Statins Improve Liver Function, Reduce Cardiovascular Events in Patients With Abnormal Liver Tests

Contrary to widespread belief, patients with abnormal liver function who are given long-term statin treatment do not face an increased risk of liver disease….

In fact, statins can improve liver function in patients with abnormal liver tests. Moreover, this study is the first to show a substantially greater cardiovascular benefit in patients with abnormal liver function tests compared with patients who have normal liver tests.

These findings suggest that statins are a safe and promising treatment strategy for patients with non-alcoholic fatty liver disease (NAFLD).

A rare adverse effect of statin use is increased levels of liver enzymes or serum transaminases like alanine aminotransferase (ALT). As a result, many physicians are reluctant to prescribe statins to patients with elevated ALT.

The safety and efficacy of long-term statin treatment in patients with NAFLD is unclear. Previous small and short-term studies in patients with raised ALT levels because of NAFLD have suggested that they are safe and improve liver tests and liver histology.

To provide more evidence, Vasilis Athyros, MD, Hippokration University Hospital, Thessaloniki, Greece, and Dimitri Mikhailidis, MD, University College London, London, United Kingdom, conducted a post hoc analysis of the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study to assess whether long-term statin treatment (mainly atorvastatin) is safe and effective in patients thought to have NAFLD.

Of 437 patients with moderately abnormal liver tests (defined as less than 3x the upper limit of normal before beginning treatment), 227 were treated with a statin and 210 were not treated.

Overall, liver-related adverse effects occurred no more often in the group who were given statins. Over 3 years of follow-up, ALT improved or normalized in patients who were given statins, but in the group not taking statins liver tests worsened.

Importantly, patients who started the trial with abnormal liver function tests gained the greatest cardiovascular benefit of all — showing a 39% lower risk of having a cardiovascular event than patients in the GREACE study who had treated with a statin who had normal liver tests, and a 68% reduction in the relative risk of cardiovascular events compared with patients from GREACE who did not receive a statin.

The authors wrote, “The risk-to-benefit ratio of long-term statin treatment favors statin administration even for patients with moderately abnormal liver tests.”

Ted Bader, MD, University of Oklahoma Health Sciences Center, Oklahoma City, in an accompanying comment, said: “For too long, a raised ALT after starting a statin has been erroneously thought to represent liver disease. For too long, patients with liver disease have been denied statins for their hypercholesterolemia.”

“Despite the absence of liver injury from statins, a US survey showed that 50% of academic physicians would be reluctant to give a statin to a patient with an ALT of more than 1.5 times the upper limit of normal …10% to 30% of patients who need statins … would therefore be denied a statin,” he said. “Most physicians believe that statins cause liver disease because of the language of package inserts. Drug companies should be encouraged to request the deletion of this point from the insert.”

In advance of Publication Lancet Nov, 29, 2010