Liver Function Tests

Related Subjects: | Chronic liver disease | Cirrhosis | Alkaline phosphatase (ALP) | Liver Function Tests | Ascites Assessment and Management | Budd-Chiari syndrome | Autoimmune Hepatitis | Primary Biliary Cirrhosis | Primary Sclerosing Cholangitis | Wilson disease | Hereditary Haemochromatosis | Alpha-1 Antitrypsin (AAT) deficiency | Non alcoholic steatohepatitis (NASH) | Spontaneous Bacterial Peritonitis | Alcoholism and Alcoholic Liver Disease

These are not tests of liver function but liver damage or cholestasis. Normal LFTs does not mean a normal liver. The three main causes of an acute and severe derangement of all liver enzymes are hepatic ischaemia, viruses or drugs/toxins

About

• Raised LFTS suggests liver damage
• Some are more marker of liver damage
• Markers of Function
  • Bilirubin (normal if low)
    • Unconjugated (95% Bound to albumin): high with haemolysis
    • Conjugated (Bound to glucuronide): High with obstruction
    • Total serum bilirubin of >35 micromol/L, people will have icteric sclera
    • Total Bilirubin > 40 micromol/L they will be clinically jaundiced
    • Bilirubin is potentially toxic at high levels and can cause kernicterus
    • This can cause brain damage particularly in neonates.
    • Elevated Bilirubin
      • Haemolysis (inherited or acquired)
      • Viral hepatitis
      • Drug-induced liver injury
      • Biliary obstruction
        • USS: Dilated CBD/Bile ducts: MRCP or ERCP
        • USS: Non dilated bile ducts: Consider liver biopsy
      • Rotor, Crigler-Najjar, Dubin-Johnson and Gilbert’s syndromes
      • Cirrhosis and choledocholithiasis
      • Gilbert's syndrome (enzymatic deficiency)
  • Albumin (Abnormal if low)
    • Reduced hepatic synthesis
    • It is an acute phase reactant and falls in inflammatory states
    • Excess renal loss or GI loss
    • Malnutrition
  • Prothrombin time (abnormal if prolonged)
    • Impaired synthesis of I, II, V, VII and X
  • Urea (Abnormal if low)
  • Ammonia (Low if normal function)
• Markers of Damage
  • AST
  • ALT: ALT is present in high concentrations in the liver and to a lesser extent in skeletal muscle, kidney and heart.
  • LDH
• Markers of Cholestasis
  • Raised Bilirubin
  • Raised ALP
  • Raised GGT
• Markers of Alcohol
  • Raised GGT
  • AST:ALT ratio >2 suggests alcoholic liver disease

Assessing patient with abnormal LFTs

• History Medication and Recent antibiotics
• All recent medication including herbal
• Travel: where, town or countryside
• Water sports, lakes, canoeing (leptospirosis)
• Intravenous or recreational drug use (hepatitis B/C)
• Alcohol: amount CAGE and any DTs
• Sexual history and Blood transfusions prior to 1990 (HIV)
• Associated symptoms, Fevers, rigors, vomiting, pale stools, dark urine, pruritis, weight loss, abdominal pain
• Signs of underlying chronic liver disease or malignancy
• Any sepsis, acute liver failure, Coagulopathy, encephalopathy, jaundice

Causes of Liver damage

• Viral hepatitis B and C
• Alcoholic liver disease
• Drug induced hepatotoxicity
• Ischaemia and liver congestion
• Obstructive jaundice
• NAFLD with T2DM (raised AST > ALT)

Prothrombin time (PT)

• The liver produces clotting factors I,II,V,VII and X
• Prognostic significance in Paracetamol overdose and liver failure
• Prolonged PT may also be due to Vitamin K deficiency so give Vitamin K and any residual issue is impaired Liver function
• Give oral or Vitamin K 5-10 mg slow IV
• Raised PT seen with Warfarin therapy reversible with Vit K

Albumin

• Produced at a rate of about 120 mg/kg/day
• Production rate is reduced by cytokines as well as liver disease and cirrhosis
• Low albumin leads to ascites and oedema
• Low with non-liver causes - sepsis, malnutrition, nephrotic syndrome
• Half-life is about 21 days

Urea

• Low in liver disease perhaps due to impaired liver metabolism
• High in an acute GI bleed /high GI protein load

Ammonia

• May be high in acute Fulminant liver failure
• Correlated with encephalopathy

Bilirubin

• Breakdown product of Haem metabolism
• Elevated conjugated Bilirubin identifies cholestasis - pancreatic carcinoma, gallstones, PBC
• Elevated unconjugated Bilirubin suggests Haemolysis, Gilbert's syndrome

Alkaline Phosphatase (ALP)

• Released by Bile canaliculi
• This are markers of obstruction
• Also produced by bone and placenta

Gamma Glutamyl transferase (GGT)

• Microsomal enzyme and inducible by drugs and alcohol
• Tends to rise in parallel with ALP
• Hepatobiliary disease, Alcohol, Phenytoin, Barbiturates

AST and ALT

• Transaminases - AST to ALT ratio is greater than 2:1 strongly suggests alcohol)
• ALT is more liver specific
• Normal - seen in end stage liver failure with massive loss of hepatocytes
• Mildly elevated AST and ALT (<100 iu/L)
  • Chronic Viral Hepatitis (B/C)
  • Fatty liver disease
  • Haemochromatosis, Cholelithiasis
• Moderate elevated transaminases (100-300 iu/L)
  • Above causes, Alcoholic hepatitis (AST >> ALT)
  • Non-Alcoholic Steatohepatitis
  • Autoimmune hepatitis, Wilson's disease
• Major elevated (>300 iu/L)
  • Drug toxicity, Paracetamol (Acetaminophen) overdose
  • Acute viral hepatitis
  • Autoimmune liver disease
  • Ischaemic liver insult
  • Toxins e.g. amanita phalloides
  • Flare of Hepatitis B

Liver Disease	Abnormal test	Diagnostic test
Autoimmune hepatitis	Elevated AST and ALT	ANA anti-smooth muscle ab
Primary biliary cirrhosis	Elevated ALP	Antimitochondrial antibody
Alcoholic liver disease	AST/ALT >2	Improves with abstention
Primary sclerosing cholangitis	Raised ALP	MRCP pANCA
Haemochromatosis	Elevated AST and ALT	Ferritin, Genetic Analysis
Alpha-2 antitrypsin	Elevated AST and ALT	Phenotype analysis
Wilson's disease	Elevated AST and ALT	ALP low, Ceruloplasmin low, High urine copper, High liver copper
Hepatitis A	Elevated AST and ALT	Anti HAV IgM
Hepatitis B	Elevated AST and ALT	HbSAg, Anti HBc IgM, HbeAg, HBVDNA
Hepatitis C	Elevated AST and ALT	Anti HCV, HCV RNA

Investigations

• Routine bloods including coagulation and glucose
• Send a full non invasive liver screen
  • Viral serology: HbSAg, hepatitis C antibody, hepatitis A IgM, herpes simplex virus, CMV, HIV. If hepatitis B virus serology is positive, send hepatitis D IgM
  • Immunology: Check Anti-mitochondrial antibodies, anti-smooth muscle antibodies, anti-nuclear antibodies, Serum immunoglobulins
  • Glucose, Cholesterol
  • Metabolic and genetic
    • Caeruloplasmin, serum free copper levels if < 55 yo
    • Serum ferritin, transferrin saturation
    • A1 antitrypsin phenotype
    • Paracetamol and salicylate levels
    • Alpha fetoprotein - hepatocellular carcinoma
  • Send ABG and consider arterial ammonia
  • Contact your lab before sending. The sample will need to be sent on ice.
  • Be vigilant for signs of sepsis.
  • Blood cultures: consider low threshold for broad spectrum antibiotics, especially if there is evidence of evolving acute liver failure
  • Have a low threshold for starting N-acetylcysteine and commence NAC if any suspicion of paracetamol overdose
  • Request US abdomen: Liver echotexture, focal liver lesion, biliary obstruction, gallstones, portal vein patency
  • If obstructive jaundice then MRCP or ERCP. ERCP is an invasive procedure. The patient will need to be fasted, and anticoagulants stopped. Check FBC and clotting screen the day before the procedure
• Dilated bile ducts: consider ERCP or MRCP
• Liver biopsy (can be via jugular if coagulopathy)

Pathology