Pathophysiology of Acute Liver Failure

Abstract

Acute liver failure (ALF) is a rare syndrome resulting from an acute insult to the liver in patients without known underlying chronic liver disease. It is characterized by loss of synthetic function in the form of jaundice and coagulopathy and development of hepatic encephalopathy. Multiorgan failure (MOF) eventually develops, leading to death. Many different etiologies have been identified, with acetaminophen (APAP) overdose and viral hepatitis being the most common causes worldwide. The pathophysiology of ALF can be divided into cause-specific liver injury pathophysiologies and pathophysiology related to occurrence of secondary MOF. In terms of liver injury pathophysiology, APAP toxicity is the most well known. Secondary MOF is often a result of the initial massive proinflammatory response generating a systemic inflammatory response syndrome followed by a compensatory anti-inflammatory response leading to immune cell dysfunction and sepsis. As the liver is a tremendously important metabolic organ involved in energy metabolism, protein synthesis, fat metabolism, and glycemic control, multiple aspects of nutrition also need to be considered as part of the overall pathophysiology of ALF. (Nutr Clin Pract. 2020;35:24-29)

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

“…APAP-induced hepatotoxicity is a leading cause of hepatic failure involving multiple intracellular events, including mitochondrial damage, oxidative stress, and inflammation ( 41 ). Especially, secondary multiorgan failure, which is caused by APAP toxicity, is often a result of the initial massive proinflammatory response and generates a systemic inflammatory response syndrome ( 42 ). As an inherently inflammatory process, pyroptosis plays vital roles in cellular lysis and proinflammatory cytokine release when hosts defend against infections ( 43 ).…”

Hemoadsorption in ‘Liver Indication’—Analysis of 109 Patients’ Data from the CytoSorb International Registry

“…Extracorporeal hemoadsorption is used by intensive care specialists mostly to prevent or counterbalance the effects of cytokine storm mainly in septic shock and other forms of vasoplegic shock [ 11 ]. Acute forms of liver dysfunction and failure also share the pathophysiological features of dysregulated inflammatory response with sepsis, which serves as the basis of the rationale hemoadsorption in liver dysfunction [ 12 , 13 , 14 ]. There are some case reports, case series, and in vitro data indicating effective removal of bilirubin, bile acids, and ammonia from the blood by using hemoadsorption [ 15 , 16 , 17 , 18 ].…”

Therapeutic plasma exchange in liver failure

“…Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are two distinct classifications of severe hepatic dysfunction associated with secondary multi-organ failures (MOFs), both of which effect significant morbidity and mortality[ 1 - 4 ]. The exact mechanisms by which MOFs are mediated have not been definitively established but are thought to be driven by excessive systemic inflammation and dysregulated immune activation triggered by both microbial and non-microbial factors, and less so by the primary insult to the liver[ 3 , 5 - 7 ].…”