Biomarkers of Liver and Gallbladder Function: ALT

Optimal Takeaways

The alanine aminotransferase (ALT) enzyme is found in metabolically active tissues and facilitates the conversion of amino acids into glucose for energy. It is found primarily in the liver but is also found in the heart, skeletal muscle, and kidneys.

Low ALT may be associated with vitamin B6 insufficiency, frailty, aging, and increased mortality risk from cancer and CVD. Elevations in ALT are often associated with liver and gallbladder pathology. However, mounting evidence suggests they may be related to cardiovascular risk and metabolic disorders, including insulin resistance, metabolic syndrome, obesity, and type 2 diabetes.

Standard Range: 6.00 - 29.00 IU/L

The ODX Range: 10.00 - 26.00 IU/L

Low levels of ALT may be associated with an insufficiency of vitamin B6 (Ramati 2015), decreased muscle mass (Ma 2022), aging and frailty (Liu 2014), and CVD and cancer mortality in the elderly (Ke 2022).

High levels of ALT may be associated with alcohol ingestion, hepatic necrosis, ischemia, or tumor, hepatitis, cirrhosis, cholestasis, obstructive jaundice, muscle inflammation or damage, pancreatitis, MI, severe burns, shock, and infectious mononucleosis (Epstein-Barr viral infection). Drugs that can increase ALT include allopurinol, antibiotics, carbamazepine, clofibrate, oral contraceptives, phenytoin, salicylates, and verapamil (Pagana 2021). Acetaminophen may increase ALT even at commonly used doses (Heard 2010).

Levels can also be elevated with increased alcohol intake, hemochromatosis, vascular disease, celiac disease, excessive exercise (Moriles 2021), obesity, metabolic syndrome, insulin resistance, diabetes (Liu 2014), cardiovascular disease, and inflammation (Shen 2015). Levels may be significantly elevated with common bile duct stones, ischemic or viral hepatitis, medications, and liver cancer (Bjornsson 2016).

Overview

Alanine aminotransferase (ALT), previously known as SGPT, is an enzyme that participates in gluconeogenesis. It facilitates the transfer of amino groups from alanine to alpha-ketoglutarate to produce glutamate as well as pyruvate, which can then be converted to energy via the Krebs cycle, a vitamin B6-dependent process. Common causes of elevated ALT include alcohol ingestion, NAFLD, NASH, hepatitis, drug/herbal-induced liver injury, hemochromatosis, vascular disease, celiac disease, Wilson disease, and genetic factors. Diurnal rhythms are observed with ALT, with levels at their lowest at 4 am and highest at 4 pm. Medications that can increase ALT include statins, phenytoin, allopurinol, and antibiotics, especially amoxicillin. However, more than 50% of drug-induced liver injuries come from acetaminophen (Moriles 2021). Acetaminophen can cause significant elevations in ALT levels even in those with minimal alcohol intake, increasing median ALT from 24 IU/L to 39 IU/L with a dose of 4,000 mg/day, previously considered a common dose (Heard 2010).

ALT is found predominantly in the liver, and elevations often are related to the liver. A prospective study of 155 adults with an ALT of 500 IU/L or higher found the most common causes for these extreme levels were common bile duct gallstone, ischemic hepatitis, viral hepatitis, drug-induced liver injury (DILI), and hepatobiliary malignancy (Bjornsson 2016).

However, ALT is also found in the heart, skeletal muscle, and kidneys; serum changes can reflect dysfunction in these tissues (Pagana 2021). Mild to moderate increases in serum ALT can be associated with metabolic disorders, including obesity, hyperlipidemia, metabolic syndrome, insulin resistance, and type 2 diabetes. In general, levels may be higher in males than females. Interestingly, moderate alcohol and coffee intake may protect against ALT elevations (Liu 2014).

Increased ALT is often attributed to dysfunctional glucose metabolism and NAFLD. However, researchers suggest it may also reflect endothelial dysfunction, atherosclerosis, inflammation, and CVD risk. In one study of 610 individuals being worked up for chest pain, the mean ALT was significantly higher at 42.3 IU/L in those diagnosed with CAD versus 18.3 IU/L in those without CAD (Shen 2015).

A reduction in the upper end of the conventional lab range may be indicated to identify many of these pathological conditions. A retrospective study of 3,769 Chinese subjects led researchers to reduce the upper cut-off values for ALT from 40 IU/L to 22.15 IU/L for healthy men and 22.40 IU/L for healthy women. Higher levels were associated with higher BMI, alcohol intake, serum cholesterol, and triglycerides (Zhang 2015). Other researchers call for an update to the conventional range as well. Those reviewing NHANES data comprising 18,518 participants recommend an upper cut-off for ALT of 29 IU/L in men and 22 IU/L in women to discriminate between those with hepatitis C and those with a lower risk of liver disease (Ruhl 2012).

Note the predominance of ALT versus AST elevation in various conditions (Kasarala 2016).

ALT predominant

• Chronic hepatitis B, C
• Acute viral hepatitis (types A‐E, herpes simplex virus, Epstein‐Barr virus, cytomegalovirus)
• Steatosis /steatohepatitis
• Hemochromatosis
• Medications/toxins
• Autoimmune hepatitis
• Wilson's disease
• Celiac disease

AST predominant:

• • Alcohol‐related liver injury
  • Cirrhosis
  • Hemolysis
  • Myopathy
  • Thyroid disease
  • Strenuous exercise

References

Bjornsson, Helgi Kristinn et al. “A prospective study on the causes of notably raised alanine aminotransferase (ALT).” Scandinavian journal of gastroenterology vol. 51,5 (2016): 594-600. doi: 10.3109/00365521.2015.1121516

Heard, Kennon J et al. “Serum alanine aminotransferase elevation during 10 days of acetaminophen use in nondrinkers.” Pharmacotherapy vol. 30,8 (2010): 818-22. doi:10.1592/phco.30.8.818

Kasarala, George, and Hans L Tillmann. “Standard liver tests.” Clinical liver disease vol. 8,1 13-18. 26 Jul. 2016, doi:10.1002/cld.562

Ke, Pan et al. “Association of the serum transaminase with mortality among the US elderly population.” Journal of gastroenterology and hepatology, 10.1111/jgh.15815. 1 Mar. 2022, doi:10.1111/jgh.15815

Lala, Vasimahmed, et al. “Liver Function Tests.” StatPearls, StatPearls Publishing, 20 August 2021

Liu Z, Que S, Xu J, Peng T. Alanine aminotransferase-old biomarker and new concept: a review. Int J Med Sci. 2014 Jun 26;11(9):925-35.

Ma, Wenjie et al. “Association between ALT/AST and Muscle Mass in Patients with Type 2 Diabetes Mellitus.” Mediators of inflammation vol. 2022 9480228. 14 Oct. 2022, doi:10.1155/2022/9480228

Moriles, Kevin E. and Samy A. Azer. “Alanine Amino Transferase.” StatPearls, StatPearls Publishing, 9 May 2021.

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Ramati, Erez, et al. "Low ALT activity amongst patients hospitalized in internal medicine wards is a widespread phenomenon associated with low vitamin B6 levels in their blood." Harefuah 154.2 (2015): 89-93.

Ruhl, Constance E, and James E Everhart. “Upper limits of normal for alanine aminotransferase activity in the United States population.” Hepatology (Baltimore, Md.) vol. 55,2 (2012): 447-54. doi:10.1002/hep.24725

Shen, Jianying et al. “Correlation of serum alanine aminotransferase and aspartate aminotransferase with coronary heart disease.” International journal of clinical and experimental medicine vol. 8,3 4399-404. 15 Mar. 2015

Zhang, Peng et al. “Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese.” World journal of gastroenterology vol. 21,8 (2015): 2419-24. doi:10.3748/wjg.v21.i8.2419