What is the appropriate treatment for a 32-year-old male with chronic hepatitis B (HBV), presenting with fatigue, decreased level of consciousness (LOC), jaundice, severe knee pain, and laboratory results showing elevated alanine transaminase (ALT), aspartate transaminase (AST), bilirubin, amylase, and international normalized ratio (INR), who extensively uses paracetamol (acetaminophen)?

Treatment: N-Acetylcysteine (NAC) is the Appropriate Therapy

This patient requires immediate intravenous N-acetylcysteine (NAC) for acetaminophen-induced acute liver failure, regardless of the time since ingestion or the presence of chronic hepatitis B. 1, 2

Clinical Reasoning

This 32-year-old presents with classic acute liver failure (ALF) features:

• Decreased level of consciousness (encephalopathy)
• Jaundice with elevated bilirubin
• Coagulopathy (INR 2.0)
• Markedly elevated transaminases (ALT/AST)
• History of extensive paracetamol use for chronic knee pain 1

The combination of chronic hepatitis B with superimposed acetaminophen toxicity creates a particularly high-risk scenario, as concurrent acetaminophen use in patients with underlying viral hepatitis is associated with worse outcomes and higher mortality. 3

Why NAC is the Correct Answer (Option B)

Guideline-Based Recommendations

NAC should be administered systematically in ALL cases of acute liver failure, whatever the suspected etiology. 1 This is a GRADE 1+ (strong) recommendation with 100% agreement from experts. 1

• The American Society of Anesthesiologists recommends NAC for acute liver failure regardless of etiology to improve morbidity and mortality 2
• NAC improves overall survival (76% versus 59%, OR = 2.30, P <0.0001) 2
• Transplant-free survival increases significantly with NAC (64% versus 26%, OR = 4.81, P < 0.0001) 2

Immediate Administration Protocol

Do not await acetaminophen level results before initiating NAC treatment. 4 The FDA-approved dosing regimen is:

• Loading dose: 150 mg/kg IV over 1 hour 4
• Maintenance: 70 mg/kg every 4 hours for 17 doses 4
• Continue until clinical improvement or transplant evaluation 1, 2

Why This Patient Specifically Needs NAC

1. Extensive paracetamol use with severe hepatotoxicity (high ALT/AST) indicates acetaminophen as the precipitating factor 1, 5
2. INR 2.0 with encephalopathy defines serious acute liver failure requiring immediate NAC 1, 6
3. Chronic HBV background makes acetaminophen toxicity more dangerous, with higher mortality risk 3
4. NAC provides multiple protective mechanisms including improved tissue oxygen delivery, antioxidant effects, and anti-inflammatory properties 2

Why Other Options Are Incorrect

Option A: IV Corticosteroids - NOT Indicated

• No guideline recommends corticosteroids for acetaminophen-induced ALF 1
• Corticosteroids are reserved for autoimmune hepatitis, not drug-induced liver failure 1
• May worsen infection risk in immunocompromised state of ALF 1

Option C: Entecavir for Acute HBV - Wrong Diagnosis

• This is NOT acute hepatitis B flare; this is acetaminophen toxicity superimposed on chronic HBV 1
• Entecavir is indicated for chronic HBV with high viral load and active inflammation, not for acute drug-induced liver failure 1
• The clinical picture (extensive paracetamol use, rapid onset over 2 days, very high transaminases) points to acetaminophen toxicity 1, 5
• Chronic HBV patients in immune inactive phase don't suddenly develop ALF from viral reactivation alone 1

Option D: Plasmapheresis - Not Standard Therapy

• Plasmapheresis is not recommended in standard ALF management guidelines 1
• No evidence supports plasmapheresis for acetaminophen-induced liver failure 1
• Standard supportive care with NAC is the evidence-based approach 1, 2

Critical Monitoring Requirements

While administering NAC, implement comprehensive monitoring: 1, 6

• Blood glucose every 2 hours (hypoglycemia risk from hepatic dysfunction) 1, 6
• Encephalopathy grade assessment frequently (more valuable than ammonia levels) 1, 6
• Maintain serum sodium 140-145 mmol/L to prevent cerebral edema 1, 6
• Daily coagulation parameters (PT/INR, Factor V) 1, 6
• Arterial blood gas and lactate (pH <7.3 indicates poor prognosis) 6
• Hepatic Doppler ultrasound and echocardiography to assess hemodynamics 1

Transplant Evaluation Criteria

Contact transplant center immediately if: 1, 6

• INR >2.0 with encephalopathy and acute kidney injury (already present in this patient) 6
• Arterial pH <7.3 after adequate volume resuscitation 6
• PT >100 seconds with creatinine >3.4 mg/dL and grade III/IV encephalopathy 6
• Progressive liver failure despite NAC therapy 1, 2

Common Pitfalls to Avoid

1. Never delay NAC while awaiting acetaminophen levels - start immediately on clinical suspicion 1, 4
2. Don't assume chronic HBV is the primary problem - the acute presentation with extensive paracetamol use points to drug toxicity 5, 3
3. Avoid nephrotoxic drugs including NSAIDs during management 6
4. Don't use benzodiazepines or metoclopramide - these worsen encephalopathy 1
5. Monitor for hypoglycemia aggressively - check glucose at least every 2 hours 1, 6

Supportive Care Alongside NAC

• Crystalloid fluids as first choice for volume expansion 1
• Norepinephrine for refractory hypotension 1
• Stress ulcer prophylaxis per ICU protocols 1
• Empirical broad-spectrum antibiotics if worsening encephalopathy or SIRS 1
• Standard lung protective ventilation if intubation required 1

The elevated amylase mentioned suggests possible multi-organ involvement, which further supports the diagnosis of severe acetaminophen toxicity with systemic effects. 1 This reinforces the urgency of NAC administration and intensive monitoring.