Liver Function Tests

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Liver Function Tests

• Susan Troup
• Principal Clinical Biochemist
• Queen Elizabeth Hospital
• Gateshead Health NHS Trust

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Learning objectives

• Knowledge of the anatomy and functions of the
  liver
• Understanding of the biochemical tests used to
  assess liver disease, how to interpret them, and
  confounding factors
• Knowledge of different liver diseases and the
  patterns of LFTs they produce

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Anatomy of a lobule
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Functions of the liver

• Synthesis
• plasma proteins
• clotting factors
• immune factors
• Metabolism
• carbohydrate
• protein
• lipids
• Production of bile

• Storage
• glycogen
• vitamins
• trace metals
• Detoxification and excretion
• drugs
• hormones
• toxins
• Conjugation and excretion of bilirubin

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Liver function tests

• Albumin
• Bilirubin
• GGT, ?GT, gamma glutamyl transferase
• ALP, alkaline phosphatase
• Aminotransferases
• ALT, alanine aminotransferase
• Prothrombin time/INR

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Albumin

• Reference range 34 50 g/L
• Major protein product of liver
• T1/2 20 days
• Decreased in
• Chronic liver disease
• Malnutrition
• Nephrotic syndrome
• Trauma/surgery
• Ascites

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Bilirubin

• Reference range lt20 ?mol/L
• Raised bilirubin
• Haemolysis increased breakdown of haemoglobin
• Failure of conjugation in hepatocytes
• Obstruction of biliary system

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?-glutamyl transferase (GGT)

• Reference range 5-50 u/L
• Wide distribution but most in liver and bile
  ducts
• Raised by
• Cholestasis
• Liver damage parallels ALT/AST
• Alcohol
• Drugs e.g. phenytoin

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Alkaline phosphatase (ALP)

• Reference range 30-130 u/L
• Found in
• Liver
• Bone (osteoblasts)
• Placenta
• Intestine
• Isoenzymes can be separated by electrophoresis
• Raised GGT suggests liver source for ALP

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Liver alkaline phosphatase

• Raised in
• Cholestasis/obstruction
• Hepatic tumour, abscess
• Cirrhosis
• Infiltrative hepatic disease
• Hepatitis
• Due to increased synthesis by cells lining
  biliary canaliculi

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Alanine aminotransferase (ALT)

• Alanine aminotransferase (ALT)
• Reference range 5-40 u/L
• Transferases rise in hepatic injury and fall as
  condition resolves
• Decreasing transferases may also indicate almost
  complete destruction of parenchymal cells

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Prothrombin time/INR

• PT measures rate of conversion of prothrombin
  to thrombin
• Reference range 10-15 sec
• Screens for clotting factor deficiencies
• Internationalised normalised ratio
• Compares patient to normal control
• Test the livers synthetic function

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Are these liver function tests

• ALT, Bilirubin and ALP tell us nothing about the
  FUNCTION of the liver
• These are markers of liver dysfunction or damage
• Albumin and prothrombin time may give an
  indication of the livers synthetic ability

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Why do we do LFTs

• To find out if liver disease is present?
• If so
• What is the nature of the disease?
• What is the severity of the disease?

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Liver diseases

• Acute hepatitis
• Chronic hepatitis
• Cirrhosis
• Alcohol
• Non-alcohol related fatty liver disease
• Tumours and infiltrations
• Biliary diseases

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Acute hepatitis

• Viral
• Hep A, B, C, D, E, Epstein Barr, cytomegalovirus
• Toxins
• Alcohol, paracetamol, carbon tetrachloride,
  fungal toxins
• May present with anorexia, malaise, jaundice

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Acute hepatitis

• Pre-icteric Icteric
• Plasma bili N/? ???
• ALT ??? ?
• ALP N N/?
• Urine bili ? ?
• Urine ? absent
• urobilinogen

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Chronic hepatitis

• Hepatic inflammation persisting for gt 6 months
• Causes
• Auto-immune hepatitis, chronic Hep B or C
  infection, alcohol
• ? ALT, other LFTs normal until cirrhosis develops

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Cirrhosis

• Irreversible scarring of the liver
• Causes
• Chronic alcohol excess, auto-immune hepatitis,
  primary biliary cirrhosis, persistent Hep B or C,
  inherited metabolic disease
• LFTs may be normal until late in the disease
• Decompensation may lead to encephalopathy
• Renal failure may occur

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Alcohol

• Hepatic steatosis (fatty liver)
• Asymptomatic hepatomegaly
• ? ALT, ? ? GGT, normal bili
• Alcoholic hepatitis
• After a binge in patients with a history of
  alcohol excess
• Cirrhosis
• Chronic alcohol ingestion
• Prognosis good if patient can abstain
• from alcohol

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Non-alcoholic fatty liver disease

• Causes
• Obesity, diabetes, parenteral feeding,
  starvation, inherited metabolic diseases, drugs
• May be asymptomatic
• ALT ? ? , GGT ? , bili normal, albumin normal
• Fatty infiltration on liver biopsy
• Generally resolves, but may progress

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Tumours and infiltrations

• Common site for tumour metastases
• Primaries less common
• Cirrhosis
• Hep B or C
• Carcinogens
• Infiltrative conditions
• lymphomas, amyloidosis
• Often not jaundiced
• ALP may be increased

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Biliary Diseases

• Primary Sclerosing Cholangitis (PSC)
• Autoimmune, inflammation and fibrosis of bile
  ducts, over time become blocked
• Eventually can cause cirrhosis and liver failure
• 10-30 develop cholangiocarcinoma
• Gall Stones
• Mostly cholesterol or bilirubin
• Cause biliary colic and obstruction

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Isolated increases in LFTs

• The next few slides relate to the finding of an
  isolated slight increase in individual LFTs in a
  asymptomatic patient

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Isolated increase in ALP

• Check both liver and bone profile
• lt1.5x ULN
• Repeat in 1-3 months unless clinical suspicion
  of disease
• gt1.5x ULN
• Repeat in 6 months
• If remains elevated further investigation
• gt3x ULN
• Further investigation

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Isolated increase in ALT

• Exclude - Excess ETOH
• - Diabetes
• - Hypertriglyceridaemia
• If lt2x ULN repeat in 1-3 months
• If remains elevated 1.5-3x ULN after 6 months,
  further investigation
• If gt3x ULN or, risk factors or clinical features
  of liver disease, further investigation required
  (next slide)

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Isolated increase in ALT

• First line - FBC
• - Autoantibodies
• - Ferritin
• - Hep B surface antigen
• - Hep C antibody
• Second
• line - Alpha-1-antitrypsin
• - Caeruloplasmin
• - Anti-TTG antibodies
• - Liver ultrasound

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Isolated increase in bilirubin

• lt1.5x ULN
• Repeat in 1-3 months unless clinical suspicion
  of disease
• gt1.5x ULN ?Gilberts
• Check LDH to exclude haemolysis
• Check conjugated bilirubin if lt30 of total,
  suggests Gilberts
• gt3x ULN Clinical disease likely
• Check conjugated bilirubin
• if gt50 suggest liver ultrasound
• if lt30 ?haemolysis, suggest LDH, FBC and
  reticulocyte

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Isolated increase in GGT

• lt3x ULN
• Repeat in 1-3 months unless clinical suspicion of
  disease
• gt5x ULN
• Consider liver ultrasound if no cause apparent

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Learning objectives

• Knowledge of the anatomy and functions of the
  liver
• Understanding of the biochemical tests used to
  assess liver disease, how to interpret them, and
  confounding factors
• Knowledge of different liver diseases and the
  patterns of LFTs they produce

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Questions?