Statins are apparently safe for people with non-alcoholic fatty liver disease (NAFLD), according to an expert who conducted a review of the medications' safety.1
Cholesterol Collapse
The drugs fall into a class of medications designed to lower cholesterol by blocking the liver's production of it. There are currently five statin drugs on the market in the United States. They lower levels of the so-called "bad" cholesterol (low-density lipoprotein or LDL-C) by blocking the action of an enzyme that plays a role in the production of cholesterol in the body. Statins also boost the liver's ability to remove LDL-C already in the blood. In studies testing the efficacy of these drugs, cholesterol was lowered up to 60%, on average, in patients. Research has also shown that the drugs reduce elevated levels of triglycerides and produce a modest increase in the "good" cholesterol, or high-density lipoprotein (HDL-C).2
Lowering cholesterol is one strategy toward preventing heart disease since the substance can damage blood vessels and boost the risk of having a heart attack or chronic heart failure.3
"Statins are among the most widely prescribed medications in the Western world," wrote Naga Chalasani, MD, in the division of Clinical Pharmacology at Indiana University School of Medicine in the journal Hepatology. "Their benefit in the primary and secondary prevention of cardiovascular disease is unequivocal."
Despite this, increases in liver enzymes are common in people who take the drugs, Chalasani stated. These enzymes are released by the liver into the bloodstream when it is damaged or diseased.4 As such, doctors test for them to determine if liver disease is present in their patients. Therefore, physicians are advised to routinely monitor the liver conditions of the patients taking statins.
Statins' Effect on the Liver
To understand the effect of statins on liver function more thoroughly, particularly in those with NAFLD, Chalasani reviewed past studies of the drugs. He found that increases in liver enzymes associated with their use occur in a small minority of patients, similar to the numbers of patients treated with non-therapeutic placebos in clinical trials.
"Very rarely, after initiating statins, the liver enzymes can rise to significantly higher levels with no evidence of liver dysfunction," Chalasani wrote. He cited a very large meta-analysis (analysis of a series of previous research) involving nearly 50,000 patents that found statin use was not associated with significantly higher levels of enzymes compared to those on placebo.5 This suggests that people with high blood lipids may experience spontaneous fluctuations in their liver enzymes, regardless of whether or not they are taking statins, he pointed out.
Statins: Not Risky for NAFLD Patients?
Next, Chalsani wanted to better understand the effect of statins in people with NAFLD. He noted there have been rare reports of significant liver injury associated with statin use.
While the drugs are not recommended for those with active liver disease, it is unclear whether those with NAFLD can take them safely, he wrote. "Irreversible liver damage leading to death or liver transplantation appears to be extremely uncommon with statins, especially when one considers the magnitude of their use worldwide," wrote Chalasani. This is important to consider, he stressed, because these patients commonly have high cholesterol levels and their liver condition may create a high cardiovascular risk that could be treated using statins.
After reviewing the medical literature, Chalasani found little information relative to NAFLD. "But the existing data provide some evidence that they can be used safely," he wrote. Chalasani's own studies of people with high blood lipids and elevated liver enzymes found that they are not at higher risk of liver toxicity compared with hyperlipidemic patients with normal liver enzymes.
Chalsami also examined the results of two small, previously published studies.6,7 In one study, a statin drug was given to five patients with non-alcoholic steatohepatitis (NASH), a form of advanced fatty liver disease that causes liver inflammation. Liver enzymes returned to normal in all patients and there was some improvement in liver fat and inflammation. In the second study, seven patients with NASH received a statin medication. Similarly, liver function was improved by the end of the nearly 2-year study.
Statins and Liver Cancer Risk
Further, Chalasani studied the risk of liver cancer related to statin use. Animal studies had suggested there might be such a risk, he wrote. "Although this is a very important question," he wrote, "data are sparse and studies to address this question are difficult to design and conduct."
He cited one very large meta-analysis of studies involving more than 30,000 patients that found no increased risk of cancer caused by the drugs.8 While the follow-up period in this study was too short to determine any long-term risk, Chalasani also cited a trial with 10 years of patient follow-up that likewise did not show any increased cancer risk.9
Other studies have suggested an increased risk of developing a condition known as rhabdomyolysis (rab-doh-my-AAL-uh-sis) in statin use. The illness is characterized by muscle cell destruction, and can occur in people with metabolic dysfunction in the liver due to cirrhosis, though the association hasn't been studied extensively, Chalasani wrote.
Contrasting Conclusions
Based on his findings, Chalasani contends that recommendations to monitor liver function in people taking statins remains controversial, and "require further review". The controversy exists because it appears elevated liver enzymes don't necessarily indicate underlying steatosis, and yet those with advanced fibrosis/cirrhosis may have completely normal enzyme levels, he wrote.
Nonetheless, he doesn't write off the benefit of statins in people with fatty liver disease. "Importantly, there is no sound rationale why statins should not be used in patients with chronic liver disease who otherwise need statin therapy," he concluded.
Last year, Chalasani served as a consultant to Merck, manufacturer of two statin drugs: lovastatin and simvastatin.
1. Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 2005 Apr;41(4):690-5.
2. National Heart, Lung and Blood Institute. National Institutes of Health. Statins. Available at: http://nhlbisupport.com/chd1/meds1.htm. Accessed June 15, 2005.
3. American College of Cardiology. Preventing Heart Disease. Available at: http://www.acc.org/media/patient/chd/preventing.htm. Accessed June 15, 2005.
4. Summaries for Patients: New definitions for healthy ranges of alanine aminotransferase, a blood test of liver function. Ann Intern Med 2002 Jul 2;137(1):137.
5. de Denus S, Spinler SA, Miller K, Peterson AM. Statins and liver toxicity: a meta-analysis. Pharmacotherapy 2004 May;24(5):584-91.
6. Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis 2004 May;174(1):193-6.
7. Horlander JC, Kwo PY, Cummings OW. Atorvastatin for the treatment of NASH [Abstract]. Gastroenterology 2001;120:A544.
8. Bjerre LM, LeLorier J. Do statins cause cancer? A meta-analysis of large randomized clinical trials. Am J Med 2001 Jun 15;110(9):716-23.
9. Strandberg TE, Pyrorala K, Cook TJ et al. Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet 2004 Aug 28;364(9436):771-7.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
