Can elevated liver enzymes be associated with hypercholesterolemia (high cholesterol)?

From the Guidelines

Elevated liver enzymes can be associated with hypercholesterolemia, as high cholesterol levels can contribute to the development of non-alcoholic fatty liver disease (NAFLD), which is a common cause of elevated liver enzymes. When cholesterol levels are high, particularly LDL (low-density lipoprotein) or "bad" cholesterol, fat can accumulate in the liver, leading to inflammation and damage to liver cells, resulting in the release of liver enzymes such as ALT (alanine aminotransferase) and AST (aspartate aminotransferase) into the bloodstream 1.

Some key factors that contribute to the development of NAFLD and elevated liver enzymes in individuals with hypercholesterolemia include:

• Waist circumference greater than 94 cm for men and 80 cm for women
• Arterial pressure greater than 130/85 mmHg or treated for hypertension
• Fasting glucose greater than 100 mg/dl (5.6 mmol/L) or treated for type 2 diabetes
• Serum triacylglycerols greater than 150 mg/dl (>1.7 mmol/L)
• HDL cholesterol less than 40 mg/dl for men and 50 mg/dl for women (<1.0/<1.3 mmol/L) 2

Lipid-lowering agents such as statins can be considered in patients with NAFLD and dyslipidemia, as they have been shown to decrease liver enzymes and reduce cardiovascular morbidity. In a post-hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study, statin use decreased aminotransferases and poor cardiovascular outcomes in NAFLD patients with aminotransferases up to three times higher than the upper normal limit 1.

It is essential to note that while statins can cause asymptomatic elevation of aminotransferases, this usually appears within 1 year of starting statins and recovers spontaneously. However, the administration of statins to patients with decompensated cirrhosis or acute liver failure should be avoided. If you have elevated liver enzymes and high cholesterol, your doctor might recommend lifestyle changes, including weight loss if needed, regular exercise, limiting alcohol consumption, and following a heart-healthy diet low in saturated fats and refined carbohydrates. These measures can help reduce both cholesterol levels and liver inflammation. Regular monitoring of liver function tests is important when starting cholesterol medications or if you have both conditions.

From the FDA Drug Label

Elevations in Liver Enzyme Tests Persistent elevations in serum transaminases, defined as more than 3 times the ULN and occurring on 2 or more occasions, occurred in 0. 7% of patients who received atorvastatin calcium in clinical trials.

Other adverse reactions reported in placebo-controlled trials include: Metabolic and Nutritional System: transaminases increase, liver function test abnormal, blood alkaline phosphatase increase, creatine phosphokinase increase, hyperglycemia

The FDA drug label does not directly answer whether elevated liver enzymes can be associated with hypercholesterolemia (high cholesterol). However, it does report that elevated liver enzymes were observed in patients treated with atorvastatin calcium, a medication used to treat high cholesterol.

• The label mentions transaminases increase and liver function test abnormal as adverse reactions, but it does not explicitly state that these are associated with hypercholesterolemia.
• It is also noted that hyperglycemia is an adverse reaction, which can be related to metabolic changes, but again, no direct association with hypercholesterolemia is made. 3

From the Research

Association between Elevated Liver Enzymes and Hypercholesterolemia

• Elevated liver enzymes can be associated with various conditions, including non-alcoholic fatty liver disease (NAFLD) 4, 5.
• NAFLD is a common hepatic manifestation of metabolic syndrome, which also includes hypercholesterolemia (high cholesterol) 6.
• Studies have shown that statin use, which is commonly prescribed for hypercholesterolemia, can have a beneficial effect on liver enzymes in patients with NAFLD 4, 5.
• In fact, one study found that statin use was associated with significantly lower levels of ALT, total cholesterol, and LDL in patients with NAFLD 5.

Mechanisms and Relationships

• The pathophysiology of NAFLD includes steatosis, inflammation, and fibrosis, which are exacerbated by dyslipidemia and insulin resistance 6.
• Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, have pleiotropic effects beyond cholesterol-lowering and affect pathways related to inflammation, fibrogenesis, oxidative stress, and microcirculation 6.
• Elevated liver enzymes, such as ALT and AST, can be a marker of liver damage and are often seen in patients with NAFLD and hypercholesterolemia 7, 4.

Clinical Implications

• The use of statins in patients with NAFLD and hypercholesterolemia may have a beneficial effect on both liver enzymes and lipid profile 4, 5.
• However, it is essential to monitor patients on statins and ketogenic diets, as they may be at risk of elevated liver enzymes and hypercholesterolemia 8.
• Further studies are needed to demonstrate the efficacy of statins in liver disease and to understand the relationship between elevated liver enzymes, hypercholesterolemia, and NAFLD 6, 4.