What is the typical time to death in untreated acute liver failure?

Time to Death in Untreated Acute Liver Failure

In untreated severe acute liver failure, death typically occurs within 6 months, with 40% of patients dying within this timeframe, though fulminant presentations can progress to death within 8 weeks of disease onset. 1

Timeframe Based on Severity and Presentation

Fulminant Presentation (Most Rapid)

• Hepatic encephalopathy developing within 8 weeks of jaundice onset defines fulminant liver failure, which represents the most aggressive form with the shortest time to death. 1
• Patients meeting criteria for severe acute liver failure (ACLF-3 with ≥3 organ failures and CLIF-C ACLF score >70) have approximately 90% mortality within 90 days without intervention. 1

Severe Untreated Disease (Standard Progression)

• 40% of patients with untreated severe autoimmune hepatitis die within 6 months of diagnosis, establishing this as the typical mortality window for severe untreated acute liver failure. 1
• Among patients who do not receive transplantation, 26.7% die within 30 days of admission, indicating that a substantial proportion experience very rapid deterioration. 2

Factors Accelerating Time to Death

Laboratory markers predicting early mortality include:

• Sustained aminotransferase levels >10-fold normal, or >5-fold normal with serum γ-globulin ≥2-fold normal 1
• Prothrombin time >25 seconds combined with serum bilirubin >15 mg/dL 3

Histologic findings associated with rapid progression:

• Bridging necrosis or multiacinar necrosis progresses to cirrhosis in 82% within 5 years, with 45% mortality during this period. 1

Etiology-Specific Mortality Timelines

Favorable Prognosis Etiologies (Slower Progression)

• Acetaminophen overdose, hepatitis A, and ischemic injury have approximately 60% spontaneous survival rates, meaning death occurs in 40% but over a more extended timeframe allowing for potential intervention. 4

Poor Prognosis Etiologies (Rapid Progression)

• Drug-induced ALF (non-acetaminophen), hepatitis B, and indeterminate causes have only 25% spontaneous survival, with death occurring more rapidly in the 75% who succumb. 4

Critical Organ Failure Patterns

Multi-organ failure dramatically shortens survival time:

• Patients with NACSELD ACLF (≥2 organ failures) have only 3% 28-day survival, indicating death within one month for 97% of untreated cases. 1, 5
• Persistence of 3-4 non-hematological organ failures at day 3-7 predicts in-hospital mortality with 93-100% specificity. 1
• Patients with 4 or more organ failures at days 3-7 after ACLF-3 diagnosis have 90% mortality at 28 days and 100% mortality at 90 days. 1

Complications Leading to Death

Cirrhosis Development and Sequelae

• Cirrhosis develops in at least 40% of survivors of the initial acute episode. 1
• Among those developing cirrhosis, 54% develop esophageal varices within 2 years. 1
• 20% of individuals with esophageal varices die from hemorrhage, adding another mortality mechanism. 1

Infection-Related Mortality

• Bacterial infection increases mortality approximately fourfold regardless of etiology, and can precipitate rapid decompensation. 5

Important Clinical Caveats

The "transplantation window" is often narrow in acute liver failure, with rapid clinical deterioration making the timeframe for intervention extremely limited. 1 This underscores that even short delays in recognition can result in death within days to weeks rather than months.

Spontaneous survival without transplantation occurs in approximately 45% of adults with acute liver failure overall, but this varies dramatically by etiology and severity. 4 The 55% who die without intervention typically do so within the 6-month window, with the majority dying within 30-90 days based on severity.

In less severe presentations, patients may survive longer but still face grim outcomes: even with less severe laboratory and histologic findings, 10% die from hepatic failure within 15 years. 1 However, this represents chronic progression rather than acute liver failure.