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Liver function tests (LFTs)

Article · March 2010

DOI: 10.1177/201010581001900113

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Laboratory Insights

Liver Function Tests (LFTs)

Clementine YF Yap, MSc, DLM(ASCP), Tar Choon Aw, FRCP (Edin), FRCPA
Department of Lab Medicine, Changi General Hospital, Singapore

Abstract

Each liver function test by itself is neither highly sensitive nor specific but when interpreted together may provide
the clinician with useful information about the patient’s liver, and may also indicate other health issues such as
malnutrition and bone disease.

Keywords: albumin, ALP, ALT, AST, bilirubin, hepatocellular injury, liver function tests

Synonyms liver and non-liver diseases. Liver disease may be

Liver Panel, Liver Injury Tests, Liver Profile broadly categorised into 4 groups: inflammatory,
vascular, metabolic and neoplastic disorders. Viral
Tests Commonly Included infection, hepato-toxic drugs and alcohol abuse
Liver function tests (LFTs) include alanine cause hepatitis and hepatocyte injury, and hence
aminotransferase (ALT), alkaline phosphatase liver inflammation. Chronic liver inflammation
(ALP), aspartate aminotransferase (AST), bilirubin (e.g. hepatitis viruses or haemochromatosis) often
and albumin. leads to cirrhosis; a condition characterised by
irreversible liver scarring and fibrosis, and increased
Specimen risk for liver cancer. Metabolic disorders that affect
Serum is the specimen of choice. Blood may the liver include the hereditary alpha-1 antitrypsin
be collected in serum separator tubes with or deficiency, Wilson’s disease and haemochromatosis.
without additives. Cancers in the liver may arise de novo in the
liver, progress from cirrhosis or spread from
All specimens should be handled with standard cancers elsewhere.
precautions and sent to the lab immediately for
processing. Specimens that cannot be analysed ALT and AST
immediately should be centrifuged, serum ALT and AST are sensitive indicators of hepatocellular
refrigerated and analysed as soon as possible. injury but they lack specificity as they are also
present in muscle (cardiac and skeletal), kidney,
Indications and RBCs. In hepatocyte cytoplasm AST is more
As the liver is involved in excretory, synthetic abundant than ALT. However, in plasma AST is
and metabolic functions, LFT may be ordered cleared more rapidly (t½ 16-18 hours) than ALT (t½
by clinicians as a standard order for non-specific 42–48 hours). Consequently, the upper reference
symptoms (such as fever, fatigue, nausea, abdominal limit for ALT is higher (55 U/L) than that for ALT
pain, muscle pain, joint pain and weight loss) or as (45 U/L). These aminotransferases may be increased
part of general health screening for opportunistic in patients presenting with cirrhosis, chronic
discovery of occult disease. Clinicians may also order hepatitis, alcoholic hepatitis, acute viral hepatitis
LFT to confirm their pre-clinical suspicion of specific and toxic ischemic injury. Marked increase of the

80 Proceedings of Singapore Healthcare  Volume 19  Number 1  2010

 Liver Function Tests (LFTs)

Fig. 1. Typical serum AST or ALT values for various liver conditions.

aminotransferases (>15 times the upper normal) for distinguishing bone from liver source of
suggests acute hepatitis and hepatoxicity such ALP; heat lability is of historic interest only.
as acetaminophen overdose. The diagnosis for A bone specific ALP immunoassay (Ostase,
alcoholic hepatitis is supported by the finding of Beckman-Coulter) is available but costly and thus
a ratio of AST to ALT of at least 2:1 and gamma- not widely used.
glutamyl-transpeptidase (GGT) that is twice the
normal level3. The AST:ALT ratio may also be used Another canalicular enzyme, GGT corroborates the
to differentiate between different conditions: ALP increase in biliary disease. Moreover, GGT is
high ratio in hepatitis C with cirrhosis, liver normal in bone disease. Hepatic GGT production
metastases and HCV with cirrhosis versus low ratio is increased with alcohol intake and has been used
in acute inflammation and cholestasis4. The log to indicate alcoholism or alcoholic liver disease.
of aminotransferase range in U/L against normal However, GGT is elevated with medications
subjects, and the diagram may be used to guide (anticonvulsants and histamine receptor blockers),
interpretation of ALT and AST results (Fig. 1.)5. prostate disease, obesity, diabetic nephropathy
and hypertension. Hence, this mitigates against its
ALP use as a routine LFT.
ALP is found in the liver, bone, kidney, intestine and
placenta. Serum ALP is thus a mixture of different Bilirubin
ALP isoenzymes and can be fractionated by Serum bilirubin is a mixture of α, β, γ and δ fragments
electrophoresis. In normal serum, ALP comprises which are unconjugated, singly conjugated, doubly
the liver and bone moieties; bone ALP is heat conjugated and covalently bound to albumin,
labile. Liver ALP, found on canalicular surfaces, respectively. Although δ bilirubin measurement is
is raised in any condition of biliary obstruction available, it has not gained wider utility. In most
(intrahepatic and extra-hepatic). In hepatocyte cases a total bilirubin assay suffices for LFT, but
injury, ALP is often normal or marginally elevated. fractionation may be required in isolated increases
This feature is used as a guide to differentiate liver in bilirubin and neonatal jaundice. Direct bilirubin
parenchymal disease from biliary dysfunction. It (DB) refers to the conjugated bilirubins that react
is unusual to require ALP isoenzyme fractionation directly with the diazo reagent, while indirect

Proceedings of Singapore Healthcare  Volume 19  Number 1  2010 81

 Laboratory Insights

bilirubin is a derived value obtained from the blood sample after an intramuscular injection
difference of the total bilirubin and DB. DB assays or a haemolysed blood sample due to a difficult
measure only 70–90% of the conjugated and phlebotomy or haemoconcentration from
δ bilirubins, and may underestimate the severity prolonged tourniquet application. The cytosolic
of jaundice. Direct measures of conjugated and ALT and cytosolic and mitochondrial forms of AST
unconjugated bilirubin is available (Vitros BuBc, are released into the plasma when the red blood
Johnson & Johnson), but its use is confined to a cells are damaged. Haemoconcentration will also
minority of labs. compromise albumin results.

Serum bilirubin is useful in separating the causes of Additional Lab Tests

jaundice. In prehepatic jaundice due to haemolysis, Prothrombin time (PT) is a marker of hepatic
unconjugated bilirubin is increased with little or synthetic function. It is an early indicator of the
no increase in conjugated bilirubin. In hepatic transition of chronic hepatitis to cirrhosis. PT is
and post-hepatic jaundice, there is increased also a parameter that is used to compute the
conjugated and δ bilirubins. MELD score for considering patients with cirrhosis
for transplantation. Adjunct clinical lab tests to
Albumin investigate liver disease include GGT to confirm
Albumin is synthesised in the liver and is an alcohol abuse; antimitochondrial antibodies to
indictor of liver function. However, serum albumin evaluate autoimmune hepatitis; serologic tests
levels change slowly due to the long half life of to confirm Hepatitis A, B and C; AFP for liver
albumin together with the capacity of the liver to cancer; and iron studies for the investigation of
synthesise albumin at twice the health basal rate haemochromatosis. However, it must be noted that
to compensate for decreased synthetic capacity or clinical lab tests do not prove cirrhosis, fibrosis and
albumin losses. Albumin is decreased by trauma, tumour without imaging and liver biopsy6. A new
inflammatory conditions and malnutrition. enhanced liver fibrosis (ELF) immunoassay (Advia,
Siemens) comprising a mixture of 3 fragments of
Limitations of LFTs liver matrix components — hyaluronic acid (HA),
The American Gastroenterological Association N-terminal fragment of procollagen III (P3NP)
(AGA) position statement on liver chemistry tests and tissue inhibitor of matrixmetalloproteinase-1
provides guidelines for a rational approach to the (TIMP-1) is gaining currency in Europe as a non-
interpretation and further diagnostic evaluation invasive marker of liver fibrosis.
of patients with abnormal liver chemistry tests1.
The AGA has also provided a technical review References
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the clinical context of the patient. AST and ALT are Liver function tests, p. 125–149.
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often normal in patients with cirrhosis as they are
Function Tests. Am Fam Physician. 1999;59(8):2223–30.
released into the blood when liver cell membranes 6. Jacobs DS, Demott WR, Grady HJ, Horvat RT, Huestis DW,
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OH: Lexi-Comp Inc; 1996. Liver profile, p. 161–3.
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2. O’ Brien CB. The hospitalised patient with abnormal liver
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due to pre-analytical errors such as obtaining the

82 Proceedings of Singapore Healthcare  Volume 19  Number 1  2010

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