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Liver Function Tests

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Liver Function Tests Susan Troup Principal Clinical Biochemist Queen Elizabeth Hospital Gateshead Health NHS Trust * Although can occur in severe acute liver damagae ... – PowerPoint PPT presentation

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Title: Liver Function Tests


1
Liver Function Tests
  • Susan Troup
  • Principal Clinical Biochemist
  • Queen Elizabeth Hospital
  • Gateshead Health NHS Trust

2
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

3
Anatomy of a lobule
4
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

5
Liver function tests
  • Albumin
  • Bilirubin
  • GGT, ?GT, gamma glutamyl transferase
  • ALP, alkaline phosphatase
  • Aminotransferases
  • ALT, alanine aminotransferase
  • Prothrombin time/INR

6
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

7
Bilirubin
  • Reference range lt20 ?mol/L
  • Raised bilirubin
  • Haemolysis increased breakdown of haemoglobin
  • Failure of conjugation in hepatocytes
  • Obstruction of biliary system

8
?-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

9
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

10
Liver alkaline phosphatase
  • Raised in
  • Cholestasis/obstruction
  • Hepatic tumour, abscess
  • Cirrhosis
  • Infiltrative hepatic disease
  • Hepatitis
  • Due to increased synthesis by cells lining
    biliary canaliculi

11
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

12
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

13
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

14
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?

15
Liver diseases
  • Acute hepatitis
  • Chronic hepatitis
  • Cirrhosis
  • Alcohol
  • Non-alcohol related fatty liver disease
  • Tumours and infiltrations
  • Biliary diseases

16
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

17
Acute hepatitis
  • Pre-icteric Icteric
  • Plasma bili N/? ???
  • ALT ??? ?
  • ALP N N/?
  • Urine bili ? ?
  • Urine ? absent
  • urobilinogen

18
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

19
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

20
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

21
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

22
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

23
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

24
Isolated increases in LFTs
  • The next few slides relate to the finding of an
    isolated slight increase in individual LFTs in a
    asymptomatic patient

25
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

26
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)

27
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

28
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

29
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

30
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

31
Questions?
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