What Level Of Ggt Is Dangerous

What Level Of Ggt Is Dangerous

Gamma-glutamyl Transferase (GGT) Test

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Gamma-glutamyl transferase: risk and prognosis of cancer

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.

PMCID: PMC3341856 PMID: 22531718

Gamma-glutamyl transferase (GGT) is a membrane-bound enzyme catabolising reduced glutathione to cysteine and glycine in Meister’s γ-glutamyl cycle (Orlowski and Meister, 1970). This delivers cysteine for intracellular synthesis of glutathione, the major thiol anti-oxidant. Elevated serum levels of GGT are markers of oxidative stress, resulting from factors including alcohol, heavy metals, cardiovascular disease and diabetes.

In this issue, an Austrian multicentre study is reported, which shows an association between GGT and prognosis in women with endometrial carcinoma (Seebacher et al, 2012). Gamma-glutamyl transferase levels were evaluated in 874 consecutive patients who were stratified in risk groups. After multivariate analysis, elevated and highly elevated serum GGT levels were independently associated with poorer survival. There was no association with advanced tumour stage, higher tumour grade or with more aggressive histology.

High levels of GGT seem to increase the risk of progression of high-grade cervical dysplasia to invasive carcinoma. Recently, as part of a multi-centre trial, pre-treatment GGT levels were examined in 692 patients with cervical cancer (Polterauer et al, 2011). Gamma-glutamyl transferase serum levels were significantly associated with FIGO stage and age (but not with lymph node involvement (P=0.85), and histological type. There was a linear correlation between GGT and prognosis.

Furthermore, higher serum levels of GGT, within the normal range, are associated with an increased cancer risk. In the Vorarlberg study of 92 983 females, there was an increasing hazard rate for various cancers with higher levels of the enzyme (Strasak et al, 2008). Within the Guernsey Cohort Study, a highly significant association was found between levels of GGT and breast cancer risk in premenopausal women (Fentiman and Allen, 2010). These results were confirmed in the Apolipoprotein Mortality Risk (AMORIS) study of 545 460 Swedes (Van Hemelrijck et al, 2011). When subdivided by categories of GGT (72 U l –1 ) there was an increasing association with overall cancer risk. For those with glucose levels >6.11 mmol l –1 , the association with risk of prostate, breast and liver cancer became stronger, supporting a role for oxidative stress in the process of carcinogenesis.

In the third US National Health and Nutrition Examination Survey (NHANES) blood lead and urinary cadmium levels were measured together with serum GGT in 10 098 adults (Lee et al, 2006). After adjustment for race, sex and age, both blood lead and urinary cadmium levels showed graded positive associations, with serum GGT. Subsequently, elevated urinary cadmium levels were shown to be associated with increased breast cancer risk (Gallagher et al, 2010). This strong association with a marker of oxidative stress in a normal population suggests a possible carcinogenic role for lead and cadmium in individuals with low environmental exposure.

Death certificate-based 12-year mortality was also examined in the third NHANES project in relation to serum alanine amino-transaminase (ALT) and GGT (Ruhl and Everhart, 2009). Elevated ALT was associated with deaths from hepatic disease but not with all-cause mortality. In contrast, elevated GGT was associated with all-cause mortality from liver disease, neoplasms and diabetes.

There is evidence that GGT is dysregulated in malignant cells and by producing reactive oxygen species cause tumour progression towards more aggressive phenotypes associated with a worse prognosis (Dawson et al, 1979, Hanigan et al, 1999). In a study of human GGT-transfected melanoma cells, higher levels of GGT activity were associated with greater levels of background DNA damage and oxidised bases (Corti et al, 2008). This was unrelated to differences in cell cycle distribution or apoptotic rates. Culture of GGT-over-expressing cells with GGT substrates and catalytic iron resulted in further DNA damage, eliminated in the presence of GGT inhibitors such as L-2-amino-4-boronobutanoic acid (ABBA).

Curcumin, a polyphenol extracted from Curcuma longa has anti-tumour effects on ZR-75-1 cells, resistant to oxidative damage (Quiroga et al, 2010). In a dose-dependent manner, it is both cytotoxic and inhibitory to GGT activity. If elevated levels of GGT are marking an increased risk of recurrence of cancer, it is possible that curcumin has therapeutic potential in this situation. Under other circumstances the agent has been shown to be both effective and non-toxic in a randomised double-blind placebo-controlled trial of Iranian war veterans with sulphur mustard-induced pruritus (Panahi et al, 2011).

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So, what can be made of this? In terms of carcinogenesis, GGT clearly is a marker of oxidative stress. What is unclear is whether GGT has a direct aetiological role or is an indicator of collateral damage. Another factor to be considered is that GGT is elevated by alcohol consumption, which has a direct role in carcinogenesis for liver, pancreas, larynx and breast. It should, however, be noted that higher levels of GGT within the normal range are associated with increased risk of cancer so that causes other than alcohol may be involved. More basic studies are needed using mice with GGT knockout to determine whether GGT has an aetiological role in carcinogenesis or is a mere marker of damage. In patients who have been treated for cancer, higher levels of GGT may signal ongoing oxidative stress. The role of non-specific inhibitors of GGT such as curcumin is potentially interesting but what we need is a specific non-toxic GGT inhibitor that can be tested in a wider preventive/adjuvant role in selected patients with premalignant changes or established cancer.

References

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Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

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Gamma-glutamyl Transferase (GGT) Test

A gamma-glutamyl transferase (GGT) test measures the amount of GGT in your blood GGT is an enzyme. Enzymes are proteins that speed up certain chemical reactions in your body. Thousands of enzymes play an important role in all of your body functions. The GGT enzyme is found throughout your body, but it is mainly found in your liver.

If your liver or bile duct is damaged, GGT may leak into your bloodstream. So high levels of GGT in your blood may be a sign of liver disease or damage to the bile ducts. Bile ducts are tubes that carry bile in and out of the liver. Bile is a fluid made by the liver that is important for digestion.

A GGT test can’t diagnose the specific cause of liver disease. The test can only indicate that your liver is being damaged. This test is usually done with or after other liver function tests, most often an alkaline phosphatase (ALP) test. ALP is another type of liver enzyme. While both your GGT and ALP may be elevated in diseases that affect your bile ducts and liver, only ALP will be elevated in bone disease. This helps your health care provider to understand if your issue may be due to a bone disorder instead of your liver.

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Other names: gamma-glutamyl transpeptidase, GGTP, Gamma-GT, GTP

What is it used for?

A GGT test is most often used to:

  • Help diagnose liver disease
  • Figure out if liver damage is due to liver disease or a bone disorder
  • Check for blockages in the bile ducts
  • Screen for or monitor alcohol use disorder (AUD). Drinking alcohol increases GGT levels. Most people with AUD have high GGT levels.

Why do I need a GGT test?

You may need a GGT test if you have symptoms of liver disease. They may include:

  • Fatigue
  • Weakness
  • Jaundice, a condition that causes your skin and eyes to turn yellow
  • Loss of appetite
  • Abdominal (belly) pain or swelling
  • Nausea and vomiting
  • Severe itching

Your provider may use this test to monitor your alcohol use if you’re being treated for AUD. You may also need this test if you have abnormal results on an ALP test and/or other liver function tests.

What happens during a GGT test?

A health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.

Will I need to do anything to prepare for the test?

Talk to your provider to see if there are any specific instructions, since. the results of your GGT test may be affected by:

  • Certain medicines or supplements
  • Drinking alcohol
  • Smoking cigarettes

GGT levels go down after meals. Your provider may also ask you to fast for a certain amount of time before testing.

Are there any risks to a GGT test?

There is very little risk to having a blood test. You may have slight pain or bruising at the spot where the needle was put in, but most symptoms go away quickly.

What do the results mean?

If your results show higher-than-normal levels of GGT, it may be a sign of liver damage. The damage may be due to one of the following conditions:

  • Hepatitis.
  • Cirrhosis.
  • Alcohol use disorder (AUD).
  • Pancreatitis.
  • Diabetes.
  • Heart failure.
  • Side effects of a medicine. Certain medicines can cause liver damage in some people.

The results can’t tell you which condition is causing your liver damage, but they can help show how much damage there is. Usually, the higher the level of GGT, the more liver damage you have.

If your results show low or normal levels of GGT, you probably don’t have liver disease.

Your results may also be compared with the results of an ALP test. ALP tests help diagnose bone disorders. Together, your results may show one of the following:

  • High levels of ALP and high levels of GGT mean your symptoms are likely due to a liver disorder and not a bone disorder.
  • High levels of ALP and low or normal GGT levels mean it’s more likely you have a bone disorder.

If you have questions about your results, talk to your provider. Your provider will consider your symptoms, medical history, and the results of other blood tests to understand the results of your GGT test.

Is there anything else I need to know about a GGT test?

In addition to an ALP test, your provider may order liver function tests with or after the GGT test. These may include:

  • Alanine aminotransferase, or ALT
  • Aspartate aminotransferase, or AST
  • Lactic dehydrogenase, or LDH

References

  1. American Liver Foundation. [Internet]. New York: American Liver Foundation; c2024. Diagnosing Liver Disease – Liver Biopsy and Liver Function Tests; [updated 2024 Jan 12; cited 2024 Feb 28]; [about 7 screens]. Available from: https://liverfoundation.org/for-patients/about-the-liver/diagnosing-liver-disease/#1503683241165-6d0a5a72-83a9
  2. Cleveland Clinic: Health Library: Diagnostics and Testing [Internet]. Cleveland (OH): Cleveland Clinic; c2024. Blood Tests; [reviewed 2022 Dec 06; cited 2024 Feb 28]; [about 16 screens]. Available from: https://my.clevelandclinic.org/health/diagnostics/24508-blood-tests
  3. Cleveland Clinic: Health Library: Diagnostics and Testing [Internet]. Cleveland (OH): Cleveland Clinic; c2024. Gamma-Glutamyl Transferase (GGT) Test; [reviewed 2021 Nov 09; cited 2024 Mar 18]; [about 11 screens]. Available from: https://my.clevelandclinic.org/health/diagnostics/22055-gamma-glutamyl-transferase-ggt-test
  4. Hinkle J, Cheever K. Brunner and Suddarth’s Handbook of Laboratory and Diagnostic Tests. 2nd Ed, Kindle. Philadelphia: Wolters Kluwer Health, Lippincott Williams and Wilkins; c2014. Gamma Glutamyl Transferase; p. 314.
  5. Kunutsor SK. Gamma-glutamyltransferase-friend or foe within? Liver Int. 2016 Dec;36(12) [cited 2024 Mar 18]. [about 18 screens].:1723-1734. doi: 10.1111/liv.13221. Epub 2016 Aug 31. PMID: 27512925.
  6. Labcorp [Internet]. Burlington (NC): Laboratory Corporation of America(r) Holdings; c2023. Patient Test Information: γ-Glutamyl Transferase (GGT); [cited 2024 Mar 18]; [about 5 screens]. Available from: https://www.labcorp.com/tests/001958/glutamyl-transferase-ggt
  7. Mayo Clinic Laboratories [Internet]. Mayo Foundation for Medical Education and Research; c1995-2024. Test ID: GGT: Gamma-Glutamyltransferase, Serum: Clinical and Interpretive; [cited 2024 Feb 283]; [about 4 screens]. Available from: https://www.mayocliniclabs.com/test-catalog/overview/8677#Clinical-and-Interpretive
  8. Nemours KidsHealth [Internet]. Jacksonville (FL): The Nemours Foundation; c1995-2024. Getting a Blood Test; [reviewed 2021 Sep; cited 2024 Feb 28]; [about 4 screens]. Available from: https://kidshealth.org/en/parents/blood-tests.html
  9. Nemours KidsHealth [Internet]. Jacksonville (FL): The Nemours Foundation; c1995-2024.Blood Test: Gamma-Glutamyl Transpeptidase (GGT); [reviewed 2022 Nov; cited 2024 Mar 18]; [about 2 screens]. Available from: https://kidshealth.org/en/parents/test-ggt.html
  10. Pathology Tests Explained [Internet]. Alexandria (Australia): Australasian Association for Clinical Biochemistry and Laboratory Medicine; c2023. Gamma glutamyltransferase (GGT); [reviewed 2023 June 23; cited 2024 Mar 18]; [about 3 screens]. Available from: https://pathologytestsexplained.org.au/ptests-pro.php?q=Gamma%20glutamyltransferase%20(GGT)
  11. Testing.com [Internet]. Seattle (WA): OneCare Media; c2024. GGT Blood Test (Gamma-Glutamyl Transferase/Transpeptidase); [updated 2022 Sep 29; cited 2024 Feb 28]; [about 9 screens]. Available from: https://www.testing.com/tests/gamma-glutamyl-transferase-ggt/
  12. Xing M, Gao M, Li J, Han P, Mei L, Zhao L. Characteristics of peripheral blood Gamma-glutamyl transferase in different liver diseases. Medicine (Baltimore). 2022 Jan 7;[cited 2024 Mar 18] [about 17 screens]. 101(1):e28443. doi: 10.1097/MD.0000000000028443. PMID: 35029891; PMCID: PMC8735790.

Related Health Topics

  • Alcohol Use Disorder (AUD)
  • Bile Duct Diseases
  • Bone Diseases
  • Cirrhosis
  • Hepatitis
  • Jaundice
  • Liver Diseases
Dr Narelle Bleasel FACD
Dr Narelle Bleasel FACD

Dermatologist in Battery Point, Australia

Articles: 523

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