Alanine Aminotransferase (ALT)

Diagnostic Use

Common causes of raised plasma aminotransferases ALT and AST include

viral hepatitis
alcohol related hepatitis
non-alcoholic fatty liver disease (steatohepatitis)
toxic or ischaemic hepatitis.
Less common causes include

hemochromatosis
autoimmune hepatitis
Wilson’s disease
alpha-1 antitrypsin deficiency.

Patients with cholestatic liver disease, cirrhosis or hepatic carcinoma can have normal or mildly raised aminotransferase activity. Acute biliary obstruction occasionally can cause an early, transient and significant rise in aminotransferase level.

ALT is more liver-specific than AST. ALT is usually increased more than AST in most hepatic conditions. However, AST/ALT >1 can occur in chronic hepatitis, cirrhosis, haemolysis and classically AST is 2 in alcoholic hepatitis.

AST or ALT >3000U/L are rare in viral hepatitis but common in both toxin ingestion (especially acetaminophen) and ischaemia hepatic injury.

When raised aminotransferase is apparently unexplained, several “non-hepatic” conditions may be considered :

Coeliac disease
adrenal glucocorticoid deficiency e.g. Addison’s disease
muscular dystrophies (check CK)
macro-ALT or macro-AST (these are complexes with immunoglobulins, leading to slow clearance of the enzyme; contact laboratory to arrange evaluation)
thyroid dysfunction (hyper or hypo)
sleep apnoea-related disorder (can be associated with or independent of obesity/metabolic syndrome)
Note: The drugs sulfasalazine and sulfapyridine cause negative interference in the assay; patients on these drugs may have falsely low results . Additionally, iron infusions (such as ferric carboxymaltose ) interfere with testing and may give falsely low results or make AST & ALT unmeasurable . This effect appears to resolve rapidly (around 24hrs).

Interpretation

Marked increase (up to 10 – 100x) can occur in acute viral hepatitis, toxic hepatitis or ischaemic/hypoxic liver injury. Occasionally early stage extrahepatic biliary obstruction can induce transient ALT/AST rise.

Other than the above mentioned hepatic conditions, mild to moderate ALT/AST increase can also arise from e.g. cirrhosis, liver tumours, congestive heart failure, autoimmune hepatitis and alcoholic liver disease. Mild isolated increase in ALT is not uncommonly found in patients with fatty liver.

ALT tends to be proportionately higher than AST in inflammatory and infective conditions of the liver, and proportionately lower than AST in conditions such as alcoholic liver disease and cirrhosis.

ALT is generally more specific as a liver pathology test than AST. ALT has a longer half life (around 47hrs) in circulation than AST (half life around 17hrs). Asymptomatic hepatitis carriers usually have normal levels.

Patients with chronic renal failure or on dialysis generally have lower level of ALT and AST activity which may or may not be related to vitamin B6 deficiency. Correspondingly, a lower upper reference limit may have to be applied to interpret ALT or AST level from these patients when these liver enzyme tests are used to monitor occurrence of liver disease.

In patients with raised ALT without an apparent cause, may consider possibility of celiac disease or rarely, Addisons disease.

Reference Intervals