P = 0.01). On the other hand, a significant decrease in biliary cholesterol molar percentage (from 7.9+/-0.7 to 6.4+/-0.5% molar, P = 0.005), cholesterol saturation index (from 1.11+/-0.11 to 0.95+/-0.07, P = 0.05), and biliary cholesterol secretion (from 64.7+/-5.4 to 53.0+/-4.5 micromol/hr, P = 0.005) was observed. These findings show that short-term administration of methylprednisolone in patients with primary biliary cirrhosis does not induce expansion of the cholic acid pool but increases cholic acid synthesis and turnover, as well as intestinal production of deoxycholic acid. If long-term treatment is considered, the beneficial immunosuppressive effects of corticosteroids have to be weighed against the hepatotoxic properties of deoxycholic acid.
Mazzella
G
G
Department of Internal Medicine and Gastroenterology, University of Bologna, Italy.
Fusaroli
P
P
Pezzoli
A
A
Azzaroli
F
F
Mazzeo
C
C
Zambonin
L
L
Simoni
P
P
Festi
D
D
Roda
E
E
D000328:Adult; D000368:Aged; D001646:Bile / Q000737:chemistry*; D002784:Cholesterol / Q000032:analysis; D002793:Cholic Acids / Q000378:metabolism* / Q000493:pharmacokinetics; D003840:Deoxycholic Acid / Q000032:analysis*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000378:metabolism*; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged
D002793:Cholic Acids; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003840:Deoxycholic Acid; D002784:Cholesterol; D008775:Methylprednisolone