Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid

Hepatology. 2007 Sep;46(3):776-84. doi: 10.1002/hep.21741.

Abstract

Statin therapy may target both hypercholesterolemia and cholestasis in primary biliary cirrhosis (PBC). However, little is known about the efficacy and safety of statins in PBC. The aim of this single-center study was therefore to prospectively examine the effects of atorvastatin on serum markers of cholestasis, aminotransferases, and lipid and bile acid metabolism as well as inflammatory and immunological markers in patients with PBC. Fifteen patients with early-stage PBC and an incomplete biochemical response to ursodeoxycholic acid (UDCA) therapy (defined as alkaline phosphatase 1.5-fold above the upper limit of normal after 1 year) were treated with atorvastatin 10 mg/day, 20 mg/day, and 40 mg/day for 4 weeks, respectively. Serum levels of alkaline phosphatase increased during atorvastatin 20 mg and 40 mg (P < 0.05), whereas leucine aminopeptidase and gamma-glutamyltransferase remained unchanged. No statistical differences in overall serum ALT, AST, bilirubin, and IgM levels were observed. However, atorvastatin was discontinued in 1 out of 15 patients because of ALT 2-fold above baseline, and 2 patients showed ALT elevations 3-fold above the upper limit of normal at the end of the atorvastatin treatment period. Serum total cholesterol and low-density lipoprotein cholesterol levels decreased by 35% and 49%, respectively (P < 0.001). Precursors of cholesterol biosynthesis (lanosterol, desmosterol, lathosterol) showed a similar pattern. No changes in serum bile acid levels and composition were observed during treatment.

Conclusion: Atorvastatin does not improve cholestasis in PBC patients with an incomplete biochemical response to UDCA but effectively reduces serum cholesterol levels.

MeSH terms

  • Adult
  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Biomarkers / blood
  • Cholagogues and Choleretics / therapeutic use
  • Cholestasis / complications
  • Cholestasis / drug therapy*
  • Cholesterol / blood*
  • Female
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Lipoproteins, LDL / blood
  • Liver Cirrhosis, Biliary / drug therapy*
  • Liver Cirrhosis, Biliary / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Single-Blind Method
  • Transaminases / blood
  • Ursodeoxycholic Acid / therapeutic use

Substances

  • Anticholesteremic Agents
  • Biomarkers
  • Cholagogues and Choleretics
  • Heptanoic Acids
  • Lipoproteins, LDL
  • Pyrroles
  • Ursodeoxycholic Acid
  • Cholesterol
  • Atorvastatin
  • Transaminases