What is the next management step for a patient with chronic hepatitis B (HBV), presenting with severe liver dysfunction, indicated by significantly elevated liver enzymes, hyperbilirubinemia, and an elevated International Normalized Ratio (INR), who has been extensively taking paracetamol (acetaminophen)?

Immediate Management: N-Acetylcysteine for Paracetamol-Induced Acute Liver Failure

This patient requires immediate N-acetylcysteine (NAC) administration for paracetamol-induced acute liver failure, not entecavir for hepatitis B. The clinical picture—extensive paracetamol use, liver enzymes in the thousands, elevated bilirubin, and coagulopathy (elevated INR)—is pathognomonic for paracetamol hepatotoxicity superimposed on chronic hepatitis B 1, 2.

Rationale for NAC Over Entecavir

NAC must be started immediately in any patient with suspected paracetamol ingestion who has elevated transaminases (AST/ALT >1,000 IU/L), regardless of serum paracetamol level or time since ingestion 2, 3. The American College of Emergency Physicians emphasizes that very high aminotransferase levels (>3,500 IU/L) are highly correlated with paracetamol poisoning and should raise suspicion even without clear overdose history 2.

• Entecavir is indicated for chronic hepatitis B management, not acute hepatotoxicity 1. This patient's HBV serology (HBsAg+, HBeAg-, HBcIgG+) indicates chronic inactive hepatitis B, which does not cause acute liver failure with enzymes "in the thousands" 1.

• The pattern of injury—massive transaminase elevation with coagulopathy—is characteristic of paracetamol toxicity, not HBV flare 1, 2. HBV flares typically show AST/ALT elevations but rarely reach the thousands without other precipitants 1.

NAC Administration Protocol

Start NAC immediately without waiting for serum paracetamol results 2, 4, 3:

• Loading dose: 150 mg/kg IV over 1 hour 3
• Second dose: 50 mg/kg IV over 4 hours 3
• Third dose: 100 mg/kg IV over 16 hours (total 21-hour protocol) 3

NAC remains beneficial even when started >24 hours post-ingestion, though significantly less effective than treatment within 8-10 hours 2. Treatment within 8 hours results in only 2.9% severe hepatotoxicity, versus 26.4% when treated after 10 hours 2.

Critical Monitoring Requirements

Patients with established hepatotoxicity require intensive monitoring 4:

• Blood glucose every 2 hours minimum due to hepatic dysfunction risk 4
• Coagulation parameters (PT/INR) daily or more frequently if deteriorating 4
• Arterial blood gas and lactate to assess for metabolic acidosis (pH <7.3 is a poor prognostic indicator) 4
• Renal function (creatinine, urine output) as acute kidney injury commonly develops 4
• Mental status assessment using Glasgow Coma Scale; intubate if GCS <8 4
• Serum sodium maintained 140-145 mmol/L to prevent cerebral edema 4

Transplant Evaluation Criteria

Immediate referral for liver transplantation evaluation is mandated when patients meet poor prognostic criteria 4:

• Arterial pH <7.3 after adequate volume resuscitation 4
• PT >100 seconds with creatinine >3.4 mg/dL in grade III/IV encephalopathy 4
• INR >2.0 with encephalopathy and acute kidney injury 4

This patient already has elevated INR and bilirubin with massive transaminase elevation, placing them at high risk for progression to fulminant hepatic failure 4.

Why Chronic HBV is Not the Primary Issue

Pre-existing liver disease (including chronic HBV) increases susceptibility to paracetamol toxicity but does not change the immediate management 2:

• Patients with chronic liver disease develop toxicity at lower paracetamol thresholds (as low as 4-5 g/day) 2
• The acute presentation requires NAC first; antiviral therapy for HBV can be addressed after stabilization 1
• EASL guidelines note that paracetamol-induced acute liver failure can occur as a precipitant in patients with underlying chronic liver disease 1

Common Pitfalls to Avoid

Do not delay NAC while obtaining paracetamol levels 2, 3. Low or absent paracetamol levels do not rule out paracetamol poisoning if ingestion was remote, occurred over several days (repeated supratherapeutic ingestion), or timing is uncertain 2.

Do not use the Rumack-Matthew nomogram in repeated supratherapeutic ingestion (RSTI) 3. This patient's "extensive" paracetamol use suggests RSTI rather than single acute overdose. For RSTI with AST >1,000 IU/L, mortality is 14% even with NAC treatment 2.

Avoid nephrotoxic drugs including NSAIDs 4. The patient's bilateral knee pain should not be treated with NSAIDs given the acute liver and potential renal injury 4.

Extended NAC Therapy Considerations

In cases of massive overdose, concomitant substance ingestion, or pre-existing liver disease (all present in this patient), consider continued NAC beyond the standard 21-hour protocol 3:

• Check paracetamol levels, ALT/AST, and INR after the last maintenance dose 3
• Continue NAC if paracetamol levels remain detectable, transaminases are still rising, or INR remains elevated 3
• Contact regional poison center (1-800-222-1222) for dosing guidance 3