Management of raised ALT/AST secondary to statin use

Management of raised transaminases (ALT,AST) associated with statin treatment (1,2,3):

• statin product information recommends baseline measurement of liver function and contraindicates the drugs in active liver disease
  • in patients with baseline liver abnormalities, active disease must first be excluded
  • at standard doses, effects on liver enzymes are rare (<1%), but at higher doses different statins vary in the degree to which they raise liver enzymes
    • may just parallel their LDL cholesterol-lowering efficacy, or could be some specific hepatotoxic effect of particular statins. A logical approach is to increase the statin dose slowly in those at risk of transaminase rises
    • routine monitoring of liver function after starting statin treatment is no longer recommended for simvastatin or pravastatin to 40 mg daily (since the extensive controlled trial data are reassuring), but remains recommended in product information for the other statins and higher doses, despite the lack of evidence of adverse outcomes
  • if alanine or aspartate transaminsases are more than three times the upper limit of normal in an asymptomatic patient with no other liver abnormalities, the enzymes should be checked within a week and statin treatment stopped temporarily if alanine transaminase is still at this level
  • increases to between two to three times the upper limit of normal in an asymptomatic patient necessitate monitoring, but will often resolve while on treatment
  • initiation of statin treatment in patients with raised baseline ALT
    • most of the randomised trials excluded patients with transaminase levels more than 1·2, 1·5 or 2 times the upper limit of normal, and so the safety of statins in these people has not been systematically assessed
      • if statin therapy is indicated in patients whose alanine or aspartate transminase are abnormal but stable over a few months, and who have no other evidence of active disease, it may be reasonable to start statin treatment with monitoring at intervals (eg, 3 and 6 months) but with continued treatment if transaminases remain stable
        • non-alcoholic steatohepatitis (fatty liver) may possibly improve with lipid-lowering therapy and no evidence has been found suggesting worsened outcome among people with raised enzymes from hepatitis B or C
        • if other liver function tests such as bilirubin are abnormal or the enzymes are suggestive of an obstructive picture, statin therapy should generally be avoided until further investigation is undertaken
  • if new-onset liver disease in a patient receiving ongoing statin therapy
    • hepatology opinion (1) suggests that:
      • once a systematic and complete medical evaluation reveals significant liver disease in a patient receiving statin therapy, the aetiology should be established. If a causal relation between significant liver injury and statin therapy cannot be excluded, then reinitiation of statin therapy is not recommended and alternative lipid-lowering strategies should be considered
    • however note also that a review stated that (2):
      • risk of statin-associated liver enzyme elevations or muscle injury is not related to the magnitude of LDL-C lowering but is more likely determined by drug- and dose-specific effects
    • more aggressive statin therapy increases the incidence of transaminase elevations in clinical trials versus lower intensity therapy. Increases in transaminases may be more problematic when hydrophilic statins are used aggressively, whereas CK elevations are more problematic with higher intensity lipophilic statin therapy (3)

Reference:

• (1) Alsheikh-Ali AA et al. Effect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer: Insights From Large Randomized Statin Trials Journal of the American College of Cardiology 2007;50 (5): 409-418.
• (2) Dale KM et al. Impact of statin dosing intensity on transaminase and creatine kinase. Am J Med. 2007 Aug;120(8):706-12
• (3) Armitage J. The safety of statins in clinical practice The Lancet, Volume 370, Issue 9601, 24 November 2007-30 November 2007, Pages 1781-1790