What is the next management step for a patient with known hepatitis B (HBV) and suspected paracetamol (acetaminophen) overdose, presenting with severe liver dysfunction, as evidenced by elevated liver enzymes, hyperbilirubinemia, and elevated International Normalized Ratio (INR)?

Management of Suspected Paracetamol Overdose with Acute Liver Failure

The next management step is B) N-acetylcysteine (NAC), which should be administered immediately regardless of time since ingestion, as this patient presents with acute liver failure and suspected paracetamol toxicity. 1, 2

Rationale for Immediate NAC Administration

This clinical presentation strongly suggests paracetamol-induced acute liver failure superimposed on chronic hepatitis B infection:

• Liver enzymes "in the thousands" with elevated bilirubin and INR define acute liver failure (PT ratio <50% with encephalopathy defines serious ALF), and paracetamol overdose is the leading cause of acute liver failure in developed countries 1

• NAC is the only proven antidote that reduces mortality in paracetamol-induced liver failure, decreasing mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48% 2

• NAC must be given to all patients with hepatic failure due to acetaminophen, regardless of time since ingestion (Level B recommendation), as it remains beneficial even with delayed presentation 2, 3

Why NOT Entecavir

Entecavir is inappropriate for this acute presentation because:

• The patient's HBV serology (HBsAg positive, HBeAg negative, HBc IgG positive) indicates chronic hepatitis B, not acute hepatitis B 1

• The acute deterioration with "extensive paracetamol use" and transaminases "in the thousands" is far more consistent with paracetamol hepatotoxicity than HBV flare 1

• Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with paracetamol poisoning and should prompt NAC treatment even when history is inadequate 2

Immediate Management Algorithm

Step 1: Start NAC immediately without waiting for paracetamol levels 2, 4

• Loading dose: 150 mg/kg IV in 5% dextrose over 15 minutes 4
• Second dose: 50 mg/kg over 4 hours 4
• Third dose: 100 mg/kg over 16 hours (total 21-hour protocol) 4

Step 2: Obtain serum paracetamol level urgently 1

• Low or absent levels do NOT rule out paracetamol poisoning if ingestion was remote or occurred over several days (repeated supratherapeutic ingestion) 2
• Patients often underreport actual paracetamol intake 5

Step 3: Contact liver transplant center immediately 1, 3

• Early discussion is essential when there is any evidence of liver failure 3
• Patients with severe hepatotoxicity (AST >1000 IU/L) or coagulopathy require ICU-level care and early transplant hepatology consultation 2

Step 4: Continue NAC beyond standard protocol 2, 4

• In cases of suspected massive overdose or preexisting liver disease (this patient has chronic HBV), consideration should be given to continued NAC beyond 21 hours 4
• If acetaminophen levels are still detectable, or if ALT/AST are still increasing or INR remains elevated after the last maintenance dose, dosing should be continued 4

Critical Clinical Pitfalls

Do not delay NAC while awaiting paracetamol levels - NAC should be started immediately in any case of acute liver failure where paracetamol overdose is suspected or possible, even with inadequate history 2

Do not assume chronic HBV is the cause - the clinical picture (extensive paracetamol use, transaminases in thousands) strongly suggests paracetamol toxicity, which requires specific antidotal therapy 1

Do not stop NAC prematurely - in this patient with established liver failure, NAC should be continued until transaminases are declining and INR normalizes 2

Monitor for complications of acute liver failure including encephalopathy, coagulopathy, renal failure, and metabolic derangements requiring ICU-level supportive care 1, 6