Abstract
Abbreviated pathogenesis and clinical course of the acute liver failure syndrome.
The pathogenesis and clinical course of the syndrome of acute liver failure (ALF)
differs depending upon the etiology of the primary liver injury. In turn, the severity
of the liver injury and resulting synthetic failure is often the primary determinant
of whether a patient is referred for emergency liver transplantation. Injuries by
viral etiologies trigger the innate immune system via pathogen-associated molecular
patterns (PAMPs), while toxin-induced (and presumably ischemia-induced) injuries do
so via damage-associated molecular patterns (DAMPs). The course of the clinical syndrome
further depends upon the relative intensity and composition of cytokine release, resulting
in an early proinflammatory phenotype (SIRS) and later compensatory anti-inflammatory
response phenotype (CARS). The outcomes of overwhelming immune activation are the
systemic (extrahepatic) features of ALF (cardiovascular collapse, cerebral edema,
acute kidney injury, respiratory failure, sepsis) which ultimately determine the likelihood
of death.
Acute liver failure (ALF) continues to carry a high risk of mortality or the need
for transplantation despite recent improvements in overall outcomes over the past
two decades. Optimal management begins with identifying that liver failure is indeed
present and its etiology, since outcomes and the need for transplantation vary widely
across the different etiologies. Most causes of ALF can be divided into hyperacute
(ischemia and acetaminophen) and subacute types (other etiologies), based on time
of evolution of signs and symptoms of liver failure; the former evolve in 3 to 4 days
and the latter typically in 2 to 4 weeks. Both involve intense release of cytokines
and hepatocellular contents into the circulation with multiorgan effects/consequences.
Management involves optimizing fluid balance and cardiovascular support, including
the use of continuous renal replacement therapy, vasopressors, and pulmonary ventilation.
Early evaluation for liver transplantation is advised particularly for acetaminophen
toxicity, which evolves so rapidly that delay is likely to lead to death.
Vasopressor support, high-grade hepatic encephalopathy, and unfavorable (subacute)
etiologies heighten the need for urgent listing for liver transplantation. Prognostic
scores such as Kings Criteria, Model for End-Stage Liver Disease, and the Acute Liver
Failure Group prognostic index take these features into account and provide reasonable
but imperfect predictive accuracy. Future treatments may include liver support devices
and/or agents that improve hepatocyte regeneration.
Keywords
encephalopathy - coagulopathy - hepatocyte injury - renal replacement therapy - prognostic
score
