Definition of Acute Liver Failure
Acute liver failure (ALF) is defined as the development of rapidly progressive hepatocellular dysfunction with coagulopathy (prothrombin time ratio <50% or INR ≥1.5) and hepatic encephalopathy occurring in patients without any preexisting liver disease, with symptom onset in less than 26 weeks. 1
Core Diagnostic Components
The essential elements that must be present for ALF diagnosis include:
Absence of preexisting liver disease - This is the fundamental distinguishing feature that separates ALF from acute-on-chronic liver failure (ACLF) 1, 2
Coagulopathy - Defined as INR ≥1.5 or prothrombin time ratio <50%, reflecting severe hepatic synthetic dysfunction 1, 3
Rapid deterioration - Symptom onset occurring within 26 weeks, distinguishing it from chronic liver disease 1
Hepatic encephalopathy - While coagulopathy must be present, encephalopathy may be less pronounced in some presentations 2, 3
Severity Classification
ALF can be further stratified based on severity:
Severe ALF - Prothrombin time ratio <50% without encephalopathy 1
Serious ALF (also termed "fulminant hepatitis") - Prothrombin time ratio <50% combined with hepatic encephalopathy 1
The term "fulminant hepatitis" specifically refers to encephalopathy developing within 15 days of jaundice onset, though this terminology is often used interchangeably with serious ALF 1
Key Distinguishing Features from Other Liver Failure Syndromes
It is critical to differentiate ALF from acute-on-chronic liver failure (ACLF), as management and prognosis differ substantially:
ALF occurs in patients with no prior liver disease history 1, 2
ACLF represents acute decompensation in patients with preexisting chronic liver disease or cirrhosis, associated with extrahepatic organ failures 1, 4
Type B hepatic failure involves portosystemic shunting without intrinsic liver disease 5
Type C hepatic failure encompasses cirrhosis-related complications 5
Epidemiology and Clinical Context
ALF is a rare condition, occurring in fewer than 10 cases per million persons annually in developed countries 1. Despite its rarity, it carries significant mortality risk, though prognosis has improved with modern intensive care and liver transplantation, achieving approximately 90% two-year survival rates in transplanted patients and similar rates for acetaminophen-induced ALF managed without transplantation 1.
Common Pitfalls to Avoid
Do not diagnose ALF in patients with known cirrhosis or chronic liver disease - these patients have ACLF by definition, even if previously compensated 1, 4
Do not confuse isolated coagulopathy without encephalopathy as excluding ALF - severe ALF can exist without encephalopathy, though serious ALF requires both 1
Do not overlook undiagnosed chronic conditions - some chronic diseases like autoimmune hepatitis or Wilson's disease may present initially as apparent "ALF" 3