What are the clinical manifestations of fulminant hepatitis?

Clinical Manifestations of Fulminant Hepatitis

Fulminant hepatitis presents with the hallmark combination of coagulopathy (INR ≥1.5) and any degree of mental status alteration (hepatic encephalopathy) in a previously healthy patient, developing within 26 weeks of illness onset. 1

Core Diagnostic Features

Coagulopathy is the defining laboratory abnormality:

• INR >1.5 or prothrombin time prolonged by 4–6 seconds beyond normal 1
• Unresponsive to parenteral vitamin K administration 2
• Reflects severe impairment of hepatic synthetic function 3

Hepatic encephalopathy ranges from subtle confusion to deep coma:

• Any degree of mental alteration establishes the diagnosis when combined with coagulopathy 1
• Progression can occur within days from early confusion to grade 4 coma 4
• Encephalopathy appearing within 7 days of jaundice onset defines "hyperacute" presentation, while 8–28 days defines "acute" presentation 5

Systemic Clinical Manifestations

Jaundice is typically present:

• Develops in >70% of adult patients with acute hepatitis 6
• Serum bilirubin elevation is a key prognostic marker 3

Rapid multiorgan deterioration characterizes the clinical course:

• Progression to renal failure occurs rapidly, particularly in Wilson disease presentations 2
• Hemodynamic instability with hypotension requiring vasopressor support 4
• Cerebral edema develops as encephalopathy worsens, leading to potential cardiovascular collapse 4
• Metabolic acidosis with rising arterial lactate signals impaired tissue perfusion 4

Bleeding complications occur in approximately 10% of patients:

• Most commonly from the upper gastrointestinal tract 4
• Related to severe coagulopathy and thrombocytopenia 4

Etiology-Specific Clinical Patterns

Wilson Disease Fulminant Presentation

This etiology has a highly characteristic pattern that should raise immediate suspicion 2:

• Coombs-negative hemolytic anemia with acute intravascular hemolysis 2, 1
• Paradoxically modest aminotransferase elevations, typically <2,000 IU/L despite fulminant presentation 2, 1
• Markedly subnormal alkaline phosphatase, typically <40 IU/L 2, 1
• Alkaline phosphatase to bilirubin ratio <2 2, 1
• Female predominance with 2:1 female to male ratio 2, 1
• Rapid progression to renal failure 2

Autoimmune Hepatitis Fulminant Presentation

This presentation can be diagnostically challenging 2, 1:

• Normal serum IgG in 25–39% of acute severe cases 1
• Absent or weak ANA in 29–39% of cases 1
• Centrilobular hemorrhagic necrosis with lymphoplasmacytic infiltration on histology 1
• Heterogeneous hypoattenuated areas on CT scan in 65% of cases 1
• May mimic acute viral hepatitis with jaundice and AST levels in the thousands 6

Hepatitis A Fulminant Presentation

• More common in patients >40 years of age 2
• Prodromal symptoms of nausea, anorexia, and lethargy typically improve with jaundice onset 7
• Spontaneous recovery occurs in 30–60% of fulminant cases 2

Laboratory Manifestations

Aminotransferases show variable patterns:

• Typically elevated >2.5 times upper limit of normal 1
• Paradoxically modest elevations (<2,000 IU/L) may indicate worse prognosis, particularly in Wilson disease and late-stage fulminant hepatitis 4
• AST may exceed ALT, potentially reflecting mitochondrial damage 2

Arterial ammonia elevation correlates with encephalopathy severity and cerebral edema risk 4

Metabolic derangements include:

• Hypoglycemia requiring bedside glucose checks every 2 hours 4
• Metabolic acidosis with elevated lactate 4
• Electrolyte disturbances 4

Prognostic Clinical Features

Poor prognostic indicators include 4, 3, 8:

• Age >50 years 2
• Prolonged jaundice (>7 days) before encephalopathy onset 7
• Grade 4 encephalopathy 3
• Persistent arterial lactate elevation 4
• Underlying chronic liver disease (hepatitis B or C) 2

Post-transplant survival for acute liver failure now ranges from 80–90%, reflecting marked improvements in outcomes 4

Critical Pitfalls to Avoid

Do not underestimate severity based on modest aminotransferase elevations—in Wilson disease, ALT may remain <2,000 IU/L despite fulminant presentation requiring urgent transplantation 4, 1

Do not rely on negative autoantibodies to exclude autoimmune hepatitis—up to 39% of acute severe cases lack typical ANA or have normal IgG levels 1, 6

Do not delay ICU transfer or transplant center contact while awaiting complete diagnostic workup—patients can progress to cerebral edema and multiorgan failure within days 4, 1

Recognize that lack of response to vitamin K is part of the diagnostic criteria, not a treatment failure 2