Hyperlipidemia occurs in the majority of patients with primary biliary cirrhosis. It is not uncommon for the diagnosis to be made as a consequence cholesterol screening tests.
Although serum cholesterol and triglycerides are both raised there is no evidence that these abnormalities are associated with an increased cardiovascular risk. One explanation for this paradox is that elevated HDL levels and reduced levels of lipoprotein A, both of which are characteristic of early stages of the disease, protect against atherosclerosis. Whereas reduced cholesterol synthesis and absorption in advanced PBC outweigh the effects of reduced biliary secretion.
An alternative explanation is that most cholesterol in PBC is localized within lipoprotein X, a unique lipoprotein associated with obstructive jaundice which does not confer the same cardiovascular risk as LDL.
The question then arises is it worth treating hyperlipidemia in PBC? Ursodeoxycholic acid and HMG CO-A reductase inhibitors are both well-tolerated in PBC and reduce serum cholesterol levels, but there are no data to show this leads to a reduction in cardiovascular risk. However, the ability of ursodeoxycholic acid therapy to reduce serum cholesterol and improve xanthelasma is a further indication for its use in PBC.
Although current data do not suggest a specific cardiovascular indication to treat hypercholesterolemia in PBC, given the safety of statins it would seem prudent to carefully assess other cardiovascular risk factors and to have a low threshold for introducing a statin in addition to UDCA. Simvastatin has been shown to be safe in PBC and is therefore a good first choice.
Finally it is important that further studies are carried out to determine exactly what the cardiovascular risk is in PBC and whether lipid-lowering therapy confers a benefit in this group of patients.
David H Adams, Liver Research Laboratories, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, England
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