Abnormal LFTs GP CME North/Fri_Room11_1400_Patrick GP...¢  2014. 6. 13.¢ ...

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Transcript of Abnormal LFTs GP CME North/Fri_Room11_1400_Patrick GP...¢  2014. 6. 13.¢ ...

  • Abnormal LFTs

    GP CME 2014 Workshop Fri 55 mins

    Dr Alasdair Patrick

    Macmurray Center

    GP CME 2014

    http://www.cmdhb.org.nz/ http://www.cmdhb.org.nz/ http://www.google.co.nz/url?url=http://drugdiscovery.com/viewdetails.php?linkid=490&title=Autologous-immune-cell-therapy-to-be-tested-in-liver-cancer-patients&rct=j&frm=1&q=&esrc=s&sa=U&ei=s0-WU6f7JIKakQXQuoFg&ved=0CCkQ9QEwCg&usg=AFQjCNEHofeaKUsPnSi2sxHmA1drKRowgA http://www.google.co.nz/url?url=http://drugdiscovery.com/viewdetails.php?linkid=490&title=Autologous-immune-cell-therapy-to-be-tested-in-liver-cancer-patients&rct=j&frm=1&q=&esrc=s&sa=U&ei=s0-WU6f7JIKakQXQuoFg&ved=0CCkQ9QEwCg&usg=AFQjCNEHofeaKUsPnSi2sxHmA1drKRowgA

  • Dr Alasdair Patrick


    http://www.sgh.com.sg/ http://www.sgh.com.sg/ http://www.auckland.ac.nz/ http://www.auckland.ac.nz/ http://www.cmdhb.org.nz/ http://www.cmdhb.org.nz/ http://upload.wikimedia.org/wikipedia/commons/7/77/HRM.jpg http://upload.wikimedia.org/wikipedia/commons/7/77/HRM.jpg

  • Overview

    • Liver Function Tests

    – Cholestasis

    – Hepatocellular / Hepatitic

    • Tests of Liver Synthetic Function

    – Bilirubin, Albumin & INR

    • Clinical aspects

    • Cases

    • Cirrhosis

    – Middlemore Cirrhosis Audit

  • Normal Liver Anatomy

    Portal Vein

    Hepatic Artery

    Bile Duct

    Central Vein

  • Liver Function Tests (ULN)

    Nature of liver disease


    ALP (110)

    GGT (60)


    ALT (45)

    AST (45)

    Synthetic Function

    Bilirubin (

  • Patterns of raised LFT’s

    A purely cholestatic or purely hepatitic picture is uncommon

    Cholestatic ALT / ALP < 2

    Mixed ALT / ALP 2 - 5

    Hepatitic ALT / ALP > 5

    [ Ratio = ALT (x ULN) / ALP (x ULN)]

  • Cholestatic Enzymes –

    Alkaline phosphatase (ALP)

    • Produced in many tissues

    • Raised levels usually come from the biliary

    epithelium, bones, or placenta

    • If GGT normal unlikely hepatic source

    • Cholestasis causes increased synthesis of ALP

    and “leakage” of ALP in to the circulation

  • Cholestatic Enzymes –

    Gammaglutamyl transpeptidase (GGT) • Found in cell membranes throughout the body including

    hepatocytes and biliary epithelium

    • Levels are not raised in bone disease or pregnancy

    • Raised serum levels almost always have a liver origin (usually relating to cholestasis or fatty liver)

    • Serum levels can be elevated in the absence of liver disease due to enzyme induction by anticonvulsants (phenytoin) or EtOH

  • Causes of Cholestasis

    • Bile duct obstruction – Stones, tumour, surgery, parasites

    • Drugs – Clavulanic acid, Flucloxacillin, Erythromycin

    • Liver congestion / heart failure

    • Sepsis / systemic inflammatory disorders

    • Hormonal – Pregnancy, OCP

    • Chronic biliary disorders – Primary Biliary Cirrhosis, Primary Sclerosing Cholangitis

    • Inherited conditions – Biliary atresia, Cystic fibrosis

  • Cholestasis

    Normal Stones & dilated CBD

  • Cholestasis



  • Hepatocellular –

    Alanine Aminotransferase (ALT) • Catalyses the formation of pyruvate in the


    • Found in many tissues but by far the highest levels are in the liver

    • Elevated levels are relatively specific for liver disease

    • More sensitive marker of liver disease in chronic viral hepatitis than the AST

  • Hepatocellular –

    Aspartate Aminotransferase (AST) • Catalyses the formation of oxaloacetate in the

    cell cytosol and mitochondria

    • Found in many tissues but high levels in liver and muscle (cardiac & skeletal)

    • Elevated levels are not as specific for liver disease as an elevated ALT

    • Less sensitive marker of hepatic inflammation than ALT

  • Hepatocellular Damage


    • Viral hepatitis – EBV, HAV, HBV

    • Drugs & herbal remedies – Paracetamol OD

    • Ischaemic / hypoxic


    • Autoimmune (AIH)

    • Wilson’s disease, Budd Chiari Syndrome, AFLP

    Chronic (> 6 months)

    • Viral hepatitis – HBV, HCV

    • Fatty liver (NALFD)

    • EtOH (AFLD)

    • Drugs

    • Haemochromatosis

    • Autoimmune

    • Wilson’s

  • Transaminases – Rules of thumb

    • Chronic liver disease - ALT & AST are usually only mildly elevated ( typically 1.5 - 3 x ULN) - May be normal

    • Ratio AST / ALT ratio is < 1 in most liver disease – Alcohol related hepatitis is the exception where the ratio is

    usually > 2

    • The degree of elevation of the does not correlate well with the degree of histological damage in the liver

    • Levels may go in to the many thousands acutely and the liver recover completely

    • Falling levels usually denote recovery but are an ominous sign if the liver synthetic function is worsening

    • Levels < 10x ULN are non-specific

  • Causes: Transaminases > 1000 IU / L

    • Ischaemic hepatitis (shock)

    • Acute viral hepatitis

    – HAV, HBV

    • Drugs

    – Paracetamol OD, halothane, Carbemazepine

    [Alcoholic hepatitis ALT & AST < 300 IU/L]

  • Bilirubin

    Two primary sources

    Indirect (unconjugated): old red cells, removed by the spleen, sent to the liver

    Liver “adds” glucuronic acid, making these cells water soluble for excretion; now called direct (or conjugated)

  • Synthetic Function –

    Bilirubin • 80% comes from breakdown of haemoglobin

    – Taken up by hepatocytes and conjugated with glucuronic acid and excreted in bile

    • Normally > 95% of serum bilirubin is unconjugated (indirect); if conjugated - hepatobiliary diseases

    • Only conjugated (direct) bilirubin can be excreted in the urine

    • Unconjugated hyperbilirubinaemia may occur due to over production of bilirubin (haemolysis) or inherited disorders of bilirubin conjugation (Gilbert’s syndrome)

  • Bilirubin and Prognosis

    • Poor sensitivity for detecting liver dysfunction

    – Large reserve capacity of the liver to remove bilirubin without the development of hyperbilirubinaemia

    • In acute cholestatic disease (stone disease) hepatocyte synthetic function is normal and the degree of hyperbilirubinaemia does not influence prognosis

    • In viral hepatitis, alcoholic hepatitis and PBC the serum bilirubin does correlate with the degree of injury on biopsy and the prognosis

  • Synthetic Function –


    • Made in the liver (30g/day)

    • Quantitatively the most important protein in the

    blood (500g in body fluids), important role in

    maintaining colloid osmotic pressure

    • Serum albumin level is determined by the rate of

    synthesis, rate of loss / degradation and the

    volume of distribution

  • Albumin

    • A low serum albumin is a good indicator of

    liver synthetic failure in the presence of

    chronic liver disease, however other

    causes of hypoalbuminaemia need to be


    • Renal loss (Nephrotic syndrome)

    • Protein-calorie malnutrition

    • Haemodilution (raised)plasma volume

  • Synthetic Function –


    • Most clotting factors are synthesised in the liver

    – Liver transplantation is a surgical cure for


    • In the setting of both acute and chronic liver

    failure the INR is a very useful indicator of liver

    synthetic function and prognosis, however other

    causes of a raised INR need to be excluded: • Vitamin K deficiency (prolonged cholestasis)

    • Increased clotting factor consumption (DIC)

    • Warfarin therapy

  • PR/INR

    • In chronic liver failure INR rarely rises above 2.0

    • In acute or fulminant liver failure the INR may rise rapidly to very high levels (>10), this is associated with a very poor prognosis and liver transplanation should be considered

    • Even an INR of 1.3 in the setting of an acute severe hepatitis is of concern and should be repeated after 6-8 hrs

  • LFT’s & Liver Failure

    Acute (FHF) • ALT & AST usually >


    • INR & Bilirubin rise rapidly

    • Alb falls rapidly

    • Patient unwell for hours or days

    • Death within days of cerebral oedema, sepsis or multi-organ failure

    Chronic (Cirrhosis) • ALT & AST usually < 200

    • INR & Bilirubin rise slowly

    • Alb falls slowly

    • Patient unwell for months or years

    • Death from variceal haemorrrhage, sepsis, encephalopathy or other complications

  • Clinical aspects

    Please call out what these signs are!!

  • Examination Findings

    Dupytrons Contracture

  • Exam