Jaundice and elevated ALT in a woman on tuberculosis treatment
A pharmacovigilance case for causality assessment: work out which drug is responsible, grade the reaction's severity and seriousness, and defend a causality category using the WHO-UMC causality assessment.
WHO-UMC causality assessment
- Framework
- WHO-UMC causality assessment
- You decide
- Suspect drug, reaction, severity, seriousness, causality
The case
Case Presentation
A 40-year-old woman presented to the clinic with a 1-week history of nausea, vomiting, and jaundice. She was diagnosed with pulmonary tuberculosis 6 weeks ago and had been started on a standard four-drug anti-TB regimen: isoniazid 300 mg once daily, rifampicin 600 mg once daily, pyrazinamide 1500 mg once daily, and ethambutol 800 mg once daily. She was also taking pyridoxine 10 mg once daily and a combined oral contraceptive pill. She had no history of alcohol use, herbal remedies, or known liver disease.
On examination, she was deeply icteric, afebrile, and had tender hepatomegaly. There were no stigmata of chronic liver disease.
Investigations revealed: ALT 900 U/L, AST 800 U/L, ALP 180 U/L, total bilirubin 85 µmol/L, direct bilirubin 60 µmol/L, and INR 1.3. Viral hepatitis serologies (hepatitis A, B, C, and E) were negative. Autoimmune liver serologies (antinuclear antibody, anti-smooth muscle antibody) were negative. Abdominal ultrasound showed a normal liver size, no biliary dilation, and no gallstones.
All anti-TB medications were withheld on admission. Within 48 hours, her nausea resolved, and her liver function tests began to improve. One week after stopping the drugs, her ALT had fallen to 200 U/L, and her bilirubin to 30 µmol/L. A rechallenge with isoniazid at a reduced dose of 50 mg daily was performed. Within 24 hours, she developed nausea again, and her ALT rose to 500 U/L with bilirubin rising to 45 µmol/L. Isoniazid was discontinued, and she improved. The other anti-TB drugs were reintroduced sequentially without recurrence of symptoms.
The clinical picture is consistent with drug-induced liver injury. The temporal relationship, improvement on dechallenge, and recurrence on rechallenge point to a specific agent as the cause.
What you are asked to do
- Identify which of the patient's drugs is the suspect, and say why the others are not.
- Name the reaction and grade its severity.
- Decide whether it is serious by regulatory criteria, which is not the same as severe.
- Assign a causality category under the WHO-UMC causality assessment and justify it from the timeline, the dechallenge and the alternative causes.
- State the management and what should be reported.
The suspect drug and the graded answer are deliberately not on this page: working them out is the exercise.
Log in to assess "Jaundice and elevated ALT in a woman on tuberculosis treatment"
A free account opens the trainer: name the suspect drug, grade the reaction and commit to a causality category, then see how your assessment compares and why.
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Educational content for students and clinicians in training. It does not replace professional judgement, local protocols or current prescribing information.