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11/13/24, 7\:32 PM Guide | LFT interpretation

LFT interpretation

Table of contents

Introduction

Liver function tests (LFTs) are among the most commonly ordered blood tests and include\:
Alanine transaminase (ALT)
Aspartate aminotransferase (AST)
Alkaline phosphatase (ALP)
Gamma-glutamyltransferase (GGT)
Bilirubin
Albumin
This guide gives an overview of LFTs and a structured approach to their interpretation.

Why check LFTs?

LFTs can be requested for multiple reasons\:
1
To investigate patients with suspected liver disease
To monitor patients with con
To monitor the e
LFTs are often sent as part of a ‘baseline’ screening panel of investigations for patients presenting with a wide range of
symptoms, even where none of the above criteria is met.

Reference ranges

Table 1. Liver function test reference ranges
Test Reference range
ALT 3-40 iu/l
AST 3-30 iu/l
ALP 30-100 umol/l
GGT 8-60 u/l
Bilirubin 3-17 umol/l
Albumin 35-50 g/l
These reference ranges can vary between laboratories, so always check local guidelines.

ALT / AST

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes found within liver cells at high
concentrations.
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Raised ALT / AST levels in the blood occur in pathologies that cause liver cell (hepatocyte) in
raised ALT / AST levels are a marker of hepatocellular injury.
Common causes of hepatocellular injury include\:
Hepatitis (viral, alcoholic, ischaemic)
Liver cirrhosis
Drug / toxin-induced liver injury (e.g. paracetamol overdose)
Malignancy (hepatocellular carcinoma)
Hint\: The AST\:ALT ratio can help determine the aetiology of hepatocellular injury, with a >2\:1 ratio classical of alcoholic liver
disease.
2

ALP / GGT

Serum alkaline phosphatase (ALP) is derived from biliary epithelial cells (cells lining the biliary tract) and bones. 3
levels can therefore be caused by cholestasis or bone disease.
Raised ALP
Cholestasis
Cholestasis describes an interruption in the bile
gallstone disease, external compression of the biliary tract (e.g. pancreatic malignancy) or medication side e
Bilirubin may or may not be raised depending on the severity of cholestasis.
Gamma-glutamyltransferase (GGT) is found in hepatocytes and also biliary epithelial cells. 2
sensitive marker of liver damage and cholestasis.
It is a non-speci
ALP and GGT are interpreted together to localise the source of raised ALP in the blood\:
An ALP rise with normal GGT suggests bone disease (e.g. Paget’s disease, vitamin D de
An ALP rise with associated GGT rise is more suggestive of cholestasis
Hint\: An isolated GGT rise is classically associated with alcohol excess.

Bilirubin

Bilirubin is a waste product of haemoglobin breakdown. It is predominantly metabolised and excreted by the liver. Raised
levels of bilirubin in the blood will lead to a yellowing of the skin, known as jaundice.
Hint\: Jaundice is usually absent until the bilirubin level exceeds 50 micromol/L.

Bilirubin metabolism

To understand the signi
When red blood cells are broken down, unconjugated (insoluble) bilirubin is created as a waste product and binds to
albumin in the bloodstream
Hepatocytes take up unconjugated bilirubin and metabolise it to form conjugated (soluble) bilirubin
Hepatocytes excrete conjugated bilirubin into the biliary tract, where it
Gut bacteria further metabolise bilirubin in bile to form urobilinogen, which is eventually excreted in the stools as
stercobilinogen
A small amount of urobilinogen is reabsorbed from the intestine into the portal venous system, and as urobilinogen is water-
soluble, the kidney is able to excrete some of this into the urine.
Stercobilinogen gives stools their dark colour. Urobilinogen is colourless in the urine. However, if the urine is left exposed to
the air, oxidation will occur, creating a dark colour. Under normal physiological conditions, urobilinogen will be present in the
urine, however conjugated bilirubin will not be present.
Raised levels of bilirubin in the blood can be caused by\:
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Excess bilirubin production (pre-hepatic jaundice)
A breakdown in bilirubin metabolism (hepatocellular jaundice)
A blockage in the bile excretion pathway (cholestatic jaundice)

Pre-hepatic jaundice

Pre-hepatic jaundice occurs when increased red blood cell breakdown produces excess bilirubin. This can overwhelm
metabolism/excretion pathways, leading to jaundice.
The most common cause of increased red blood cell breakdown is haemolysis. Bilirubin is unconjugated in the blood, as the
hepatocytes have not yet metabolised it. The remainder of LFTs are generally normal, as the liver is otherwise working well.
Hint\: In pre-hepatic jaundice, patients are often anaemic due to excess red blood cell breakdown. The diagnosis may be
Gilbert's syndrome if no anaemia is present.
Gilbert’s syndrome
Gilbert's syndrome is a congenital disorder present in up to 5% of the population. It results from a de
glucosyltransferase, the enzyme responsible for the conjugation of bilirubin within hepatocytes.
Gilbert's syndrome classically presents following viral infection with raised bilirubin but normal LFTs/ full blood count.
The disease is benign and requires no speci

Hepatocellular jaundice

Hepatocellular jaundice occurs when hepatocytes are damaged and dysfunctional, leading to an inability to metabolise
unconjugated bilirubin from the bloodstream. This leads to high levels of unconjugated bilirubin in the blood. There will
generally also be very high ALT / AST levels, marking hepatocyte damage.
Hint\: Common causes of hepatocellular injury are covered above (hepatitis, cirrhosis, malignancy, drug or toxin insult). When
liver injury is severe, there are not enough functioning hepatocytes to metabolise bilirubin, and jaundice will develop.

Cholestatic (obstructive) jaundice

Cholestasis is an interruption in bile
build up in the blood. The bilirubin has been metabolised in the liver, and thus the bilirubin in the blood is predominantly
conjugated bilirubin. There will generally also be high ALP levels with associated high GGT, marking dysfunction of the biliary
system.
Obstructive jaundice will classically lead to dark urine and pale stools. Bilirubin cannot enter the gastrointestinal tract due to
cholestasis, leading to low stercobilinogen excretion in stools.
The bilirubin in the blood is conjugated and can be
urine a very dark colour.
Hint\: Stools may also be pale in hepatocellular jaundice, as there is decreased bilirubin metabolism/excretion, however as the
bilirubin in the blood is unconjugated, it will not be able to pass into the urine. Therefore, the urine should remain a normal
colour.
Causes of cholestasis
Cholestasis can occur due to either intrahepatic or extrahepatic biliary obstruction.
Causes of intrahepatic obstruction (obstruction of the hepatic bile canaliculi)\:
Hepatitis
Cirrhosis
Malignancy
Drugs (e.g. antibiotics, oral contraceptive pills, anabolic steroids)
Pregnancy
Causes of extrahepatic obstruction (obstruction of hepatic ducts, or distal biliary tree)\:
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Gallstones
Primary sclerosing cholangitis
Intraluminal malignancy\: cholangiocarcinoma
Extraluminal malignancy causing duct compression\: head of pancreas tumours
Split bilirubin
The split of conjugated/unconjugated bilirubin in the blood can be requested to give further clues as to the aetiology of
jaundice.
Causes of predominantly unconjugated hyperbilirubinaemia\:
Pre-hepatic jaundice (e.g. haemolysis)
Gilbert syndrome
Causes of predominantly conjugated hyperbilirubinaemia\:
Cholestasis
Hepatocellular jaundice*
*Hepatocellular jaundice can initially cause a mixed conjugated/unconjugated jaundice, but at its most severe,
unconjugated hyperbilirubinaemia is seen.

Albumin

Albumin is synthesised in the liver and helps to bind water, cations, fatty acids and bilirubin. It also plays a crucial role in
maintaining the oncotic pressure of blood. Albumin is used as a non-speci
Albumin levels can fall due to\:
Decreased albumin production\: malnutrition, severe liver disease
Increased albumin loss\: protein-losing enteropathies, nephrotic syndrome
Hint\: A decrease in the synthetic function of the liver indicates severe liver disease.
Albumin has a half-life of 20 days, so it will take time to decrease, even in severe liver disease. Further assessment of the
synthetic function of the liver can be gained by ordering a coagulation screen, as the liver is also responsible for the synthesis
of clotting factors.
Severe liver disease leads to decreased production of clotting factors and an increased prothrombin time (PT) / INR in the
absence of other causes of coagulopathy.
The liver is also responsible for gluconeogenesis, and serum blood glucose assessment can also indirectly assess the liver’s
synthetic function. However, gluconeogenesis tends to be one of the last functions to become impaired in liver failure.

LFT interpretation method

Determine the pattern of LFT derangement

The pattern of ALT to ALP rise can indicate whether the pathology is primarily cholestatic or hepatocellular\:
A greater than 10-fold increase in ALT and a less than 3-fold increase in ALP suggests a predominantly hepatocellular
injury
A less than 10-fold increase in ALT and a more than 3-fold increase in ALP suggests cholestasis
It is possible to have a mixed picture involving both hepatocellular injury and cholestasis
An isolated ALP rise without a GGT rise should raise your suspicion of bony pathology.

Assess the bilirubin

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Bilirubin is a marker of severity in acute cholestatic pathology and acute hepatocellular liver injuries. The presence of clinical
jaundice is generally an indication of severe disease requiring urgent referral to secondary care for prompt assessment and
management.
An isolated bilirubin rise without further LFT derangement suggests pre-hepatic jaundice or Gilbert’s disease.

Assess synthetic function

In severe hepatocellular injuries, the synthetic functions of the liver also become impaired, leading to decreased albumin.
Coagulation studies may show prolonged prothrombin time, and in very severe disease, serum blood glucose may be low due
to impaired gluconeogenesis.
Hint\: In chronic hepatocellular pathology (e.g. cirrhosis), the ALT / AST may return to within the normal range, however
synthetic function of the liver can be markedly impaired.

Summary table

The table below compares the typical LFT patterns associated with acute hepatocellular damage and cholestasis. A single
arrow (↑) refers to a mild impairment, and a double arrow (↑↑) refers to severe impairment.
Acute hepatocellular damage Cholestasis
ALT ↑↑ Normal or ↑
AST ↑↑ Normal or ↑
ALP Normal or ↑ ↑↑
GGT Normal or ↑ ↑↑
Bilirubin R a n g e f r o m n o r m a l t o ↑↑ R a n g e f r o m n o r m a l t o ↑↑

Further investigations

Once the pattern of LFT derangement has been established, it is essential to determine the underlying cause.
If cholestasis is suspected, an ultrasound should be arranged to assess the biliary tree for a potential site/cause of biliary
obstruction.
If hepatocellular injury is suspected, a liver ultrasound is generally arranged to assess for any structural lesions that may give
clues as to the diagnosis. If the cause is unclear, a ‘liver screen’ may be ordered to investigate further.
Liver screen
A ‘liver screen’ is a batch of blood investigations to identify a wide range of potential causes of liver disease\:
Hepatitis serology (A/B/C)
Epstein-Barr Virus (EBV)
Cytomegalovirus (CMV)
Anti-mitochondrial antibody (AMA)
Anti-smooth muscle antibody (ASMA)
Anti-liver/kidney microsomal antibodies (Anti-LKM)
Anti-nuclear antibody (ANA)
p-ANCA
Immunoglobulins – IgM/IgG
Alpha-1 Antitrypsin (to rule out alpha-1 antitrypsin de
Serum Copper (to rule out Wilson’s disease)
Ceruloplasmin (to rule out Wilson’s disease)
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Ferritin (to rule out haemochromatosis)

References

1. Coates P. L i v e r F u n c t i o n T e s t s . Australian Family Physician. March 2011. Available at [LINK].
2. UpToDate. A p p r o a c h t o t h e p a t i e n t w i t h a b n o r m a l l i v e r b i o c h e m i c a l a n d f u n c t i o n t e s t s . May 3. Patient.info Professional. A b n o r m a l L i v e r F u n c t i o n T e s t s . July 2019. Available at [LINK].
4. UpToDate. B i l i r u b i n m e t a b o l i s m . October 2022. Available at [LINK].
2023. Available at [LINK].
Source\: geekymedics.com
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