Interpreting liver function tests

Question 1

What are the main roles of the liver?

Answer 1

detoxification - metabolism and excretion of drugs
process and storage of - amino acids, proteins (most produced by the liver, except immunoglobulins), carbohydrate, cholesterol and vitamins
synthesis of bile acids -cholesterol catabolism
catabolic site for many of the hormones - insulin, glucagon, oestrogens, glucocorticoids, GH, PTH, conversion of VITd to 25-OHD
contribution to the immune response

Question 2

What routine biochemical tests are there to assess liver function?

Answer 2

bilirubin 
hepatocellular enzymes - ALT (AST - less specific)
hepatobiliary enzymes - ALP, gamma-GT
albumin 
total protein

Question 3

What clinical questions need to be asked when assessing the liver?

Answer 3

is the liver disease present?
what is the aetiology?
what is the severity?
can the disease be monitored?

Question 4

What are the possible symptoms in which liver disease may present?

Answer 4

jaundice
abdo distension
ankle swelling - odema due to altered albumin
haemetemesis
pruritis
pale stools and dark urine - due to obstruction

Question 5

What important factors should you ask about in the history if you suspect liver disease?

Answer 5

recent travel 
duration of illness
drug use
alcohol consumption 
family history 
weight loss 
BMI - fatty liver

Question 6

What are the normal ranges for:

• total bilirubin
• ALP
• ALT
• AST
• Albumin
• gamma-GT (M and F)

Answer 6

• total bilirubin = <21 micromol/L
• ALP = 30-130 U/L = also found in bone and intestine, varying levels in adolescents
• ALT = 5-40 U/L
• AST = 5-43 U/L
• Albumin = 35-50g/L
• gamma-GT (M and F) = 9-50u/l and 9-40u/l

Question 7

What is bilirubin a product of?

Answer 7

haem catabolism - 85%
red cell precursors
myoglobin 
cytochromes
peroxidase 
daily production = 170-300 micromol/day

Question 8

What are the different types of hyperbilirubinaemia?

Answer 8

pre-hepatic = haemolytic conditions cause raised bilirubin (unconjugated) but with no bilirubinaemia

hepatic = bilirubin (unconjugated and conjugated) is elevated at some stage of most hepatobiliary disease (with biliruburia)

post-hepatic = raised bilirubin (conjugated) due to bile outflow obstruction - bilirubinaemia

Question 9

When is jaundice noticeable?

Answer 9

about 50 micromol/L

Question 10

What are the main causes of pre-hepatic unconjugated hyperbilirubinaemia?

Answer 10

Production from haem
- haemolysis - hereditary, acquired or rapid turnover in neonates

Reduced delivery of unconjugated bilirubin in plasma
- R sided CCF, portocaval shunt

Reduced uptake of unconjugated bilirubin across liver membrane

• competitive inhibition e.g. drugs
• Gilbert’s (UGT1A1*28)
• Sepsis, fasting

Question 11

What are the main causes of post-hepatic conjugated hyperbilirubinaemia?

Answer 11

Reduced secretion of conjugated bilirubin into the canaliculi

• hepatocellular disease - hepatitis, intrahepatic cholestasis
• drugs

Reduced drainage
- extrahepatic obstruction - stones, carcinoma, stricture, atresia

Sclerosing cholangitis intrahepatic obstruction

• drugs
• granuloma
• PBC
• tumour

Question 12

What are the different types of jaundice?

Answer 12

haemolytic
cholestatic
hepatocellular

Question 13

What criteria suggest haemolytic jaundice?

Answer 13

bilirubin usually <75 micromo/L 
no bilirubin in urine 
Reticulocytosis 
Reduced Hb 
Reduced haptoglobin 
LDH may increase

Question 14

What criteria suggest cholestatic jaundice?

Answer 14

Bilirubin may be really increased
Bilirubin in urine
ALP > x3 ULN
AST, LDH and ALT moderately increased

Question 15

What criteria suggest hepatocellular jaundice?

Answer 15

AST + ALT significantly increased
Bilirubin increased later
Bilirubin in urine
ALP raised later

Question 16

What are the differences between AST/ALT and ALP/gamma-GT?

Answer 16

AST and ALT = cytosolic enzyme (50% AST is mitochondrial)
- increased with hepatic damage

ALP / gamma-GT = membrane bound glycoprotein enzyme
- increased with cholestatic damage

Question 17

What happens to the enzymes in liver cell damage ?

Answer 17

AST released more quickly in liver disease
ALT more chronic release and may reflect length of disease
- fatty liver causes rises in ALT more often than AST

Question 18

What happens to the enzymes in cholestasis ?

Answer 18

ALP increased
gamma-GT increased - can be induced by lots of alcohol
Alcohol and Gamma-GT
- increases are noted BUT increased gamma-GT is often found in pts with increased triglyceride and fatty liver, diabetes

Question 19

Where is AST found?

Answer 19

in the liver - predominantly mitochondrial
in the muscle - predominantly cytoplasmic
in red blood cells - gross haemolysis

Question 20

Where is ALT found?

Answer 20

cytoplasmic enxyme

Question 21

Where is ALP found in ?

Answer 21

bone
placenta
growth phases in childhood and adolescence
when bone is remodelled (after fracture)

Question 22

What are plasma proteins usually included in?

Answer 22

LFTs

• NOT specific
• albumin - hypoalbuminaemia very common in hospitalised patients
• immunoglobulinaemia can reflect liver disease- also a general indicator of chronic infection

Question 23

What are some other examples of plasma proteins?

Answer 23

caeruloplasmin = reduced in wilson’s disease (problem with copper metabolism)
alpha-1 antitrypsin - protease inhibitor, deficiency states lead to liver/lung disease

coagulation proteins - short half life, use INR

Question 24

What liver function test is used for liver tumours?

Answer 24

AFP (alpha-fetoprotein) 75% cases

Question 25

What liver function tests are used for metabolic liver disease?

Answer 25

alpha-1 antitrypsin deficiency haemochromatosis iron, total iron binding capacity (transferrin) ferritin Wilson's disease - serum copper, caeruloplasmin

Question 26

What is the AST:ALT ratio?

Answer 26

normal ration of AST to ALT = ABOUT 0.8 | >1 = EVIDENCE OF CIRRHOSIS

Question 27

What would you want to check if you suspected hepatocellular disease?

Answer 27

check transaminase > about 5xULN | ALP normal or slightly increased

Question 28

What would you want to check if you suspected cholestatic disease?

Answer 28

ALP >200U/L | Transaminase normal or slightly raised <200U/L

Question 29

If there was mixed liver disease what would you expect to see?

Answer 29

significant increases in ALP and transaminase | both greater than 200U/L

Question 30

``` Case 1: - 24 F, no meds - mild jaundice, pallor, malaise, 6/12 hx heavy irregular menstrual periods - no spleno or hepatomegalu investigations: - TProt: 77g/l - Alb : 35g/L - ALP: 110U/L - ALT: 42 U/L - Bili: 48 umol/L ``` What are the differential diagnosis?

Answer 30

haemolytic disease iron deficiency anaemia gilbert's syndroe hepatobiliary disease on futher testing: - Tbil: 48 - Cbil: 11 - LDH: 149U/L (increased) - Iron: 5 (decreased) iron deficiency anaemia

Question 31

What is gilbert's syndrome?

Answer 31

``` autosomal dominant (7%) intermittant mild jaundice with unconjugated bilirubin periods of fasting and illness ```

Question 32

``` Case 2: - 14 M treated for broken arm - mildly jaundiced - splenomegaly Investigations: - Tprot: 75 - Alb: 40 - ALP: 98 - ALT: 14 - Bili: 68 - Hb:10.3 - Cbil: <5 - LDH: 560U/L (increased) - haptoglobin: 0.1 (reduced) ``` What are the differential diagnoses?

Answer 32

unconjugated hyperbilirubinaemia, LDH and haptoglobin=> haemolytic process hereditary spherocytosis

Question 33

``` Case 3: - 35 F - 4/52 hx malaise, anorexia, upper abdo pain - dark urine - overt jaundice for 3/7 Investigations: - Tprot - 71 g/dl - Alb- 42 - ALP - 180 - GGT - 331 - ALT 2090 - AST 1788 - bilirubin - 126 What is the potential diagnosis? ```

Answer 33

Serology: - hep A and C negative - hep b positive

Question 34

``` Case 4: - 65 M - AAA repair - after OP developed severe chest pain and shock - BP unrecordable - Acute MI INVESTIGATIONS: - T prot: 69 to 63 - ALP: 125 to 13 - GGT: 50 to 169 - ALT: 43 to 955 - AST: 30 to 812 - Bili: 14 to 17 Rapid development of hepatocellular damaage, no jaundice and hypoxic damage to liver What are the main causes of acute hepatocellular damage? ```

Answer 34

hypoxia chemicals drugs acute hepatitis

Question 35

``` Case 5: - 49 F - pneumonia and septicaemia - started on erythromycin and 5 days later become jaundiced and complained of pruritis - no pain investigations: - TProt: 72 to 69 -ALP: 120 to 328 - GGT: 43 to 402 - ALT: 24 to 67 - AST: 30 TO 89 - Bili:13 to 156 ``` What is the diagnosis?

Answer 35

Erythromycin associated cholestasis re-challenge the patient when LFTs have normalised stopped it and when back to normal

Question 36

What is the classical picture of obstructive jaundice?

Answer 36

significantly elevated ALP with mild elevations of transaminase stone in common bile duct