Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration

Abstract

Little is known about the effects of cholesterollowering agents in hypercholesterolemic patients with primary biliary cirrhosis (PBC). The aim of this study was to compare the changes induced by simvastatin and ursodeoxycholic acid (UDCA) on cholesterol metabolism in patients with PBC and preserved liver function. Six patients with PBC were administered simvastatin (40 mg/day) for 30 days and, after a washout period of 30 days, ursodeoxycholic acid (600 mg/day) for 30 days. Serum levels of lathosterol, campesterol, 7 ␣ -hydroxycholesterol, and 27-hydroxycholesterol were measured by gas chromatographymass spectrometry. During simvastatin administration, reduction of cholesterol levels (34% in 30 days) was paralleled by the decrease of lathosterol (55%), whereas concentrations of campesterol and of the two hydroxysterols were not substantially modified. During ursodeoxycholic acid administration, a trend toward a decrease of serum cholesterol concentrations was observed after only one year of treatment, and these changes were paralleled by the decrease of campesterol serum levels. Both simvastatin and UDCA were well tolerated, and a reduction of serum liver enzyme levels occurred with the latter. Simvastatin proved to be safe and effective in reducing serum cholesterol levels in patients with PBC by an inhibitory effect on cholesterol synthesis occurring within 24 h.

Metabolic Signature of Primary Biliary Cholangitis and Its Comparison with Celiac Disease

“…These differences seem to highlight opposite alterations in the lipid metabolism. PBC, indeed, is characterized by a marked increment of the enterohepatic circulation of various compounds, especially of lipid moieties, and several studies have demonstrated that cholesterol metabolism is markedly impaired for both synthesis and biliary elimination in PBC patients. , Conversely, not only are untreated celiac disease patients associated with lower concentrations of total cholesterol and high-density lipoprotein-cholesterol, but also, it seems that a reduction in serum HDL-C level is present even in the absence of gastrointestinal symptoms. , Therefore, HDL-C could be a key biomarker for the early diagnosis of CD and for the follow-up of the patients after gluten-free-diet treatment. − Nonetheless, the underlying mechanisms remain still poorly understood: intestinal malabsorption, reduction of the cholesterogenesis, reduction in cholesterol-transporting lipoproteins, decreased apolipoprotein (Apo)-AI secretion from the altered small bowel mucosa, increased biliary secretion, and high fecal elimination of cholesterol have all been proposed as explanations of this phenomenon. , …”

“…PBC, indeed, is characterized by a marked increment of the enterohepatic circulation of various compounds, especially of lipid moieties, and several studies have demonstrated that cholesterol metabolism is markedly impaired for both synthesis and biliary elimination in PBC patients. 1,39 Conversely, not only are untreated celiac disease patients associated with lower concentrations of total cholesterol and high-density lipoprotein-cholesterol, but also, it seems that a reduction in serum HDL-C level is present even in the absence of gastrointestinal symptoms. 40,41 Therefore, HDL-C could be a key biomarker for the early diagnosis of CD and for the follow-up of the patients after gluten-free-diet treatment.…”

Statins in Chronic Liver Disease: Review of the Literature and Future Role

“…141 Unsurprisingly, simvastatin use additionally decreased total cholesterol by at least 19% (p ¼ 0.01) and LDL by 26% (p ¼ 0.001). 141,142 In one RTC, while 12-month use of moderate-intensity simvastatin did significantly lower cholesterol and LDL (p ¼ 0.01), it did not significantly improve liver enzyme index or endothelial function, as measure by lipid hydroperoxides, cell adhesion molecule levels, antioxidant levels, inflammatory markers, and vascular compliance, compared with placebo even though positive trends were observed. 143…”