Hyperbilirubinemia MCQs With Answer provide B. Pharm students a focused, practical way to actively master bilirubin metabolism, causes of jaundice, diagnostic methods, and therapeutic interventions. This curated set emphasizes pharmacological aspects—UGT1A1 enzyme function, drug-induced cholestasis, phototherapy mechanisms, exchange transfusion indications, and bilirubin-binding agents—along with genetic disorders like Gilbert and Crigler–Najjar syndromes. Questions target serum bilirubin interpretation (direct vs. indirect), laboratory assays, neonatal management, and drug interactions relevant to hepatic clearance. Ideal for exam preparation and clinical application, these MCQs reinforce core concepts and treatment strategies critical to pharmacy practice. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which fraction of bilirubin is typically elevated in hemolytic disorders?
- Conjugated bilirubin
- Unconjugated bilirubin
- Delta bilirubin
- Water-soluble bilirubin conjugates
Correct Answer: Unconjugated bilirubin
Q2. Which enzyme is primarily responsible for hepatic conjugation of bilirubin?
- UDP-glucuronosyltransferase (UGT1A1)
- Cyclooxygenase (COX-1)
- N-acetyltransferase (NAT2)
- Glutathione S-transferase (GST)
Correct Answer: UDP-glucuronosyltransferase (UGT1A1)
Q3. Gilbert syndrome is best characterized by which of the following?
- Severe neonatal hyperbilirubinemia and need for transplant
- Mild unconjugated hyperbilirubinemia triggered by fasting or stress
- Conjugated hyperbilirubinemia with black liver pigment
- Impaired hepatic uptake of bilirubin with renal excretion
Correct Answer: Mild unconjugated hyperbilirubinemia triggered by fasting or stress
Q4. Crigler–Najjar syndrome type I differs from type II by which feature?
- Type I responds to phenobarbital while type II does not
- Type I has complete absence of UGT1A1 activity; type II has partial activity
- Type I causes conjugated hyperbilirubinemia; type II causes unconjugated hyperbilirubinemia
- Type I is benign; type II is typically fatal in infancy
Correct Answer: Type I has complete absence of UGT1A1 activity; type II has partial activity
Q5. Which laboratory finding suggests conjugated (direct) hyperbilirubinemia?
- Elevated indirect bilirubin with normal urine color
- Increased serum direct bilirubin and dark urine
- High serum unconjugated bilirubin and low alkaline phosphatase
- Isolated elevation of serum albumin-bound bilirubin
Correct Answer: Increased serum direct bilirubin and dark urine
Q6. The van den Bergh (diazo) reaction differentiates bilirubin fractions by which principle?
- Conjugated bilirubin reacts directly without solvents; unconjugated requires alcohol
- Unconjugated bilirubin reacts directly; conjugated requires heat
- Both fractions react identically in all conditions
- The test measures only total bilirubin, not fractions
Correct Answer: Conjugated bilirubin reacts directly without solvents; unconjugated requires alcohol
Q7. Which drug is known to induce UGT1A1 and lower unconjugated bilirubin levels?
- Phenobarbital
- Chlorpromazine
- Cimetidine
- Ketoconazole
Correct Answer: Phenobarbital
Q8. Phototherapy lowers neonatal bilirubin primarily by converting bilirubin to:
- Hydrophobic unconjugated bilirubin
- Water-soluble photoisomers (e.g., lumirubin)
- Delta bilirubin bound to albumin
- Conjugated bilirubin via UGT activation
Correct Answer: Water-soluble photoisomers (e.g., lumirubin)
Q9. Which condition is associated with conjugated hyperbilirubinemia and a grossly dark liver on biopsy?
- Gilbert syndrome
- Crigler–Najjar syndrome
- Dubin–Johnson syndrome
- Rotor syndrome
Correct Answer: Dubin–Johnson syndrome
Q10. A serum total bilirubin of 3 mg/dL with direct bilirubin 2.5 mg/dL indicates:
- Predominantly unconjugated hyperbilirubinemia
- Predominantly conjugated hyperbilirubinemia
- Normal bilirubin distribution
- Measurement error; direct cannot exceed total
Correct Answer: Predominantly conjugated hyperbilirubinemia
Q11. In neonatal exchange transfusion indications, which factor is most critical to consider?
- Serum albumin concentration only
- Absolute bilirubin level, age in hours, and risk factors for kernicterus
- Presence of conjugated bilirubin alone
- Urea and creatinine levels
Correct Answer: Absolute bilirubin level, age in hours, and risk factors for kernicterus
Q12. Which of the following drugs is commonly linked to cholestatic liver injury and jaundice?
- Acetaminophen at therapeutic doses
- Chlorpromazine
- Insulin
- Metformin
Correct Answer: Chlorpromazine
Q13. Increased urinary urobilinogen is most consistent with which mechanism?
- Obstructive cholestasis preventing bilirubin excretion
- Increased hemolysis with elevated unconjugated bilirubin reaching gut
- Defective hepatic uptake of conjugated bilirubin
- Primary biliary cirrhosis without hemolysis
Correct Answer: Increased hemolysis with elevated unconjugated bilirubin reaching gut
Q14. Albumin reduces bilirubin neurotoxicity primarily by what mechanism?
- Converting bilirubin to conjugated form
- Binding free unconjugated bilirubin and reducing free fraction
- Inducing UGT1A1 expression
- Inhibiting enterohepatic circulation
Correct Answer: Binding free unconjugated bilirubin and reducing free fraction
Q15. Rotor syndrome differs from Dubin–Johnson syndrome in that Rotor syndrome:
- Features black pigmented liver on histology
- Is due to defective canalicular excretion and has normal liver pigmentation
- Is an acute infectious hepatitis causing jaundice
- Always requires liver transplantation
Correct Answer: Is due to defective canalicular excretion and has normal liver pigmentation
Q16. Which transporter defect is implicated in bilirubin conjugate excretion causing Dubin–Johnson syndrome?
- MRP2 (ABCC2) impairment
- OATP1B1 loss-of-function
- BSEP (ABCB11) overactivity
- NTCP (SLC10A1) mutation
Correct Answer: MRP2 (ABCC2) impairment
Q17. A patient with obstructive jaundice would most likely have which lab pattern?
- High indirect bilirubin, normal ALP and GGT
- High direct bilirubin with elevated ALP and GGT
- Isolated elevated unconjugated bilirubin only
- Low total bilirubin with elevated AST only
Correct Answer: High direct bilirubin with elevated ALP and GGT
Q18. Free (unbound) bilirubin crosses the blood–brain barrier and causes kernicterus; which factor increases free bilirubin?
- High serum albumin concentration
- Acidosis which reduces bilirubin–albumin binding
- Hypercalcemia enhancing binding
- Hypothermia increasing UGT1A1 activity
Correct Answer: Acidosis which reduces bilirubin–albumin binding
Q19. Which prenatal condition most commonly leads to severe neonatal hyperbilirubinemia due to hemolysis?
- Maternal hypothyroidism
- Rh incompatibility (maternal anti-D antibodies)
- Maternal hyperglycemia without antibodies
- Intrauterine growth restriction without hemolysis
Correct Answer: Rh incompatibility (maternal anti-D antibodies)
Q20. Ceftriaxone can cause biliary sludge because:
- It directly inhibits UGT1A1
- It forms insoluble calcium–ceftriaxone complexes in bile
- It increases hemolysis leading to unconjugated bilirubin overload
- It causes autoimmune destruction of hepatocytes
Correct Answer: It forms insoluble calcium–ceftriaxone complexes in bile
Q21. Phenobarbital helps lower bilirubin in Crigler–Najjar type II by:
- Photolysing bilirubin into isomers
- Inducing residual UGT1A1 activity to increase conjugation
- Blocking enterohepatic circulation directly
- Binding bilirubin in plasma like albumin
Correct Answer: Inducing residual UGT1A1 activity to increase conjugation
Q22. Which statement about delta bilirubin is correct?
- Delta bilirubin is unconjugated and water-soluble
- Delta bilirubin is conjugated bilirubin covalently bound to albumin and accumulates in prolonged cholestasis
- Delta bilirubin is the main form excreted in feces
- Delta bilirubin is produced by phototherapy
Correct Answer: Delta bilirubin is conjugated bilirubin covalently bound to albumin and accumulates in prolonged cholestasis
Q23. A drug that inhibits UGT1A1 would most likely:
- Decrease unconjugated bilirubin levels
- Increase unconjugated bilirubin and risk of jaundice
- Increase conjugated bilirubin clearance
- Prevent hemolysis
Correct Answer: Increase unconjugated bilirubin and risk of jaundice
Q24. Which stool/urine finding points toward obstructive jaundice rather than hemolysis?
- Increased fecal urobilinogen and dark stool
- Pale (acholic) stools and dark urine due to conjugated bilirubin in urine
- Normal stool color and increased urinary urobilinogen
- Dark stool with no change in urine color
Correct Answer: Pale (acholic) stools and dark urine due to conjugated bilirubin in urine
Q25. In the context of enterohepatic circulation, which intervention reduces neonatal bilirubin enterohepatic reabsorption?
- Administration of oral antibiotics to reduce gut flora
- Feeding to promote intestinal motility and bilirubin elimination
- Blocking UGT1A1 in the liver
- Giving intravenous albumin to the neonate
Correct Answer: Feeding to promote intestinal motility and bilirubin elimination
Q26. Which genotype alteration is most commonly associated with Gilbert syndrome?
- UGT1A1 promoter TA insertion (UGT1A1*28) reducing expression
- Deletion of UGT1A1 gene entirely
- Mutation in MRP2 leading to export defect
- Mutation in hemoglobin causing hemolysis
Correct Answer: UGT1A1 promoter TA insertion (UGT1A1*28) reducing expression
Q27. Which therapeutic option directly removes bilirubin from the bloodstream in severe neonatal hyperbilirubinemia?
- Exchange transfusion
- Oral phenobarbital alone
- Topical corticosteroids
- Ursodeoxycholic acid administration
Correct Answer: Exchange transfusion
Q28. Which lab test is most useful to distinguish prehepatic from hepatocellular or obstructive jaundice?
- Serum amylase alone
- Fractionated bilirubin levels (direct and indirect) along with ALP and GGT
- Serum creatinine only
- Serum sodium and potassium levels
Correct Answer: Fractionated bilirubin levels (direct and indirect) along with ALP and GGT
Q29. Which of these drugs can increase bilirubin levels by causing hemolysis in G6PD-deficient patients?
- Primaquine
- Rifampicin
- Phenobarbital
- Metronidazole (in therapeutic doses for most)
Correct Answer: Primaquine
Q30. Which phototherapy wavelength range is most effective for neonatal hyperbilirubinemia?
- Infrared 800–1000 nm
- Blue-green light 460–490 nm
- Ultraviolet 200–300 nm
- Red light 620–700 nm
Correct Answer: Blue-green light 460–490 nm
Q31. Which biliary transporter mediates hepatic uptake of unconjugated bilirubin derivatives and bilirubin conjugates from blood?
- OATP (organic anion transporting polypeptides)
- P-glycoprotein (MDR1)
- SLC6A4 (serotonin transporter)
- Glucose transporter (GLUT2)
Correct Answer: OATP (organic anion transporting polypeptides)
Q32. In a patient with high total bilirubin but normal liver enzymes and no symptoms, which diagnosis is more likely?
- Acute viral hepatitis
- Gilbert syndrome or benign familial jaundice
- Choledocholithiasis causing obstruction
- Fulminant hepatic failure
Correct Answer: Gilbert syndrome or benign familial jaundice
Q33. Which mechanism best explains drug-induced cholestasis?
- Enhanced UGT1A1 activity causing rapid conjugation
- Inhibition of bile salt export pumps or canalicular transporters leading to bile retention
- Excessive secretion of bile acids into intestine
- Accelerated enterohepatic circulation clearing bilirubin
Correct Answer: Inhibition of bile salt export pumps or canalicular transporters leading to bile retention
Q34. A rise in serum conjugated bilirubin is most directly due to:
- Increased heme breakdown in spleen
- Impaired excretion of conjugated bilirubin into bile ducts
- Reduced albumin synthesis
- Excess intestinal bacterial conjugation
Correct Answer: Impaired excretion of conjugated bilirubin into bile ducts
Q35. Which of the following is a recognized pharmacologic strategy to reduce enterohepatic recycling of bilirubin?
- Administering cholestyramine to bind bile acids and bilirubin in gut
- Giving drugs that inhibit renal excretion of bilirubin
- Using UGT1A1 inhibitors to decrease conjugation
- Administering albumin-binding competitors to displace bilirubin
Correct Answer: Administering cholestyramine to bind bile acids and bilirubin in gut
Q36. In adult hemolytic anemia, which laboratory pattern is expected?
- Low indirect bilirubin and decreased reticulocyte count
- Elevated indirect bilirubin, elevated LDH, and increased reticulocyte count
- High direct bilirubin with bilirubinuria
- Elevated alkaline phosphatase with normal bilirubin
Correct Answer: Elevated indirect bilirubin, elevated LDH, and increased reticulocyte count
Q37. Which statement about bilirubin measurement units is correct?
- 1 mg/dL equals approximately 17.1 µmol/L
- 1 mg/dL equals approximately 2 µmol/L
- Conversion depends on patient age only
- Units are not standardized across labs
Correct Answer: 1 mg/dL equals approximately 17.1 µmol/L
Q38. Which of the following is true regarding kernicterus?
- It results from conjugated bilirubin deposition in the cortex
- It is more likely with high levels of unbound unconjugated bilirubin in neonates
- It is prevented by antibiotics alone
- It occurs exclusively in adults with chronic cholestasis
Correct Answer: It is more likely with high levels of unbound unconjugated bilirubin in neonates
Q39. Which intervention is used to treat immune-mediated neonatal hemolysis causing hyperbilirubinemia?
- Topical photoprotectants
- Intravenous immunoglobulin (IVIG) to reduce hemolysis
- Oral phenobarbital in the mother only
- Administering rifampicin to the neonate immediately
Correct Answer: Intravenous immunoglobulin (IVIG) to reduce hemolysis
Q40. A medical student asks which bilirubin species is water-soluble and filtered by the kidney; the correct answer is:
- Unconjugated bilirubin bound to albumin
- Conjugated bilirubin (direct) and some water-soluble photoisomers
- Delta bilirubin only
- Nonpolar unconjugated bilirubin
Correct Answer: Conjugated bilirubin (direct) and some water-soluble photoisomers
Q41. Which hepatic condition often shows marked elevation of gamma‑glutamyl transferase (GGT) together with bilirubin?
- Hemolytic anemia
- Extrahepatic biliary obstruction
- Isolated Gilbert syndrome
- Inherited Crigler–Najjar type I
Correct Answer: Extrahepatic biliary obstruction
Q42. Which medication can trigger severe jaundice in a patient with Gilbert syndrome during fasting or stress?
- Ibuprofen at low doses
- Atazanavir (a protease inhibitor known to raise unconjugated bilirubin)
- Oral contraceptives that induce UGT1A1 significantly
- Metformin
Correct Answer: Atazanavir (a protease inhibitor known to raise unconjugated bilirubin)
Q43. The primary site of bilirubin conjugation is:
- Bone marrow macrophages
- Hepatocyte endoplasmic reticulum via UGT1A1
- Renal proximal tubule cells
- Intestinal epithelial cells
Correct Answer: Hepatocyte endoplasmic reticulum via UGT1A1
Q44. Which of the following best explains why neonatal bilirubin levels rise after birth?
- Increased hepatic UGT1A1 activity immediately after birth
- Physiologic immaturity of hepatic conjugation and increased hemolysis of fetal RBCs
- Excessive renal excretion of conjugated bilirubin
- Immediate colonization with gut flora that enhances conjugation
Correct Answer: Physiologic immaturity of hepatic conjugation and increased hemolysis of fetal RBCs
Q45. Which lab or clinical feature points to hepatocellular jaundice rather than purely hemolytic jaundice?
- Markedly elevated unconjugated bilirubin with normal transaminases
- Elevated AST/ALT with mixed direct and indirect hyperbilirubinemia
- Normal liver enzymes with increased urobilinogen
- Low alkaline phosphatase with dark urine
Correct Answer: Elevated AST/ALT with mixed direct and indirect hyperbilirubinemia
Q46. In drug development, a new compound causing elevated conjugated bilirubin likely indicates:
- Enhanced hemolysis in peripheral blood
- Potential interference with biliary transporters or cholestatic potential
- Specific inhibition of intestinal flora only
- Beneficial stimulation of UGT1A1 activity
Correct Answer: Potential interference with biliary transporters or cholestatic potential
Q47. Phenobarbital therapy in neonatal jaundice is effective because it:
- Produces photochemical isomers of bilirubin
- Induces hepatic enzymes increasing glucuronidation and clearance
- Directly binds bilirubin and removes it via kidney
- Inhibits enterohepatic circulation by killing gut flora
Correct Answer: Induces hepatic enzymes increasing glucuronidation and clearance
Q48. Which clinical test helps detect immune hemolysis contributing to hyperbilirubinemia?
- Coombs (direct antiglobulin) test
- Serum ceruloplasmin
- Fecal occult blood only
- Serum amylase
Correct Answer: Coombs (direct antiglobulin) test
Q49. In prolonged cholestasis, why can conjugated bilirubin persist elevated after obstruction resolution?
- Conjugated bilirubin is irreversibly degraded in plasma
- Delta bilirubin (albumin-bound conjugates) persist due to covalent binding to albumin
- UGT1A1 permanently inactivated
- Enterohepatic circulation rapidly removes conjugated bilirubin
Correct Answer: Delta bilirubin (albumin-bound conjugates) persist due to covalent binding to albumin
Q50. Which management approach is appropriate for an adult with mild unconjugated hyperbilirubinemia due to Gilbert syndrome?
- Liver transplantation as first-line therapy
- Reassurance, avoid precipitants, and monitor; treatment rarely needed
- Aggressive phototherapy indefinitely
- Immediate exchange transfusion
Correct Answer: Reassurance, avoid precipitants, and monitor; treatment rarely needed

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