Simply Stated: Elevated Enzymes – Quest

Elevated enzymes are a frequently encountered problem in general medical practice, but their meaning often isn’t so simple to discern. When they’re found with a neuromuscular disease, the situation can get complicated.

What’s an enzyme?

There are thousands of enzymes in the cells in our bodies, where they act as catalysts for all the chemical reactions that take place in these cells. Without them, these reactions either wouldn’t occur or would be too slow for the cells’ needs.

Many enzymes are normally present in the blood and can be measured there. When cells are damaged by disease or injury, large amounts of these leak out, causing blood tests to show that enzymes are elevated above normal. (You can roughly compare this situation to a car that’s leaking oil. Leaks in many parts of the engine can have the same result: oil all over your driveway.)

Where did it come from?

Measuring enzymes is only a clue to a possible diagnosis or problem, not a diagnosis in itself. An elevated enzyme level on a screening test should prompt a physician to look further into which areas of the body may be leaking enzymes into the blood, just as a good mechanic looks for the source of a car’s oil leak. (In either case, finding the source is only the first step. The next steps are finding out why the leak has occurred and attempting to fix it.)

Two enzymes often measured on routine tests are known as ALT (alanine transaminase) and AST (aspartate transaminase). ALT is found in the liver, heart, muscles and kidneys. AST is in the liver, heart, muscles, kidneys, brain, pancreas, spleen and lungs. ALT is also known as SGPT (serum glutamic-pyruvic transaminase), and AST is also called SGOT (serum glutamic-oxaloacetic transaminase).

In many neuromuscular disorders, muscle tissue is gradually damaged, either by an attack from the immune system (as in inflammatory myopathies), or by a genetic mutation inside the cells (as in the muscular dystrophies). When routine tests measuring ALT or AST are performed in people with neuromuscular disorders, these enzymes are often elevated in the blood, because the ALT and AST are leaking out of damaged muscles. But they can also leak out of other organs, particularly the liver.

Liver or muscle?

If a neuromuscular disorder hasn’t yet been diagnosed, a doctor may be misled into thinking that a damaged liver, not damaged muscles, is the source of the enzyme leak. In the general population, liver damage is more common than muscle damage, so this assumption isn’t too surprising.

The careful physician will, however, investigate further. An enzyme called GGT or gamma-GT (gamma-glutamyltransferase, also gamma-glutamyltranspeptidase) is found in the liver but not in the muscles. If it’s unclear whether the liver is damaged, a normal GGT level can help a doctor decide that it’s not, while a high GGT level would sway him or her toward thinking it is. (That’s far from the only test that can be done, but it’s an easy and relatively inexpensive one.)

CK (creatine kinase), also called CPK (creatine phosphokinase), is only found in the heart, skeletal muscles and brain. The MM form of CK is the type found in skeletal muscles, and it can be specifically measured when a doctor suspects a muscle problem. A normal CK level with elevated ALT and AST enzymes would sway a doctor toward thinking there’s a liver problem; a high CK with high ALT and AST levels suggests that something’s going on in the muscle.

So, doing additional enzyme tests after a general screen can help a doctor decide whether the high ALT and AST are more likely the result of liver or muscle damage.

Of course, there could be a problem in both liver and muscle. (Your 1982 Volvo could be leaking oil from both the oil pan and a gasket.) Some metabolic muscle disorders, such as acid maltase deficiency and debrancher enzyme deficiency, affect both tissues. And two diseases can occur in the same person.

What damages the liver?

A person at high risk for hepatitis or other liver damage, whether or not he or she has a neuromuscular disease, needs further attention focused on the liver, with the medical history and physical exam taken into account. Liver problems may occur in someone who’s had blood transfusions before 1990 (before modern hepatitis virus testing), taken drugs (prescription, over-the-counter or recreational) that are known to damage the liver, recently eaten potentially contaminated shellfish, had a history of malignancy or recently been stabbed in the abdomen — whether there’s a neuromuscular disease or not.

The medications riluzole, used to treat amyotrophic lateral sclerosis, and methotrexate, used to treat inflammatory myopathies and myasthenia gravis, are among the many drugs that have liver-damaging potential.

Most of the time, elevated ALT and AST levels in people with degenerating muscles don’t mean much, other than that these enzymes, along with CK, are leaking out of the muscles. (The high levels of enzymes do no harm in and of themselves.) But sometimes, depending on results of other tests and the person’s history, they can mean there’s trouble in the liver or even in another organ. That’s where medical detective work is needed.

Serum enzyme levels of CK, LDH, ALT and AST are the most widely measured enzymes in patients suspected of having a muscle disease.  However, it should be noted that the deficiency of a specific enzyme can also be the underlying cause of a muscle disease. For instance, people with metabolic myopathies lack certain enzymes involved in providing energy that help muscles contract. The affected muscles can’t function normally leading to symptoms like progressive muscle weakness, exercise intolerance and even heart problems. Different forms of metabolic myopathies are distinguished by which enzyme is deficient or missing. Examples of diseases associated with reduced levels of specific enzymes include Pompe disease which is caused by acid maltase deficiency; and McArdle disease which is due to a lack of enzyme that assist in carbohydrate metabolism. For more information on enzyme-deficient metabolic myopathies see: (https://www.mda.org/disease/metabolic-myopathies/types)

“Simply Stated” is a Quest column designed to explain some terms and basic facts about neuromuscular diseases.

Disclaimer: No content on this site should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. 

What medications cause liver enzymes to be elevated?

Medically reviewed by Sally Chao, MD. Last updated on March 7, 2022.

Many medications can cause liver enzymes to be elevated.

A familiar over-the-counter medication that can cause liver damage from an overdose is acetaminophen (Tylenol). A healthy person should not take more than 3,000 to 4,000 milligrams in a single day. This maximum dose range may not be safe if you drink alcohol or have liver disease.

Another class of medications that sometimes causes liver enzymes to rise are cholesterol lowering medications, called statins. Statins include the medications simvastatin, atorvastatin, pravastatin and lovastatin. Statins rarely cause liver damage, and doctors no longer check liver enzymes for people on statins routinely.

Other common medications that may cause elevated liver enzymes include:

• The antibiotics synthetic penicillin, ciprofloxacin and tetracycline
• The anti-seizure drugs carbamazepine and phenytoin and valproic acid
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• The diabetes drugs sulfonylureas and glipizide
• The tuberculosis drugs isoniazid, pyrazinamide and rifampin
• The antifungal drug ketoconazole
• The antidepressant fluoxetine
• The antipsychotic risperidone
• The antiviral drugs valacyclovir and ritonavir
• The rheumatoid arthritis drug methotrexate
• Abused drugs such as alcohol, cocaine and anabolic steroids
• The herbal medications chaparral, comfrey tea, kava, skullcap, yohimbe, ji bu huan and ephedra

As part of the Food and Drug Administration (FDA) approval process, medications are screened for their potential to cause liver damage. In most cases, you will not get liver damage if you take these drugs as prescribed. Damage may occur if you are sensitive to the drug, if you take more than prescribed or if you already have a liver condition.

Herbal medications are not tested by the FDA. If you have liver disease, check with your doctor before taking any new medications or supplements.

Liver enzymes

Liver enzymes are proteins your liver uses for normal liver functions. When your liver is damaged, these enzymes leak out into your blood and can be measured with blood testing called liver function testing.

There are several liver enzymes, but the ones that show liver damage from medications are aspartate transaminase (AST) and alanine transaminase (ALT). Medications may cause liver enzymes to be elevated without serious liver damage until they reach 3 to 5 times the normal levels.

References

1. U.S. National Library of Medicine Bookshelf. Liver Function Tests. StatPearls. August 2021. Available at: https://www.ncbi.nlm.nih.gov/books/NBK482489/. [Accessed February 4, 2022].
2. Johnson & Johnson. Tylenol Dosage for Adults. Available at: https://www.tylenol.com/safety-dosing/dosage-for-adults. [Accessed February 9, 2022].
3. U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: Prescription Acetaminophen Products to be Limited to 325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure. February 7, 2018. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-prescription-acetaminophen-products-be-limited-325-mg-dosage-unit. [Accessed February 9, 2022].
4. American College of Gastroenterology (ACG). Medications and the Liver. December 2012. Available at: https://gi.org/topics/medications-and-the-liver/. [Accessed February 4, 2022].
5. Malakouti M, Kataria A, Ali SK, Schenker S. Elevated Liver Enzymes in Asymptomatic Patients — What Should I Do? J Clin Transl Hepatol. 2017 Dec 28;5(4):394-403. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719197/.

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Medical Disclaimer

prices, preparation – Kinzersky Clinic

Description

Professor Kinzersky’s clinic offers blood tests for ALT and AST. Our diagnostic center has a wide range of possibilities for diagnosing diseases. The clinic works according to European standards, the clinic’s specialists use the latest equipment and methods for the effective treatment and diagnosis of diseases. To make an appointment with a physiotherapist, call +7 (351) 200-40-60 or fill out the form on the website.

Preparing for tests

It is recommended to donate blood before a biochemical study on an empty stomach (the last meal should be no earlier than 10-12 hours before). For 2-3 days before the analysis, a sparing diet should be followed. On the eve, you should not drink coffee and strong tea.

In addition, physical activity, stress and medication should be avoided the day before the test.

How to get tested

Procedure duration:

5 minutes

Preparation of results:

1-2 days

Research result:

ALT (alanine aminotransferase) and AST (aspartate aminotransferase) blood test shows the level of these enzymes in the blood. High levels of ALT and AST can indicate damage to cells in the liver, heart, or other organs.

Price of blood test for ALT and AST

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An increase in ALT with HIV/HBV coinfection may indicate NAFLD

According to a study published in Clinical Infectious Diseases, a persistent increase in alanine aminotransferase (ALT) levels in people with HIV and hepatitis B, even despite control of HBV viral load, indicates the need to assess the metabolic risk of developing fatty liver disease (NAFLD).

Using data from a multicentre, prospective cohort study of adults with HIV/HBV coinfection on antiretroviral therapy, we attempted to determine the presence of concomitant fatty liver disease (NAFLD), its activity, and clinical correlates, including cardiovascular disease (CVD) risk. In addition, they evaluated the effect of fatty liver disease on tests (ALT and aspartate aminotransferase [AST]) as an adverse reaction of liver activity over time.

Study participants who were positive for anti-HIV and hepatitis B surface antigen (HBsAg) for at least 6 months were followed up at 8 sites in the Hepatitis B Research Network in the US and Canada. From April 28, 2014 to November 7, 2018, 114 patients underwent liver biopsy. All of them were followed up for an average of 3 years. Steatohepatitis was a consequence of the presence of steatosis, ballooning and perisinusoidal fibrosis. Fatty liver disease (NAFLD) was defined as ≥5% steatosis and/or steatohepatitis.

The mean age of participants was 49 years, 93% were male, 51.3% were black, 92.3% had HIV RNA <400 copies/mL, and 83% had HBV DNA <1000 IU/mL. Of the 114 participants, 11 (9.7%) had steatohepatitis and 23 (20.2%) had steatosis. A higher percentage of participants with at least twice normal ALT levels and abnormal AST levels had fatty liver disease. Half of the participants with steatohepatitis had at least twice the normal ALT (versus 17.4% with steatosis and 7.8% without fatty liver disease), and abnormal AST was observed in 60% of patients with steatohepatitis compared with 30, 4% in patients with steatosis and 15.6% in patients with steatosis without fatty liver disease. NAFLD was more common in patients with a higher degree of inflammation, as measured by the histological activity index, and in patients with a higher degree of perisinusoidal fibrosis; however, there was no significant difference in the Ishak Fibrosis Score between the NAFLD groups.

Compared with participants without fatty liver disease, participants with NAFLD had higher levels of insulin (mean 19 vs 8.5 mcg/mL; P<0.001), glucose (median 94 vs 89 mg/dL; P=0 12), and fatty acid levels (median 0.49 vs. 0.39 mg/dl; P = 0.21).

While traditional lipid profiles, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), did not differ significantly among people with and without fatty liver disease, participants with NAFLD had significantly higher median levels of triglycerides (171 vs. 100.5 mg/dl, P<0.001) and apolipoprotein B (95.5 vs 80.5 mg/dl, P=0.028) compared to the non-NAFLD group. In addition, patients with fatty liver disease had a significantly higher concentration of LDL particles, a low density of LDL-C, and a low concentration of the lower subclass HDL 2-C (P ≤. 001).

After adjusting for age, sex, and alcohol consumption, whites and other races versus blacks (adjusted odds ratio [aOR], 8.49 and 16.54 respectively; P = 0.0004), higher ALT (aOR, 3, 13 per doubling of ALT; P = 0.003), hypertension (aOR, 10.93; P = 0.002), hyperlipidemia (aOR, 4.36; P = 0.04) and family history of diabetes (aOR, 5.38; P = 0.02) were independently associated with higher odds of NAFLD.

After adjusting for HBV DNA, age, and sex, compared with the non-NAFLD group, the presence of steatohepatitis was associated with a 1.93 (95% CI, 1.37–2.72) times increased risk of having ALT levels higher, whereas steatosis without steatohepatitis was associated with a 1.34-fold (95% CI, 1.05–1.70) risk of having ALT abnormal (P<0.001).

Limitations of this study included self-selection of participants seeking liver biopsy, which limited generalization to the entire HIV/HBV population. In addition, although ALT levels were higher in NAFLD in the study cross-section, and this relationship persisted over time when HBV viral levels were controlled, the investigators were unable to determine whether ALT increased at the onset of fatty liver disease.