Lecture 11 Liver function tests

Question 1

What are the three major categories of liver blood tests?

Answer 1

Hepatocellular injury markers (ALT/AST); cholestatic markers (ALP/GGT/bilirubin); synthetic function markers (albumin/INR)

Question 2

Why is the term ‘liver function tests’ misleading?

Answer 2

Most tests reflect injury, not function; only albumin and INR assess true synthetic function

Question 3

Which enzymes is most specific for cholestatic injury markers ?

Answer 3

ALP, GGP, Bilirubin

Question 4

Which enzymes is most specific for hepatocellular injury markers ?

Answer 4

ALT, AST

Question 5

Which enzymes is most specific for synthetic function markers ?

Answer 5

Albumin, INR

Question 6

What does AST > ALT typically suggest?

Answer 6

Alcohol-related liver disease or established cirrhosis

Question 7

What does ALT/AST >1000 IU/L indicate?

Answer 7

Severe acute hepatocellular necrosis (e.g., paracetamol toxicity, acute viral hepatitis, ischaemic hepatitis)

Question 8

What does a raised ALP with raised GGT indicate?

Answer 8

Cholestasis of hepatic origin

Question 9

What does raised ALP with normal GGT suggest?

Answer 9

Bone disease rather than liver disease

Question 10

What is GGT particularly sensitive to?

Answer 10

Alcohol intake and enzyme-inducing drugs

Question 11

Which bilirubin type is water-soluble?

Answer 11

Conjugated bilirubin

Question 12

What causes dark urine in jaundice?

Answer 12

Renal excretion of conjugated bilirubin

Question 13

What bilirubin level causes visible jaundice?

Answer 13

Above 50 µmol/L

Question 14

What pattern suggests pre-hepatic jaundice?

Answer 14

Isolated unconjugated bilirubin elevation

Question 15

What does low albumin indicate in chronic liver disease?

Answer 15

Reduced hepatic synthetic function

Question 16

Why does hypoalbuminaemia worsen ascites?

Answer 16

Reduced oncotic pressure causing fluid leakage

Question 17

How does low albumin affect drug handling?

Answer 17

Increases free fraction of highly protein-bound drugs, raising toxicity risk

Question 18

What does a prolonged INR indicate?

Answer 18

Impaired synthesis of vitamin K-dependent clotting factors

Question 19

Why is INR a good marker of acute deterioration?

Answer 19

Factor VII has a short half-life so INR rises quickly

Question 20

What does lack of INR improvement after vitamin K suggest?

Answer 20

True hepatic synthetic failure

Question 21

What pattern indicates hepatocellular injury?

Answer 21

Markedly raised ALT/AST with mild ALP rise

Question 22

What pattern indicates cholestasis?

Answer 22

Raised ALP + GGT + bilirubin with mild ALT/AST rise

Question 23

What pattern indicates synthetic failure?

Answer 23

Low albumin + raised INR

Question 24

How does liver disease affect drug absorption?

Answer 24

Slower gastric emptying, reduced splanchnic perfusion, impaired bile salt secretion

Question 25

How does hypoalbuminaemia affect drug distribution?

Answer 25

Increases free drug levels and toxicity risk

Question 26

How is drug metabolism altered in cirrhosis?

Answer 26

Reduced CYP450 activity and reduced first-pass metabolism causing accumulation

Question 27

Why is drug excretion impaired?

Answer 27

Reduced biliary clearance and common renal impairment

Question 28

Which metabolic phase is most impaired in liver disease?

Answer 28

Phase I (CYP450 oxidation/reduction)

Question 29

Which metabolic phase is relatively preserved?

Answer 29

Phase II (conjugation)

Question 30

Which benzodiazepines are safer in liver disease?

Answer 30

Lorazepam, oxazepam, temazepam

Question 31

Why do high-extraction drugs accumulate in cirrhosis?

Answer 31

Reduced hepatic blood flow and impaired first-pass metabolism

Question 32

Why are highly protein-bound drugs risky in cirrhosis?

Answer 32

Low albumin increases free drug concentration

Question 33

Name three high-risk protein-bound drugs.

Answer 33

Warfarin, phenytoin, diazepam

Question 34

Give 5 classes of drugs to avoid or use with extreme caution in cirrhosis, give an example and their rational for caution

Answer 34

NSAIDS - Ibuprofen -Risk of GI bleeding, renal impairment, and worsening ascites Sedatives - Benzodiazepines, opioids - They accumulate and precipitate encephalopathy Opioids- Morphine - Constipation may worsen encephalopathy by increasing ammonia absorption ACE i or ARBs - Ramipril/losartan -They reduce renal perfusion and may trigger hepatorenal syndrome Direct hepatotoxins- Methotrexate - compounding of pre-existing hepatic injury

Question 35

What is the general dosing rule in liver disease?

Answer 35

Start low, go slow

Question 36

Why choose short-acting drugs?

Answer 36

Reduced accumulation and fewer active metabolites

Question 37

What monitoring is essential in liver disease?

Answer 37

INR, LFTs, U&Es, renal function, drug levels

Question 38

A patient with known cirrhosis presents with worsening fatigue. Their blood tests show: ALT: 32 IU/L (normal–mildly raised) AST: 35 IU/L (normal–mildly raised) ALP: 310 IU/L (significantly raised) GGT: 420 IU/L (raised) Albumin: 26 g/L INR: 1.7 Which interpretation BEST fits this pattern? A. Acute viral hepatitis B. Cholestasis with impaired synthetic function C. Drug-induced hepatocellular injury D. Haemolysis causing unconjugated hyperbilirubinaemia E. Early compensated alcoholic liver disease

Answer 38

B

Question 39

Which medication is most likely to have increased bioavailability in a patient with advanced cirrhosis due to reduced first-pass metabolism? A. Amoxicillin B. Propranolol C. Metformin D. Levothyroxine E. Enoxaparin

Answer 39

B. propranolol

Question 40

A patient with decompensated cirrhosis has developed worsening confusion and ascites. Which medication is MOST likely to require a dose reduction due to reduced hepatic clearance in advanced liver disease? A. Gentamicin B. Morphine C. Lithium D. Atenolol E. Gabapentin

Answer 40

b. morphine

Question 41

A patient with advanced cirrhosis has marked hypoalbuminaemia (albumin 24 g/L). Which medication is MOST likely to have increased free (unbound) concentration due to reduced protein binding? A. Furosemide B. Paracetamol C. Warfarin D. Salbutamol E. Amoxicillin

Answer 41

C

Question 42

A 58-year-old man with decompensated cirrhosis presents with increasing confusion and lethargy. His blood results show: Na⁺ 128 mmol/L, K⁺ 3.0 mmol/L Albumin 24 g/L INR 1.9 ALT 30 IU/L, AST 32 IU/L Ammonia mildly elevated His current medicines include: morphine modified-release, lorazepam at night, omeprazole, and lactulose 15 mL once daily. Explain the key pharmaceutical considerations when managing this presentation in relation to the blood tests and drug handling in liver disease.

Answer 42

Electrolyte abnormalities (Na⁺ 128, K⁺ 3.0) are important precipitants of hepatic encephalopathy; potassium correction is essential. Sodium (Na⁺) Normal range: 135–145 mmol/L Potassium (K⁺)Normal range: 3.5–5.0 mmol/L Low albumin (24 g/L) increases free levels of highly protein‑bound drugs, raising toxicity risk. Normal serum albumin: 35–50 g/L High INR (1.9) shows impaired synthetic function, increasing bleeding risk and affecting drug choice. Sedatives and opioids (lorazepam, morphine MR) accumulate due to reduced hepatic metabolism and worsen encephalopathy — they should be reduced or stopped. Lactulose is underdosed (15 mL once daily); needs titration to achieve 2–3 soft stools/day to treat encephalopathy effectively.