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Prevention and Research

Statins in chronic liver disease

Perspective, 40 - 42
doi: 10.11138/PER/2013.2.2.040
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Statins are drugs widely used worldwide to treat hypercholesterolemia reducing cardiovascular risk. Clinical guidelines of the Adult Treatment Panel III (ATP III) represent an updating of previous evidence-based recommendations, on the assessment of cholesterol effects, stressing the importance of the reduction of its plasma levels. The benefits resulting from the use of statins are not only related to lipid-lowering but also to its pleiotropic effects, such as anti-inflammatory action.
Although, hepatotoxicity is a rare event (<2%), and often dose-related, in patients with liver disease fatal adverse effects have been reported using these molecules. The most important side effects consist of increased transaminase levels, abdominal
pain, muscle weakness, increased levels of creatinekinase, up to rhabdomyolysis. The factors responsible for myopathy, during treatment with statins, may be related to the patient characteristics (age, female sex, alcoholism, hypothyroidism, systemic diseases, family history of myopathy, high consumption of grapefruit juice, large physical activity, major surgery, etc.) or to interaction with other medications (fibrates, cyclosporine, antifungals, macrolides, protease inhibitors, nefazodone, amiodarone, verapamil, etc.). Statins are inhibitors of HMG-CoA reductase undergoing firstpass hepatic metabolism. Except pravastatin, other molecules of this class are subject to hepatic metabolism in phase 1 mediated by CYP 450 isoenzymes.
Therefore the indication for the use of HMG CoA reductase inhibitors must be evaluated by the physician on the basis of clinical necessity, and it is correct to start with low-dose drug administration, monitoring transaminases. Finally, it is appropriate to evaluate the drugs used simultaneously to statins that are metabolized at the level of the same cytochrome to reduce the risk of moderate and severe interactions. In fact the concomitant use of other drugs that are substrates of the same isoenzymes can determine the increase of statin concentration in the blood and consequently the risk of myopathy. The benefits associated with the use of statins in lowering cholesterol levels and preventing cardiovascular disease are superior to their potential risk of hepatotoxicity in patients with chronic liver disease. The use of statins in the course of liver disease is not absolutely contraindicated.
However, their administration is not recommended in the course of acute hepatitis and daily abuse of alcohol. The starting dose of statins should be as low as possible, by monitoring transaminase levels, initially every two weeks, then every month. It is important not to underestimate the risk that the concomitant use of other drugs may lead to increased serum liver enzyme cytonecrosis and consequently to an increased risk of myopathy.

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    doi: 10.11138/PER/2013.2.2.040