2025 PACUPrep BCCCP Preparatory Course Acute Liver Failure Diagnostic Criteria and Severity Stratification in Acute Liver Failure
Diagnostic Criteria and Severity Stratification in Acute Liver Failure

Diagnostic Criteria and Severity Stratification in Acute Liver Failure

Objectives Icon A crosshair target symbol, representing a clinical objective.

Objective

Accurate diagnosis and risk stratification in acute liver failure (ALF) guide all downstream management—from targeted pharmacotherapy to timely transplant referral.

1. Clinical & Laboratory Diagnostic Framework

ALF is defined by acute hepatocellular injury with coagulopathy (INR ≥1.5) and any degree of hepatic encephalopathy (HE) in patients without prior chronic liver disease. Early recognition via focused history, exam, and labs is paramount.

Diagnostic Triad

  • Acute onset of liver injury, typically with markedly elevated aminotransferases (AST/ALT).
  • Severe synthetic dysfunction, defined as an INR ≥1.5 that is not responsive to vitamin K administration.
  • Presence of any grade of hepatic encephalopathy (HE), ranging from mild confusion to coma (West-Haven Grade I–IV).

Initial Laboratory Panel

  • Liver Function Tests: AST, ALT (often >1,000 IU/L in acetaminophen-induced ALF), total and direct bilirubin.
  • Coagulation Studies: PT/INR, fibrinogen (a level <100 mg/dL signals severe synthetic failure), and D-dimer.
  • Metabolic and Renal Function: Serum ammonia (levels >150 µmol/L predict a high risk of cerebral edema), electrolytes, BUN, and creatinine to detect acute kidney injury (AKI).
  • Etiologic Workup:
    • Viral Serologies: Hepatitis A, B, C, E (especially in pregnant patients), and Herpes Simplex Virus (HSV).
    • Toxicology Screen: Serum acetaminophen level (mandatory in all patients), and a broader screen for other potential hepatotoxins.
    • Autoimmune Markers: Antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and quantitative immunoglobulins (IgG).
    • Specialized Tests: Consider Wilson disease (serum ceruloplasmin, Kayser-Fleischer rings on exam) in patients under 40 years old.
Pearl Icon A shield with an exclamation mark, indicating a clinical pearl. Clinical Pearls
  • The presence of hepatic encephalopathy is the key feature that distinguishes ALF from severe acute hepatitis or acute-on-chronic liver failure.
  • Perform serial mental status examinations (e.g., every 4–6 hours) to detect subtle progression of HE, which can rapidly escalate.

2. Imaging Evaluation

Imaging plays a crucial role in excluding vascular or biliary etiologies that can mimic ALF and helps identify potential complications of severe liver disease or hepatic encephalopathy.

Abdominal Ultrasound with Doppler

This is the initial imaging modality of choice. It is used to assess:

  • Vascular Patency: Doppler flow in the hepatic artery, portal vein, and hepatic veins is essential to rule out acute Budd–Chiari syndrome or portal vein thrombosis.
  • Biliary Tree: Evaluates for biliary obstruction from stones or strictures, which can cause severe liver injury but is not true ALF.

CT / MRI

  • Contrast-Enhanced Studies: Useful for clarifying vascular anatomy or identifying focal lesions when ultrasound is inconclusive.
  • MRI: Offers superior soft-tissue detail of the liver parenchyma but is often limited by the patient’s clinical instability and inability to remain still.

Neuroimaging (Noncontrast Head CT)

This is not a routine test but is indicated for any patient with an acute worsening of HE or new focal neurologic deficits. Its primary purpose is to exclude intracranial hemorrhage or ischemic stroke before attributing the change in mental status solely to cerebral edema from ALF.

Pearl IconA shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl

In patients with concurrent acute kidney injury (AKI), contrast-enhanced ultrasound (CEUS) can be a valuable tool to assess liver perfusion without exposing the patient to potentially nephrotoxic iodinated contrast agents used in CT scans.

3. Role of Liver Biopsy

Liver biopsy is reserved for select cases of ALF where the etiology remains indeterminate after a comprehensive noninvasive workup. The procedure carries a significant bleeding risk due to coagulopathy.

Indications

  • Etiology remains unclear after extensive laboratory and imaging evaluation.
  • High suspicion for autoimmune hepatitis (AIH) or an infiltrative disease (e.g., malignancy) where histologic confirmation would directly alter management.

Transjugular Technique

This is the preferred approach in ALF. Access is gained via the internal jugular vein, allowing the biopsy needle to be passed into the hepatic veins. This technique significantly reduces the risk of intraperitoneal hemorrhage compared to a percutaneous approach. A sample containing at least 11 portal tracts is considered adequate for diagnosis.

Impact on Management

  • Confirms Autoimmune Hepatitis: The presence of interface hepatitis on histology would prompt the initiation of corticosteroids.
  • Identifies Other Causes: Can reveal unexpected diagnoses like lymphoma, metastatic cancer, or other infiltrative processes.
Pearl IconA shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl

A liver biopsy should only be performed if the results are expected to change immediate clinical management. It should not delay the initiation of empiric therapies (like N-acetylcysteine) or referral for liver transplantation.

4. Severity Classification Systems

Grading the severity of hepatic encephalopathy and using validated prognostic scores are essential for predicting outcomes, guiding ICU triage, and determining the urgency of referral for liver transplantation.

West-Haven Criteria for Hepatic Encephalopathy (HE)

  • Grade I: Mild confusion, euphoria or anxiety, shortened attention span.
  • Grade II: Lethargy, disorientation, obvious personality change, asterixis present.
  • Grade III: Somnolent but arousable, gross disorientation, incoherent speech.
  • Grade IV: Coma, unresponsive to pain.

Prognostic Scoring Systems

The King’s College Criteria (KCC) and the Model for End-Stage Liver Disease (MELD) score are the two most widely used systems to predict spontaneous survival and identify candidates for urgent transplantation.

Prognostic Scores in Acute Liver Failure
System Etiology Criteria for Poor Prognosis (Transplant Indicated)
King’s College Criteria (KCC) Acetaminophen Arterial pH < 7.30 OR all three of the following:
  • INR > 6.5
  • Serum Creatinine > 3.4 mg/dL (>300 µmol/L)
  • Grade III–IV HE
King’s College Criteria (KCC) Non-Acetaminophen INR > 6.5 OR any three of the following five:
  • Age < 10 or > 40 years
  • Jaundice to encephalopathy time > 7 days
  • INR > 3.5
  • Serum Bilirubin > 17.5 mg/dL (>300 µmol/L)
  • Unfavorable etiology (e.g., indeterminate, drug-induced)
MELD / MELD-Na All Etiologies A MELD score > 30.5 is associated with high short-term mortality. It is calculated using bilirubin, INR, and creatinine (plus sodium for MELD-Na). It is highly sensitive for predicting mortality but less specific than KCC for transplant need.
Pearl IconA shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl

For optimal decision-making, many centers use a combined approach: the high sensitivity of the MELD score to identify at-risk patients early, and the high specificity of the King’s College Criteria to confirm the need for urgent transplant listing.

5. Integration into Management Pathway

A structured approach that integrates diagnostic findings with severity stratification is critical for timely and appropriate management, including ICU admission, monitoring frequency, and transplant evaluation.

ALF Management Pathway A flowchart showing the clinical pathway for a patient with suspected Acute Liver Failure. It starts with initial assessment, moves to ICU admission based on HE grade, then to prognostic scoring, which triggers transplant center notification and ongoing intensive monitoring. 1. Suspected ALF Check Triad: Injury, INR ≥1.5, any HE 2. ICU Admission Grade II-IV HE? Other organ failure? 3. Calculate Prognostic Scores KCC or MELD >30.5 met? → NOTIFY TRANSPLANT CENTER 4. Intensive Monitoring Serial Labs (INR, NH3) Neuro Checks q4-6h Re-assess scores daily
Figure 1: Integrated Management Pathway for Acute Liver Failure. This pathway highlights key decision points, from initial diagnosis and ICU triage to prognostic scoring, which prompts timely notification of a transplant center and guides the cadence of intensive monitoring.
Pearl IconA shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl

Prognostic scores are not static; they must be reassessed serially (e.g., daily). A patient’s trajectory—whether improving or deteriorating—is often more informative than a single score. Early communication with a transplant center is crucial, even if the patient does not immediately meet criteria, to facilitate a smooth and rapid transfer if needed.

References

  1. Shingina A, Mukhtar N, Wakim-Fleming J, et al. Acute liver failure guidelines. Am J Gastroenterol. 2023;118(7):1128–1153.
  2. Keegan MT. How do I manage a patient with acute liver failure? In: Elsevier; 2025:500–513.
  3. Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy practice guideline. Hepatology. 2014;60(2):715–735.
  4. Flamm SL, Yang Y-X, Singh S, Falck-Ytter YT; AGA Institute. AGA guideline ALF. Gastroenterology. 2017;152(3):644–647.
  5. O’Grady JG, Alexander GJ, Hayllar KM, Williams R. Early prognosis in fulminant hepatic failure. Gastroenterology. 1989;97(2):439–445.
  6. McPhail MJW, Farne H, Senvar N, et al. KCC vs MELD in ALF meta-analysis. Clin Gastroenterol Hepatol. 2016;14(4):516–525.
  7. Lee WM, Squires RH Jr, Nyberg SL, et al. Transjugular liver biopsy safety. Hepatology. 2008;47(4):1401–1415.
  8. Herrine SK, Moayyedi P, Brown RS Jr, et al. AGA technical review on ALF. Gastroenterology. 2017;152(3):648–664.
  9. Lee WM, Hynan LS, Rossaro L, et al. IV NAC in non-APAP ALF. Gastroenterology. 2009;137(3):856–864.
Previous Topic
Back to Lesson
Next Topic