What are the implications of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hypercholesterolemia, and high high-density lipoprotein (HDL)?

From the Guidelines

Elevated AST, ALT, cholesterol, and HDL levels require immediate medical attention and lifestyle modifications to prevent liver damage and reduce the risk of cardiovascular disease. The most recent and highest quality study, 1, suggests that hepatocellular injury causes the release of ALT and AST in serum, and an increase in ALT is directly linked to hepatocyte injury. The study also notes that common causes of mild increases in aminotransferases are nonalcoholic fatty liver disease (NAFLD) and alcohol-induced liver disease.

To address these issues, the following lifestyle modifications are recommended:

• Adopting a Mediterranean-style diet rich in fruits, vegetables, whole grains, and lean proteins
• Limiting alcohol consumption
• Exercising regularly, aiming for 150 minutes of moderate activity weekly
• Maintaining a healthy weight
• Avoiding medications that may stress your liver

Additionally, medications like statins (such as atorvastatin 10-80mg daily or rosuvastatin 5-40mg daily) may be recommended to lower cholesterol if levels are significantly elevated, as suggested by 1. While elevated HDL (good cholesterol) is generally beneficial, elevated liver enzymes (AST and ALT) may indicate liver inflammation or damage that needs investigation.

It is essential to consult a healthcare provider for proper evaluation and treatment, as they may order additional tests to determine the underlying cause of elevated liver enzymes, which could be related to fatty liver disease, medication side effects, or other conditions requiring specific treatment, as noted in 1.

Key considerations for managing elevated AST, ALT, cholesterol, and HDL levels include:

• Monitoring liver function tests and lipid profiles regularly
• Adjusting medications and lifestyle modifications as needed to prevent liver damage and reduce cardiovascular risk
• Addressing underlying conditions, such as NAFLD or alcohol-induced liver disease, through targeted interventions.

From the FDA Drug Label

Niacin preparations have been associated with abnormal liver tests In three placebo-controlled clinical trials involving titration to final daily niacin extended-release doses ranging from 500 to 3000 mg, 245 patients received niacin extended-release for a mean duration of 17 weeks No patient with normal serum transaminase levels (AST, ALT) at baseline experienced elevations to more than 3 times the upper limit of normal (ULN) during treatment with niacin extended-release. Liver-related tests should be performed on all patients during therapy with niacin extended-release. Serum transaminase levels, including AST and ALT (SGOT and SGPT), should be monitored before treatment begins, every 6 to 12 weeks for the first year, and periodically thereafter (e.g., at approximately 6-month intervals). Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently If the transaminase levels show evidence of progression, particularly if they rise to 3 times ULN and are persistent, or if they are associated with symptoms of nausea, fever, and/or malaise, the drug should be discontinued.

The implications of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are that the patient may be at risk for liver dysfunction.

• Elevated AST and ALT levels should be monitored closely, and if they show evidence of progression or are associated with symptoms, the drug should be discontinued.
• Hypercholesterolemia and high high-density lipoprotein (HDL) are not directly related to the implications of elevated AST and ALT.
• Patients with elevated AST and ALT levels should be carefully evaluated, and liver-related tests should be performed regularly during therapy with niacin extended-release 2.

From the Research

Implications of Elevated AST and ALT

• Elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are associated with liver damage or disease, and can be indicative of nonalcoholic fatty liver disease (NAFLD) 3
• A study found that low LDL-C and high HDL-C levels are associated with elevated serum transaminases, including AST and ALT, amongst adults in the United States 3

Implications of Hypercholesterolemia

• Hypercholesterolemia, or high levels of cholesterol in the blood, is a major risk factor for cardiovascular disease 4, 5
• Elevated levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk of coronary heart disease (CHD) 5
• However, low LDL-C levels can also be associated with elevated liver enzymes, including AST and ALT, due to defects in lipoprotein metabolism or impaired liver synthetic function 3

Implications of High HDL

• High levels of high-density lipoprotein cholesterol (HDL-C) are generally considered desirable, as they are associated with a lower risk of cardiovascular disease 6, 5
• However, a study found that HDL-C levels above 100 mg/dL were associated with higher odds of abnormal liver enzymes, including AST and ALT 3
• The "functionality" of HDL appears more important than the level of HDL-C, and HDL has many cardioprotective effects, including regulating immune function and reverse cholesterol transport 7, 5

Lifestyle and Therapeutic Interventions

• Lifestyle recommendations, including exercise and weight loss, remain first-line therapy in ameliorating insulin resistance and the adverse signaling processes from elevated levels of triglyceride-rich lipoproteins and low HDL-C 7
• Pharmacological agents, such as statins, fibrates, and nicotinic acid, can be used to modify the triglyceride-HDL axis and increase HDL-C levels 4, 5