Criteria for Fulminant Hepatitis
Fulminant hepatitis (acute liver failure) is defined by the presence of coagulation abnormality (INR >1.5 or prothrombin time >24 seconds) combined with any degree of mental alteration (hepatic encephalopathy) in a patient without preexisting cirrhosis, with illness duration less than 26 weeks. 1, 2
Core Diagnostic Criteria
The essential elements that must be present include:
- Coagulopathy: International Normalized Ratio (INR) >1.5 or prothrombin time >24 seconds, unresponsive to parenteral vitamin K administration 3, 1, 2
- Hepatic encephalopathy: Any degree of mental status alteration, ranging from subtle confusion to coma 1, 4
- Absence of preexisting cirrhosis: The patient must have been previously healthy without chronic liver disease 1, 4
- Acute timeframe: Symptoms developing within 26 weeks of illness onset 1
A more restrictive classical definition specifies encephalopathy occurring within 15 days of jaundice onset 1.
Specific Clinical Presentations by Etiology
Wilson Disease Fulminant Presentation
When fulminant hepatitis occurs due to Wilson disease, a characteristic pattern emerges that differs from other etiologies 3:
- Coombs-negative hemolytic anemia with acute intravascular hemolysis features 3
- Modest aminotransferase elevations: Typically <2,000 IU/L (much lower than viral or drug-induced causes) 3
- Markedly low alkaline phosphatase: Typically <40 IU/L 3
- Alkaline phosphatase to bilirubin ratio <2 (alkaline phosphatase in IU/L divided by total bilirubin in mg/dL) 3
- Rapid progression to renal failure 3
- Female predominance: 2:1 female to male ratio 3
Autoimmune Hepatitis Fulminant Presentation
The acute severe presentation of autoimmune hepatitis may lack typical chronic features 3:
- Normal serum IgG in 25-39% of cases 3
- Absent or weak ANA in 29-39% of cases 3
- Centrilobular hemorrhagic necrosis with lymphoplasmacytic infiltration on histology 3
- Heterogeneous hypoattenuated areas on unenhanced CT scan in 65% of cases 3
Laboratory Findings
Beyond the mandatory coagulopathy, additional laboratory abnormalities typically include:
- Elevated serum aminotransferases: Usually >2.5 times upper limit of normal, though this varies by etiology 3, 2
- Hyperbilirubinemia: Often marked elevation 2
- Factor V levels: Useful for monitoring progression 5
Prognostic Indicators
Certain features at presentation predict worse outcomes and need for transplantation 2:
- Time to encephalopathy >7 days from first symptom (versus <7 days) 2
- Prothrombin time >55 seconds on admission 2
- Lower ALT levels (≤2,384 IU/L) paradoxically indicate worse prognosis 2
- Higher bilirubin levels on admission 2
Critical Pitfalls to Avoid
The relatively modest aminotransferase elevations in some fulminant cases (particularly Wilson disease) often lead clinicians to underestimate disease severity 3. Do not be falsely reassured by ALT/AST levels that seem "not that high"—the coagulopathy and encephalopathy define the severity, not the transaminases 3, 2.
In acute severe autoimmune hepatitis, the absence of typical autoantibodies and normal IgG levels may delay diagnosis 3. Liver biopsy showing plasmacytic infiltration should prompt consideration of this diagnosis even when serologic markers are negative 3.