How Much Do Statins Raise Liver Enzymes?

Statins can be continued in patients with transaminase levels no more than three times the upper limit of normal, often resolving spontaneously. They have also been associated with hepatitis, which is signaled by elevations in alanineaminotransferase and aspartate aminotransferase levels. Hepatotoxicity by statins is usually defined as an increase in alanine aminotransferase (ALT) to 2-3 times higher than the upper normal limit or more than a twofold increase in conjugated bilirubin.

Clinical trials have shown that statin use has been associated with elevations in serum alanine aminotransferase (ALT) levels in approximately 3 of persons who take statins. However, individuals with elevated baseline liver enzymes do not have a higher risk for hepatotoxicity from statins. Statins have been contraindicated in patients with active liver disease and persistent elevated transaminase levels.

Liver damage can occur if statin use causes an increase in enzymes in the liver, signaling inflammation. If the level remains stable, continue as normal. If ALT is greater than 3 times the upper limit of normal, reduce the statin dose and repeat ALT in 4-6 weeks. “Statin-induced hepatotoxicity is a myth”, wrote a Lancet author. About 10 of patients see liver enzymes rise after starting a statin, which can cause liver damage.

How often should I check my LFTs on statins?

The ATP III guidelines for monitoring statin therapy include checking lipid panels at baseline, 6-8 weeks after starting or adjusting the medication/dose, and every 4-6 months. LFTs should be checked at baseline, approximately 12 weeks after starting therapy, then annually or more frequently if indicated. Creatine kinase (CK) should be checked at baseline and if the patient reports muscle soreness, tenderness, or pain. A Liver Expert Panel evaluated the liver-associated risks of statins, reporting that routine monitoring could potentially identify patients with isolated increased transaminase levels, potentially leading to unnecessary discontinuation of statin therapy.

In 2006, the National Lipid Association (NLA) Statin Safety Taskforce published recommendations stating that LFTs should be monitored before initiation of treatment and when clinically indicated. The ATP III and NLA consider a critical elevation to be an ALT or AST greater than three times the ULN and both recommend rechecking to confirm the elevation. Once confirmed, the NLA recommends clinical judgment to decide whether to continue, reduce the dose, or discontinue treatment.

In 2012, the FDA released updated recommendations for the monitoring of LFTs, resulting in revisions of all statin labels. The FDA concluded that serious liver injury with statins is rare and unpredictable in individual patients, and routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.

How long after stopping statins do liver enzymes return to normal?

Abstract. Atorvastatin has been associated with liver injury. We reported here two cases of aminotransferases elevation within 12 h of low-dose atorvastatin therapy. Liver functions were fully recovered to the baseline level 11 days after discontinuation of atorvastatin treatment. The possible relative risk factors included advanced age, chronic and systemic diseases, and co-administration of cytochrome P450 3A (CYP3A) enzyme-dependent metabolic drugs or its inhibitors such as clopidogrel and diltiazem. No significant transaminase elevation was observed after switching to pravastatin. Thus, pravastatin might be safer than atorvastain in patients with chronic or systemic diseases, or with co-administration of CYP3A enzyme-dependent drugs.

Keywords: atorvastatin, pravastatin, liver injury, cytochrome P450 3A enzyme.

Introduction. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) are safe to the treatment of hyperlipidemia and prevention of coronary artery diseases. Few common side effects of statins include myopathy, gastrointestinal disturbance, depression, and liver injury. According to Motola et al. , the rate of statin-associated hepatic reactions is 10. 9% in a total of 1, 254 adverse drug reaction reports from January 1990 to May 2005. Statins are among those with the highest rate of hepatic reactions, higher than antiplatelet agents and non-steroidal anti-inflammatory drugs. Various hepatotoxic side effects related to atorvastatin therapy have been reported ( 2, 3 ), raising a potential concern of atorvastatin-associated liver injury in Chinese populations. Here we report two patients who demonstrated significant elevation of serum alanine amino-transferase (ALT) levels immediately after atorvastatin therapy, but without cross-toxicity to the livers after switching to pravastatin.

How long does it take for statins to affect the liver?

Statin-associated hepatocellular injury, a common side effect of statin use, occurs 5 to 90 days after therapy initiation. Severe hepatocellular liver injury, with a mortality rate of 10 and an incidence of 0. 7-1. 3 per 100, 000 cases of drug-induced liver injury (DILI), is rare and typically reversible without intervention. Statins, which work by competitively inhibiting HMG-CoA reductase, the rate limiting enzyme of the cholesterol synthetic pathway, have gained widespread acceptance due to their lipid lowering activity, which helps prevent the development of atherosclerosis. They are most commonly used in the treatment of hypercholesterolemia and dyslipidemia for primary reduction cardiovascular disease and secondary risk reduction in patients with pre-existing coronary artery disease-related events.

Statins have been approved for cholesterol lowering in the US since their introduction in 1987, with seven other statins (atorvastatin, fluvastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) receiving Federal Drug Administration approval. Cerivastatin was withdrawn in 2001 due to a high risk of rhabdomyolysis. Current literature supports statin-induced liver injury presenting in either hepatocellular or cholestatic patterns, with the former being the prevailing pattern of injury.

When to check LFT after statin?

Before starting to take statins, you should have a blood test to check how well your liver and kidneys are working. You should also have a routine blood test to check the health of your liver 3 months after treatment begins, and again after 12 months.

Pregnancy and breastfeeding. Statins should not be taken by anyone who is pregnant or breastfeeding, as there’s no firm evidence on whether it’s safe to do so.

Contact a GP for advice if you become pregnant while taking statins.

What if ALT is 3 times upper limit of normal statin?

If ALT is raised but less than 3 times the upper limit of normal, repeat ALT in 4-6 weeks. If the level remains stable, continue as normal. If ALT is greater than 3 times the upper limit of normal, reduce the statin dose and repeat ALT in 4-6 weeks.

How common is liver failure with statins?

Liver dysfunction caused by statins is a common clinical issue, with an incidence of 1. 9 to 5. 5. The types of liver dysfunction caused by different statins vary, with most liver injury caused by simvastatin being hepatocellular liver injury. A meta-analysis found that atorvastatin showed a higher risk of transaminase elevations than non-statin control, pravastatin, and simvastatin. Hepatocellular, cholestasis, and autoimmune hepatitis may appear infrequently months to years after initiation of statins.

There are countermeasures to statin-induced liver dysfunction, such as using an appropriate combination of liver protectants and rechecking liver function weekly until normal. Restarting low-dose statin therapy or switching to other statins is encouraged for patients at high and very high risk of ASCVD. However, prospective monitoring of statin-induced liver injury is not justified unless the patient would otherwise benefit from such monitoring.

The lowest effective dose of statins should be recommended, and the combination with CYP3A4 inhibitors or other drugs that may aggravate liver damage should be avoided. Patients who used both vitamin K antagonists and statins had a lower risk of adverse drug reactions (ADR) compared to concomitant treatment with non-vitamin K antagonist oral anticoagulants and statins. A history of liver and biliary diseases should be checked before using statins, and differential diagnosis and treatment should be performed if liver transaminase is elevated.

How common is liver damage from statins?

Liver dysfunction caused by statins is a common clinical issue, with an incidence of 1. 9 to 5. 5. The types of liver dysfunction caused by different statins vary, with most liver injury caused by simvastatin being hepatocellular liver injury. A meta-analysis found that atorvastatin showed a higher risk of transaminase elevations than non-statin control, pravastatin, and simvastatin. Hepatocellular, cholestasis, and autoimmune hepatitis may appear infrequently months to years after initiation of statins.

There are countermeasures to statin-induced liver dysfunction, such as using an appropriate combination of liver protectants and rechecking liver function weekly until normal. Restarting low-dose statin therapy or switching to other statins is encouraged for patients at high and very high risk of ASCVD. However, prospective monitoring of statin-induced liver injury is not justified unless the patient would otherwise benefit from such monitoring.

The lowest effective dose of statins should be recommended, and the combination with CYP3A4 inhibitors or other drugs that may aggravate liver damage should be avoided. Patients who used both vitamin K antagonists and statins had a lower risk of adverse drug reactions (ADR) compared to concomitant treatment with non-vitamin K antagonist oral anticoagulants and statins. A history of liver and biliary diseases should be checked before using statins, and differential diagnosis and treatment should be performed if liver transaminase is elevated.

How high do statins raise liver enzymes?

Statins, a type of cholesterol-lowering medication, act in the liver by inhibiting HMG-CoA reductase, which temporarily depletes intracellular cholesterol and induces the production of LDL receptors. These effects can range from mild transaminase elevation to very rare hepatotoxicity with severe liver injury. In about 1 of patients, statins cause asymptomatic and dose-related elevations in transaminases greater than 3 times the upper limit of normal, which does not indicate hepatocellular injury or liver synthetic dysfunction.

Clinicians should obtain baseline liver function studies prior to statin initiation to identify individuals with pre-existing dysfunction who may be at theoretical risk of drug-related injury. It is not currently possible to predict which patients will develop hepatotoxicity, and providers must be alert to symptoms and signs of this rare complication.

Epidemiologic studies have found an inverse relationship between cholesterol levels and the risk of hemorrhagic stroke, but the available aggregate data shows no such increased risk in a primary prevention population. Fall risks may be increased in secondary stroke prevention, but the absolute risk appears small relative to the benefit of overall stroke and vascular event rate reduction.

An association between the development of peripheral neuropathy and statin use is noted in observational studies, but large epidemiologic studies are inconsistent and randomized controlled trials support no causal relationship.

Will 10mg of atorvastatin damage the liver?

Common side effects include muscle cramps, headache, joint aches, abdominal pain, nausea, and weakness, symptoms that occur with all of the currently available statins. Rare but potentially severe adverse events include liver injury, myopathy, rhabdomyolysis, and immune-mediated necrotizing myopathy.

Abbreviations used: ANA, antinuclear antibody; HDL, high density lipoprotein; LDL, low density lipoprotein; OD, odds ratio.

Zimmerman HJ. Drugs used in the treatment of hypercholesterolemia and hyperlipidemia. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 660-2.

(Expert review of hepatotoxicity published in 1999; the statins have dose related hepatic effects in guinea pigs and rabbits and transient elevations in aminotransferases occur in 1-5% of humans treated; several cases of clinically apparent liver injury from lovastatin and simvastatin have been published).

At what ALT level should statins be stopped?

Liver enzymes should be monitored in all patients who take statins. If the alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level doubles, the statin should be stopped. Elevation in liver enzymes with statin therapy is dose- related.

How do you know if statins are damaging your liver?

Statins can also cause liver damage, so doctors should test liver function before starting a patient on statins, and test liver function afterwards only if the patient is displaying symptoms of liver failure. These symptoms include: jaundice (the skin becomes yellowish), bleeding easily, and a swollen belly.

Statins are the most popular type of cholesterol-lowering medication and among the most widely prescribed drugs in the world. Popular brands include Lipitor, Zocor, Crestor and Vytorin. They prevent the body from making cholesterol and can help prevent heart disease and stroke. While these medications can substantially lower your cholesterol, the benefits do not outweigh the risks for everyone who has high cholesterol.

The greatest risks of statins are muscle pain, memory loss, forgetfulness, confusion, and high blood sugar levels that can result in Type 2 diabetes.

Several studies have found that people who take statins, especially at high dosages, are more likely to develop diabetes. This was first noticed when a clinical trial showed an unexpected 27% increase in new cases of diabetes among patients taking Crestor, compared with patients who took placebos. ( 1) An analysis in 2011 of five clinical trial studies found a link between the onset of diabetes and the use of high-dose statins (80 mg), compared to moderate doses of the same pills (40 mg, 20 mg, or 10 mg, depending on the study). In all five studies, patients who had suffered acute coronary syndrome (ACS) and patients who have stable coronary heart disease were more likely to develop diabetes if they were taking higher doses of statins. Acute coronary syndrome is a medical term that includes any symptoms of an insufficient blood supply to the heart muscle. In addition, a study of women who were over 55 reported that taking a statin increased the risk of a new diagnosis of diabetes.