What is the diagnosis and treatment for a 45-year-old female patient with jaundice, altered sensorium, nausea, vomiting, and decreased urine output, who has a history of excessive paracetamol (acetaminophen) consumption, and lab results showing hyperbilirubinemia, elevated liver enzymes (AST/ALT), coagulopathy (INR 3.2), and impaired renal function, with positive viral markers for Hepatitis B (HBV) and Hepatitis E (HEV)?

Diagnosis

This patient has acute liver failure (ALF) secondary to paracetamol (acetaminophen) overdose with superimposed chronic hepatitis B and E co-infection, complicated by hepatic encephalopathy (Grade 2-3), acute kidney injury, and coagulopathy.

The diagnosis is paracetamol-induced ALF based on the following key features 1, 2:

• History of excessive paracetamol consumption with temporal relationship to symptom onset (7 days prior to admission) 2
• Massive transaminase elevation (AST 3200, ALT 4100 IU/L) - levels >3,500 IU/L are highly correlated with paracetamol poisoning even without clear overdose history 1, 3
• Severe coagulopathy (INR 3.2, PT ratio <50%) defining serious ALF 4
• Hepatic encephalopathy with altered sensorium (GCS 12/15), asterixis, and disorientation 4, 2
• No prior liver disease - ALF occurs in patients without pre-existing hepatic dysfunction 4, 2

The positive HBsAg and anti-HEV IgM are incidental findings rather than primary causes 1, 3:

• The pattern of injury (massive transaminase elevation with coagulopathy) is characteristic of paracetamol toxicity, not HBV or HEV flare 3
• HBV flares rarely reach transaminases "in the thousands" without other precipitants 3
• The HBsAg positivity likely represents chronic inactive hepatitis B, which does not cause acute liver failure with this severity 3
• Patients with chronic liver disease can develop paracetamol toxicity at lower thresholds as a precipitant 3

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Immediate Treatment Protocol

1. ICU Admission and Transplant Center Contact

Admit immediately to ICU and establish contact with liver transplant center within the first hour 1:

• All patients with ALF and any degree of altered mental status warrant ICU admission as deterioration can occur rapidly 1
• Early transfer to transplant center improves outcomes, as 10-29% will require emergent transplantation 1
• This patient meets criteria for potential transplantation with INR 3.2, creatinine elevation, and Grade 2-3 encephalopathy 4, 1, 2

2. N-Acetylcysteine (NAC) Administration - HIGHEST PRIORITY

Initiate IV N-acetylcysteine immediately without delay, regardless of time since ingestion 4, 1, 3, 2:

• NAC should be administered systematically in all ALF patients whatever the suspected aetiology 4
• NAC provides mortality benefit and reduces cerebral edema even when started >24 hours post-ingestion 1, 3, 2
• Standard IV NAC protocol 1, 2, 5:
  • Loading dose: 150 mg/kg IV over 15-60 minutes
  • Second dose: 50 mg/kg IV over 4 hours
  • Third dose: 100 mg/kg IV over 16 hours
  • Continue NAC until transaminases are declining and INR normalizes 2

3. Hepatic Encephalopathy Management

Monitor encephalopathy grade frequently and prepare for intubation 4, 1:

• Intubate and sedate if GCS <8 or Grade III-IV encephalopathy develops 4, 1
• Maintain serum sodium between 140-145 mmol/L to prevent cerebral edema 4, 1
• Do NOT use lactulose or rifaximin - these are contraindicated in ALF 4, 1
• Do NOT use benzodiazepines or metoclopramide 4
• Monitor arterial ammonia levels - sustained levels 150-200 mmol/L increase risk of intracranial hypertension 4

4. Acute Kidney Injury Management

Initiate continuous renal replacement therapy (CRRT) for AKI 4, 1:

• CRRT is preferred over intermittent hemodialysis in ALF 1
• High-dose hemofiltration helps reduce ammonia levels 6
• Avoid nephrotoxic drugs including NSAIDs 4, 1
• Fluid resuscitation with crystalloids as first-line therapy 4, 1

5. Hemodynamic Support

Maintain mean arterial pressure ≥50-60 mmHg 1:

• Aggressive fluid resuscitation with crystalloid fluids as first choice 4, 1
• Norepinephrine infusion for refractory hypotension (current BP 100/60 mmHg is borderline) 4, 1
• Assess volume status, cardiac output, and cardiac function with echocardiography 4

6. Coagulopathy Management

Do NOT routinely correct coagulation parameters 4, 1:

• INR and PT are essential prognostic markers and should not be routinely corrected 1
• Restrict clotting factor administration to cases of active bleeding only 4, 1
• No prophylactic FFP or vitamin K unless active hemorrhage occurs 1

7. Metabolic Monitoring

Monitor blood glucose at least every 2 hours 4, 1:

• Maintain normoglycemia with continuous glucose infusions 1
• Hypoglycemia symptoms may be obscured by encephalopathy 1
• Provide 60 grams of protein daily via enteral nutrition when possible 1

8. Infection Surveillance

Administer empirical broad-spectrum antibiotics immediately 4, 1:

• This patient has worsening encephalopathy, meeting criteria for empirical antibiotics 4, 1
• Infection is the most common precipitant of deterioration in ALF 1
• Perform blood and urine cultures before antibiotic administration 4

9. Stress Ulcer Prophylaxis

Initiate stress ulcer prophylaxis 4:

• Standard recommendations for critically ill patients apply 4
• No history of hematemesis or melena currently, but prophylaxis is indicated 4

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Addressing the Viral Hepatitis Co-infections

Hepatitis B Management

Do NOT initiate antiviral therapy for HBV at this time 3:

• The acute presentation requires NAC first; antiviral therapy can be addressed after stabilization 3
• Entecavir is indicated for chronic hepatitis B management, not acute hepatotoxicity 3
• HBsAg positivity likely represents chronic inactive HBV, which is not the primary cause of this ALF 3

Hepatitis E Management

No specific antiviral therapy indicated for HEV 4:

• Anti-HEV IgM positivity may represent recent exposure but is not the primary driver of this fulminant presentation 4
• HEV typically causes self-limited hepatitis; this severity is consistent with paracetamol toxicity 4

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Transplant Evaluation Criteria

This patient meets King's College Hospital criteria for potential liver transplantation 4, 1, 2:

• INR >3.0 (actual 3.2) with Grade 2-3 encephalopathy and acute kidney injury 1, 2
• Arterial pH should be checked after adequate resuscitation - if <7.3, this is an absolute indication for transplant listing 4, 1, 2
• Alternative criteria: PT >100 seconds with creatinine >300 μmol/L (>3.4 mg/dL) in Grade III-IV encephalopathy 1, 2

Post-transplant survival for paracetamol-induced ALF 2:

• 1-year survival: 76.7%
• 5-year survival: 66%
• Overall 2-year survival with transplantation: 90% 4

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Critical Pitfalls to Avoid

• Never delay NAC administration - start immediately without waiting for acetaminophen levels 1, 3, 2
• Never use lactulose or rifaximin in ALF - these are contraindicated 4, 1
• Never routinely correct coagulation without active bleeding - INR is a prognostic marker 4, 1
• Never delay transplant center contact - early contact is mandatory for all serious ALF 4, 1
• Never use nephrotoxic agents including NSAIDs in the setting of AKI 4, 1
• Never attribute this presentation primarily to HBV or HEV - the pattern is classic for paracetamol toxicity 1, 3

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Prognosis

With aggressive critical care and NAC therapy, prognosis can be favorable 6, 7:

• Spontaneous mortality rate for paracetamol-induced ALF ranges from 32-50% without transplant 7
• With NAC and supportive care, 90% survival is achievable in paracetamol-induced ALF without transplantation 4
• Hepatic encephalopathy is the key prognostic indicator - short-term transplant-free survival is 52% with Grade 1-2 HE versus 33% with Grade 3-4 HE 4