ID22. Aspartate transaminase (AST). (mg/dl, mmol/l) ID24 (U/l)

ID23. Alanine transaminase (ALT). (mg/dl, mmol/l) ID25 (U/l)

Both aspartate transaminase (AST) and alanine transaminase (ALT) are enzymes associated with liver parenchymal cells. The difference is that ALT is found predominantly in the liver, with clinically negligible quantities found in the kidneys, heart, and skeletal muscle, while AST is found in the liver, heart (cardiac muscle), skeletal muscle, kidneys, brain, and red blood cells.

Abnormalities. Disorders or diseases caused or related.

There is a linear relationship between ALT level and body mass index (BMI). A normal ALT level may not exclude significant liver disease.

The degree of elevation of ALT and or AST in the clinical setting helps guide the differentiation. The evaluation of hepatocellular injury includes testing for viral hepatitis A, B, and C, assessment for nonalcoholic fatty liver disease and alcoholic liver disease, screening for hereditary hemochromatosis, autoimmune hepatitis, Wilson’s disease, and alpha-1 antitrypsin deficiency. In addition, a history of prescribed and over-the-counter medicines should be sought. ¹⁷⁴

ALT is a more specific marker of hepatic injury than AST. It is known that AST levels can also be elevated in diseases affecting other organs, such as myocardial infarction, acute pancreatitis, acute hemolytic anemia, severe burns, acute renal disease, musculoskeletal diseases, and trauma.¹⁷²AST increase without elevation in ALT is suggestive of cardiac or muscle disease.

An increase in the activity of aminotransferases (ID24, ID25), especially AST, is observed in myocardial diseases. An increase in the activity of ALT is noted in viral hepatitis A.

Recent studies demonstrated that elevated level ALT activity does not always mean that problem with the liver exists. The overweight and diabetic Asian individuals without hepatic pathologies have higher than an upper threshold level of the activity of ALT (up to 39U/l). It means that such patients should be monitored for subsequent development of detectable NAFLD (nonalcoholic fatty liver disease) as well as nonliver complications, and due diligence should still be exercised by clinicians to exclude common causes for mildly raised ALT such as alcohol and viral hepatitis.

The magnitude of AST and ALT elevation varies depending on the cause of hepatocellular injury. Borderline and mild elevations of AST and/or ALT are seen in a variety of liver-related and non-liver-related conditions as shown in Table ID22.1. Algorithm for evaluation of AST and/or ALT level depending on the magnitude is represented on the figures below table.

Table ID22.1. Causes of elevated AST and ALT

Moderate elevations of AST and/or ALT overlap with the mild and severe lists.

Severe elevations of AST and/or ALT can also come from a variety of sources including

acute viral hepatitis,

ischemic hepatitis/shock liver,

septic shock,

vascular disorders including acute Budd–Chiari syndrome or acute hepatic artery occlusion,

toxin-/medication-induced liver injury,

autoimmune hepatitis,

acute biliary obstruction,

diffuse infiltration of the liver with cancer,

liver trauma/surgery,

venous-occlusive disease/sinusoidal obstruction syndrome,

HELLP syndrome,

Wilson’s disease.

Massive liver-related elevations in AST and/or ALT to >10,000 U/l are generally only seen with shock liver/ischemic hepatopathy, or drug-induced/toxic hepatitis. Also, non-liver-related conditions such as rhabdomyolysis and heatstroke can result in severe to massive AST elevations.

Patients with moderate, severe, and massive elevations of ALT and/or AST require immediate evaluation. Such patients should be evaluated for acute hepatitis including acute hepatitis A, B, C, D, or E, acute reactivation of chronic hepatitis B, and acute hepatitis from non-hepatotropic viruses including herpes simplex, Epstein–Barr virus, or Cytomegalovirus. Acute autoimmune liver disease should also be suspected as well as idiosyncratic drug reactions or direct hepatotoxin exposure (acetaminophen).

The highest levels of aminotransferase elevations are typically seen in those with

acetaminophen overdose,

ischemic hepatopathy,

toxin exposure, such as Amanita phalloides.

History of hematologic malignancy with recent chemotherapy may suggest a diagnosis of sinusoidal obstruction syndrome (venous-occlusive disease).

And, a history of a hypercoagulable state in the setting of abnormal liver tests and ascites should suggest Budd–Chiari syndrome.

Low AST and ALT levels (activity) are generally considered good and are usually not a cause for concern. However, there are some medical conditions and lifestyle factors that can decrease ALT levels.

Vitamin B6 Deficiency

ALT enzyme requires active vitamin B6 to function. Vitamin B6 deficiency is uncommon, but it’s more likely to occur in the elderly, alcoholics (A M Diehl, J Potter et al., 1984), and people with underlying health conditions such as liver, kidney (K Ono, T Ono, T Matsumata, 1995), or inflammatory diseases (Per Magne Ueland, Arve Ulvik, et al., 2015; A M Diehl, J Potter et al., 1984).

Birth Control Pills or Hormone Replacement Therapy (W Ray Kim, Steven L Flamm et al., 2008; Joyce McKenzie, B Miles Fisher et al., 2006)

It was found that ALT levels can decrease in the following cases:

Smoking

Smoking likely lowers ALT in healthy people (Paulo H N Harada et al., 2016; Eun Young Park et al., 2013) but increases it in people with liver disease (Chong-Shan Wang et al., 2002).

Chronic Kidney Disease

ALT decreases in proportion to the progression of the disease. It gets lower as kidney function declines (Sette LH et al., 2015; Ray L. et al., 2015).

Mortality in Senor

Extremely low ALT in the elderly (less than 5 U/L) associates with a higher risk of dying due to existing diseases. (Zhengtao Liu et al., 2014)

Algorithm for evaluation of AST and/or ALT level. HCV, hepatitis C virus

1.        KARMEN, A; WROBLEWSKI, F; LADUE, JS (January 1955). “Transaminase activity in human blood.”. The Journal of clinical investigation 34 (1): 126–31. PMID 13221663Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol 2017;112:18‐35

2.        Giannini, E. G. (1 February 2005). "Liver enzyme alteration: a guide for clinicians". Canadian Medical Association Journal. 172 (3): 367–379. doi:10.1503/cmaj.1040752. ISSN 0820-3946

3.        Gaze DC (2007). "The role of existing and novel cardiac biomarkers for cardioprotection". Current Opinion in Investigational Drugs. 8 (9): 711–7

4.        Daniel Q. Huang, Yee Hui Yeo, et al. ALT Levels for Asians With Metabolic Diseases: A Meta‐analysis of 86 Studies With Individual Patient Data Validation.Hepatol Commun. 2020 Nov; 4(11): 1624–1636. Published online 2020 Sep 9. doi: 10.1002/hep4.1593

5.        Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35. doi: 10.1038/ajg.2016.517. Epub 2016 Dec 20

6.        Lee WM, Stravitz RT, Larson AM. Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology 2012; 55: 965 – 7

7.        Low ALT: Causes & Health Effects. Veronica Tello, PhD (Chemistry) | Last updated: March 2, 2021https://labs.selfdecode.com/blog/low-alt/