19 Sept 2026 · Case #014
Acetaminophen (paracetamol) overdose with acute liver failure
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Diagnosis
Acetaminophen (paracetamol) overdose with acute liver failure
First-line treatment
Intravenous N-acetylcysteine
How the diagnosis is reached
An ALT above 7000 U/L is not something viral or alcoholic hepatitis does, since those rarely clear a few hundred. Figures in this range mean hepatocytes dying in sheets, and the near-normal alkaline phosphatase alongside only modest bilirubin places the injury in the cells rather than the bile ducts. That leaves toxic or ischemic damage, and the ultrasound has already closed off the ischemic route by showing a normal liver with patent hepatic veins. The history is the classic staggered ingestion: an initial asymptomatic period of roughly 24 hours, then nausea and right upper quadrant pain as hepatic necrosis develops. Chronic alcohol use and poor nutrition deplete glutathione and induce CYP2E1, both of which increase susceptibility. The key trap is the undetectable drug level: after a staggered or late presentation the parent compound has already been metabolised, so a negative level does not exclude toxicity and must never be used to withhold treatment. Rising INR, hypoglycemia, lactic acidosis and encephalopathy define acute liver failure, and the combination of pH below 7.30, INR above 6.5, creatinine above 3.4 mg/dL and grade III–IV encephalopathy forms the King's College criteria for transplant referral, which is why the transplant unit is already on the phone. Intravenous N-acetylcysteine replenishes glutathione and neutralises NAPQI, the reactive metabolite doing the actual damage. It works best within 8 hours of ingestion and she is three days past that, which changes nothing: the benefit persists once liver failure is established, and it improves outcomes even in acute liver failure of other causes.
Key clinical clues
- Transaminases in the thousands with only modest bilirubin and normal ALP
- Staggered ingestion with an asymptomatic first 24 hours
- Chronic alcohol use and poor nutrition depleting glutathione reserve
- Undetectable drug level does not exclude toxicity in a late presentation
- Rising INR, hypoglycemia, acidosis and encephalopathy signal acute liver failure
The case in full
Presenting complaint
Patient history
A 23-year-old woman has two days of nausea, vomiting and right upper quadrant pain. Three days ago, after an argument, she took an unclear number of over-the-counter painkillers over an evening and the next morning, feeling well at first. She drinks most evenings and eats poorly.
Examination and observations
Physical examination
She is mildly jaundiced with marked tenderness in the right upper quadrant. She is drowsy but rousable, oriented to person only, and a flapping tremor is elicited on wrist extension.
| Parameter | Value | Reference |
|---|---|---|
| Heart rate | 116 bpmRef 60–100 | 60–100 |
| Blood pressure | 98/58 mmHg | – |
| Temperature | 36.4 °CRef 36.1–37.5 | 36.1–37.5 |
| Glasgow Coma Scale | 13Ref 15 | 15 |
Liver function tests
Laboratory results
Liver function tests are sent.
| Parameter | Value | Reference |
|---|---|---|
| AST | 8420 U/LRef 10–40 | 10–40 |
| ALT | 7260 U/LRef 7–56 | 7–56 |
| Alkaline phosphatase | 146 U/LRef 44–147 | 44–147 |
| Total bilirubin | 4.1 mg/dLRef 0.2–1.2 | 0.2–1.2 |
| Albumin | 3.4 g/dLRef 3.5–5.0 | 3.5–5.0 |
Coagulation, renal function and glucose
Laboratory results
Synthetic liver function is assessed alongside renal function, and the INR is repeated twelve-hourly from admission. Vitamin K is given, with no effect on the clotting result.
| Parameter | Value | Reference |
|---|---|---|
| INR | 3.8Ref 0.8–1.2 | 0.8–1.2 |
| Prothrombin time | 42 sRef 11–14 | 11–14 |
| Creatinine | 2.6 mg/dLRef 0.5–1.1 | 0.5–1.1 |
| Glucose | 54 mg/dLRef 70–110 | 70–110 |
| Phosphate | 1.4 mg/dLRef 2.5–4.5 | 2.5–4.5 |
Arterial blood gas
Laboratory results
An arterial sample is taken on room air while the transplant unit is contacted.
| Parameter | Value | Reference |
|---|---|---|
| pH | 7.26Ref 7.35–7.45 | 7.35–7.45 |
| Bicarbonate | 13 mmol/LRef 22–28 | 22–28 |
| pCO₂ | 29 mmHgRef 35–45 | 35–45 |
| Lactate | 4.6 mmol/LRef 0.5–2.2 | 0.5–2.2 |
Toxicology and clinical course
Clinical course
The serum drug level is now undetectable, and the team debates whether that excludes toxicity. Hepatitis A, B and C serology and an autoimmune screen are negative, and ultrasound shows a normal liver with patent hepatic veins. Her encephalopathy deepens over six hours.