Simvastatin in primary biliary cirrhosis: effects on serum lipids and distinct disease markers

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

“…1 Of note, statins may mediate antiinflammatory and immunomodulatory effects in other autoimmune disorders such as rheumatoid arthritis and multiple sclerosis. 30,37,38 In the present study, atorvastatin 10 mg/day significantly decreased IgM levels, but the changes were minimal. Antimitochondrial antibody titers, C-reactive protein, and fibrinogen remained unchanged, and higher statin doses no longer had a significant effect on IgM levels.…”

“…As such, statins could induce AP expression via activation of nuclear receptors such as the vitamin D receptor. 47,48 In contrast to Ritzel et al, 30 who reported an improvement of serum AP and ␥-glutamyltransferase levels, our study was restricted to patients with an incomplete biochemical response to UDCA who may represent a selected difficult-to-treat patient subpopulation. We focused on this patient group because such patients remain at increased risk for disease progression 5 and may be at the most urgent need for development of novel therapeutic regimens.…”

“…Our criteria for discontinuation (more than 2-fold above baseline) may be considered very stringent, but they were chosen given the lack of experience of statin therapy in patients with cholestatic liver diseases at the time of study initiation. Interestingly, serum aminotransferase elevations were not observed in PBC patients treated with simvastatin, 30 which may indicate a lower potential for hepatotoxicity of this drug. 24 However, the number of patients in the present and previous studies was too small for making final conclusions regarding drug tolerance in a rare condition such as PBC.…”

“…[16][17][18][19][20] Statins are generally well tolerated and are not associated with an increased risk of hepatotoxicity in patients with nonalcoholic fatty liver disease [21][22][23][24] or chronic hepatitis C. 25,26 However, limited data on safety of statins in chronic cholestatic liver diseases have been reported in small numbers of patients. [27][28][29][30] We have demonstrated previously in mice that atorvastatin stimulates the expression of genes involved in bile formation and thus ameliorates cholestasis as reflected by reduced serum bile acid levels in bile duct-ligated mice. 31,32 Additional beneficial effects of statins in cholestasis could result from a stimulation of bile acid metabolism, detoxification, and transport, which are predicted to counteract bile acid toxicity.…”

“…37,38 However, very little is known about the effects of statin therapy on cholestasis in PBC. [27][28][29][30] The aim of this study was to prospectively examine the effects of atorvastatin on serum markers of cholestasis, aminotransferases, and lipid and bile acid metabolism as well as inflammatory and immune markers in PBC patients with an incomplete biochemical response to UDCA.…”