Question
An 82-year-old woman with cognitive impairment is reviewed shortly after treatment for a resistant urinary tract infection. Her family notices new yellowing of her skin and sclera. Her baseline confusion is unchanged.
Liver tests show:
- Bilirubin: 48 µmol/L
- ALP: 190 U/L
- ALT: 30 U/L
- GGT: 110 U/L
- Albumin: 39 g/L
The pattern suggests predominantly cholestatic liver injury. Which recently prescribed antimicrobial is the most likely cause?
A. Cefalexin
B. Fosfomycin
C. Co-amoxiclav
D. Doxycycline
E. Gentamicin
Answer
Co-amoxiclav
Explanation
The biochemical pattern is cholestatic: bilirubin, ALP and GGT are elevated, while ALT is relatively normal.
Co-amoxiclav (amoxicillin–clavulanate) is a classic and important cause of drug-induced cholestatic hepatitis. The risk is particularly associated with the clavulanic acid component, and it is more commonly encountered in older adults.
A useful MRCP distinction is:
- Cholestatic pattern: ↑ALP and ↑GGT disproportionately more than ALT.
- Hepatocellular pattern: marked ↑ALT/AST relative to ALP.
- Mixed pattern: significant elevation of both.
Important drug associations
Drugs classically causing cholestasis
- Co-amoxiclav
- Flucloxacillin
- Erythromycin
- Chlorpromazine
- Combined oral contraceptive pill
- Anabolic steroids/testosterone
- Sulfonylureas
- Fibrates
Drugs more associated with hepatocellular injury
- Paracetamol
- Isoniazid
- Pyrazinamide
- Sodium valproate
- Phenytoin
- Statins
- Amiodarone
- Methyldopa
- Nitrofurantoin
A particularly useful exam contrast is co-amoxiclav → cholestatic injury, whereas nitrofurantoin → more commonly hepatocellular or autoimmune-like hepatitis.
Summary for quick exam revision
Drug-induced liver injury can present as hepatocellular, cholestatic, or mixed liver damage. A cholestatic pattern is suggested by a disproportionate rise in ALP and GGT compared with ALT and AST. Co-amoxiclav is one of the classic and most frequently tested causes of drug-induced cholestatic hepatitis. The clavulanic acid component is particularly implicated in the liver injury. Cholestatic injury may develop during treatment or even after the antibiotic course has finished. Older age increases the likelihood of co-amoxiclav-associated cholestatic liver injury. Flucloxacillin and erythromycin are other important antibiotics associated with cholestasis. Chlorpromazine, combined oral contraceptives, anabolic steroids, sulfonylureas and fibrates can also produce a cholestatic pattern. In contrast, paracetamol toxicity typically causes severe hepatocellular injury with very high aminotransferases. Anti-tuberculous drugs such as isoniazid and pyrazinamide also classically cause hepatocellular injury. Nitrofurantoin is more strongly associated with hepatocellular or autoimmune-like hepatitis than with isolated cholestasis. In an elderly patient who develops jaundice soon after antibiotics, always review the medication history carefully. A raised bilirubin with high ALP/GGT and relatively preserved ALT should immediately suggest cholestasis. In an MRCP question linking a recent antibiotic to this biochemical pattern, co-amoxiclav is a key answer to remember.