INTERPRETATION OF HEPATIC FUNCTION TESTS.pdf

HEPATIC FUNCTION TESTS
(INTERPRETATION)

 Liver is the largest organ in the body (1.2-1.5 kgs.).
 2 sources of blood supply to the liver:
• Hepatic artery (from the aorta; supplies O2-rich arterial blood);
• Portal veins (venous outflow of intestine and spleen);
Hepatic Function Tests (LFTs)
 Most often used to determine:
• Presence and type of liver disease;
• Extent and progression of liver disease;
LFTs analyze:
1] Test of excretion by the liver
 Reported as:
• Total Bilirubin [ Unconjugated (Indirect) + Conjugated (Direct)]
• Direct Bilirubin (Conjugated)

2] Evaluation of synthesis in
the liver
Albumin
Pre-albumin
Globulin
Total Protein
Prothrombin time
Cholesterol & esters
3] Enzyme activity evaluation
Serum transaminases
* AST (SGOT)
* ALT (SGPT)
Serum alkaline phosphatase
[ALP]
Lactate Dehydrogenase
[LDH]
ɣ-glutamyl transpeptidase
[GGTP]

Serum Bilirubin:
 Is a breakdown product of Hb; is predominant in the bile;
• Indirect form (bound to albumin; H2O-insoluble );
• Direct form (secreted into bile);
 Hepatobiliary function + RBC turnover rate determines the
extent of bilirubin conjugation and excretion.
 Hyperbilirubinaemia may not always cause clinically apparent
jaundice (usually visible >60 umol/l).
 Unconjugated bilirubin is water-insoluble (doesn’t affect the
patient’s urine colour);
 Conjugated bilirubin can pass into the urine (as urobilinogen,
causing the urine to become darker).

 Combination of the urine colour and stools indicate the cause
of jaundice:
• Normal urine + normal stools = pre-hepatic cause
• Dark urine + normal stools = hepatic cause
• Dark urine + pale stools = post-hepatic cause (obstructive)
Unconjugated hyperbilirubinaemia (causes):
• Haemolysis (haemolytic anaemia)
• Impaired hepatic uptake (drugs, congestive cardiac failure)
• Impaired conjugation (Gilbert’s syndrome)
Conjugated hyperbilirubinaemia (causes):
• Hepatocellular injury
• Cholestasis

Albumin
 Synthesized in the liver;
 Helps to bind water, cations, fatty acids, and bilirubin;
 Helps to maintain oncotic pressure of blood.
↓ed Albumin (causes):
• Liver disease (e.g. cirrhosis);
• Inflammation – triggers acute phase response – temporarily
decreases albumin production by liver;
• Protein-losing enteropathies or nephrotic syndrome;

Prothrombin time (PT)
 Is a measure of the blood’s coagulation tendency;
 ↑ed PT (in absence of other 2° causes such as anticoagulant drug use
and vitamin K deficiency) indicates liver disease and dysfunction.
 The liver is responsible for the synthesis of clotting factors. So,
hepatic pathology can impair this process resulting in ↑ed PT time.
AST/ALT ratio
 Used to determine the likely cause of LFT derangement:
 ALT > AST (a/w chronic liver disease);
 AST > ALT (a/w cirrhosis and acute alcoholic hepatitis);
• What about ASpartate aminoTransferase?

ALanine Amino Transferase (ALT)
 Highly concentrated within hepatocytes;
 Enters the blood after hepatocellular injury (useful marker or
indicator of hepatocellular injury).
ALkaline Phosphatase (ALP)
 Highly concentrated in liver, bile duct and bone tissues;
 Often ↑ed in liver pathology due to ↑ed synthesis in response to
cholestasis (useful indirect marker or indicator of cholestasis);

 > 10x ↑ in ALT and < 3x ↑ in ALP (predominantly hepatocellular
injury);
[E.g., viral hepatitis, metabolic liver diseases, drug or alcohol
toxicity and autoimmune hepatitis]
 < 10x ↑ in ALT and > 3x ↑ in ALP (cholestasis);
[E.g., Bile stones, cholestatic drug-induced liver injury]
 It is possible for patients to have both hepatocellular injury and
cholestasis.

Gamma-Glutamyl Transferase (GGT)
 If ALP ↑es, then it is important to review the level of GGT.
 ↑ed GGT:
• biliary epithelial damage and bile flow obstruction;
• in response to alcohol and drugs (phenytoin);
 A markedly ↑ed ALP + ↑ed GGT is highly suggestive of cholestasis.

Isolated ↑ ALP
 ↑ ALP + normal GGT (suspicion of non-hepatobiliary pathology);
 ALP is also present in bone (anything that leads to ↑ed bone
breakdown can ↑ ALP).
 Isolated ↑ ALP (causes):
• Bony metastases or primary bone tumours (e.g. sarcoma)
• Vitamin D deficiency
• Recent bone fractures; Renal osteodystrophy;

Jaundice patient w/ normal ALT and ALP levels
 An isolated ↑ in bilirubin (suggestive of pre-hepatic cause of
jaundice);
 Isolated ↑ in bilirubin (causes):
• Gilbert’s syndrome (most common cause);
• Haemolysis;

Gluconeogenesis
 Is a metabolic pathway resulting in the generation of glucose from
certain non-carbohydrate carbon substrates.
 The liver plays a significant role in gluconeogenesis.
 Assessment of serum blood glucose can provide an indirect
assessment of the liver’s synthetic function.
 Gluconeogenesis is one of the last functions to become impaired
in the context of liver failure.

Typical LFT patterns a/w acute hepatocellular damage, chronic
hepatocellular damage and cholestasis
↑ (mild impairment); ↑↑(severe impairment);

Acute hepatocellular injury (common causes):
 Poisoning (paracetamol overdose)
 Infection (Hepatitis A and B)
 Liver ischaemia
Chronic hepatocellular injury (common causes):
 Alcoholic fatty liver disease
 Non-alcoholic fatty liver disease
 Chronic infection (Hepatitis B or C)
 Primary biliary cirrhosis

IMPORTANT POINTERS
 ALP is also produced outside the liver by the bones, placenta,
kidneys, and gut. Hence, ALP may be ↑ed in the presence of normal
liver health, most commonly due to bone disease or pregnancy.
 GGT is induced by alcohol and other drugs and so lacks specificity for
many liver diseases.
 Bilirubin ↑ es with increasing severity of liver disease.
 In cases of ↑ed bilirubin or clinical jaundice, we should consider
haemolysis (Hb breaks down to form bilirubin. Lipid-soluble,
unconjugated bilirubin is conjugated in the liver, making it water-
soluble, and then excreted into bile).
 ALT > AST (viral hepatitis); AST > ALT (alcoholic liver disease);

Imp. Pointers (contd’.)
 Mildly ↑ed ALT and AST: Chronic hepatitis C or B, acute viral
hepatitis, NAFLD, hemachromatosis, autoimmune hepatitis,
medications, alcohol-related liver injury, Wilson’sdisease.
 Severe ALT and AST ↑es: Severe acute liver cell injury: acute viral
hepatitis, ischemic hepatitis or other vascular disorder, toxin-
mediated hepatitis, acute autoimmune hepatitis;
 Hyperbilirubinemia: Hemolysis; Gilbert syndrome, bile duct
obstruction, primary biliar cirrhosis, primary sclerosing cholangitis,
benign recurrent cholestasis, hepatitis, cirrhosis, medications,
sepsis, total parenteral nutrition, Dubin-Johnson syndrome,
medications (isoniazid, rifampicin, amoxicillin/clavulanic acid,
phenylpropylamine, allopurinol, cimetidine, and fluvastatin);

 ALT and AST ↑ with strenuous exercise and muscle injury.
 Meals have no effect on ALT and AST levels.
 ALT is ↑ed with higher BMI.
 ALP levels ↑ with food intake, pregnancy, and smoking.
 Bilirubin levels ↑ with fasting.
 Light exposure ↓es bilirubin.
 Compare to what degree the ALT and ALP are raised.
Hepatocellular injury (marked ↑ ALT compared to ALP);
Cholestatic injury (marked ↑ ALP compared to ALT);

 ↑ed GGT: Alcohol consumption, obesity;
 ↑ed ALP and GGT: Bile duct obstruction, 1° biliary cirrhosis,
1° sclerosing cholangitis, benign recurrent cholestasis, infiltrative
liver diseases (sarcoidosis, lymphoma, metastasic disease);
 Isolated ↑ed ALP: Bone disease, pregnancy, chronic renal failure,
lymphoma, congestive heart failure;
 ↑ed PT (expressed in seconds or as INR) and ↓ed albumin:
Severe hepatic synthetic dysfunction; indicates progression to
cirrhosis or impending hepatic failure;

PT, Clotting factors, Vit.K
 The PT is dependent on clotting factors’ activity.
 Clotting factors are produced by the liver.
 Production of clotting factors is dependent on adequate vit.K.
 Clotting may also be prolonged by vitamin K deficiency.
 PT is a good indicator of liver function (acute and chronic cases) if
vit.K levels are normal and in absence of anticoagulants usage(e.g.
warfarin).
International Normalized Ratio (INR)
 The INR also reflects clotting and liver synthetic function.
 INR is standardized across all laboratories in the world.
 Liver function must be quite severely impaired to affect PT or INR.
 Mild liver disease will most likely have normal values of PT and
INR.

Always consider hemolysis if the serum bilirubin
levels are elevated.
• In cases of ↑ed bilirubin or clinical jaundice, we
should consider haemolysis (Hb breaks down to
form bilirubin. Lipid-soluble, unconjugated bilirubin
is conjugated in the liver, making it water-soluble,
and then excreted into bile).

INTERPRETATION OF HEPATIC FUNCTION TESTS.pdf

A typical ‘liver screen’ includes the following:
 LFTs; Coagulation screen; 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 deficiency);
 Serum Copper (to rule out Wilson’s disease);
 Ceruloplasmin (to rule out Wilson’s disease);
 Ferritin (to rule out haemochromatosis);

INTERPRETATION OF HEPATIC FUNCTION TESTS.pdf

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INTERPRETATION OF HEPATIC FUNCTION TESTS.pdf