What is liver failure?

Liver failure, also known as hepatic failure, is a life-threatening condition characterized by severe impairment or loss of liver function. It occurs when the liver is unable to perform its essential metabolic, detoxification, and regulatory functions, leading to systemic complications and potentially fatal consequences. Liver failure can be acute (acute liver failure) or chronic (chronic liver failure or end-stage liver disease).


  • Acute Liver Failure (ALF): Acute liver failure is a rapid-onset condition in which liver function deteriorates rapidly over a period of days to weeks. It is often characterized by the sudden onset of symptoms and severe liver dysfunction, leading to hepatic encephalopathy (confusion, altered consciousness) and multi-organ failure. Acute liver failure can result from various causes, including viral hepatitis (such as hepatitis A, B, or E), drug-induced liver injury, autoimmune hepatitis, acute fatty liver of pregnancy, and toxic liver injury (due to ingestion of toxic substances such as acetaminophen).


  • Chronic Liver Failure: Chronic liver failure, also known as end-stage liver disease or end-stage liver failure, is a progressive condition characterized by irreversible damage to liver tissue and a gradual decline in liver function over time. Chronic liver failure typically develops over months to years and may result from chronic liver diseases such as cirrhosis, chronic hepatitis B or C infection, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis, and genetic liver disorders. As liver function deteriorates, individuals with chronic liver failure may experience symptoms such as jaundice (yellowing of the skin and eyes), ascites (fluid accumulation in the abdomen), hepatic encephalopathy (confusion, cognitive impairment), coagulopathy (bleeding disorders), and portal hypertension (increased pressure in the portal vein system).


What is the relationship between liver failure and oxidative stress?

The relationship between liver failure and oxidative stress is complex and multifaceted. Liver failure, whether acute or chronic, is often associated with increased oxidative stress, and oxidative stress, in turn, can contribute to the progression and severity of liver failure. Here’s how they are related:


  • Oxidative Stress in Liver Disease: Liver failure is often preceded or accompanied by various liver diseases, such as viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), cirrhosis, and autoimmune liver diseases. These liver diseases are characterized by chronic inflammation, hepatocellular injury, and hepatocyte death, which can lead to increased production of reactive oxygen species (ROS) and oxidative stress within the liver.


  • Mitochondrial Dysfunction: Liver failure is frequently associated with mitochondrial dysfunction, which can contribute to increased ROS production and oxidative stress. Mitochondria are the primary sites of ROS generation within cells, and impaired mitochondrial function can disrupt electron transport chain activity, leading to the leakage of electrons and the generation of ROS. Mitochondrial dysfunction is commonly observed in liver diseases such as alcoholic liver disease, NAFLD, and cirrhosis, and it can further exacerbate oxidative stress and cellular damage in the liver.


  • Inflammatory Responses: Liver failure is often characterized by chronic inflammation, which plays a critical role in the pathogenesis of liver disease. Inflammatory processes can stimulate the production of ROS by activating immune cells, such as macrophages and neutrophils, and inducing the expression of pro-inflammatory cytokines and chemokines. ROS, in turn, can amplify inflammatory responses by promoting the activation of inflammatory signaling pathways, such as nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1), and exacerbating tissue injury and inflammation.


  • Hepatocyte Injury and Apoptosis: Liver failure is associated with hepatocyte injury and apoptosis (programmed cell death), which can result from various insults, including viral infections, alcohol toxicity, metabolic dysfunction, and immune-mediated damage. Hepatocyte injury and apoptosis can trigger oxidative stress by releasing intracellular contents, such as cytochrome c and reactive oxygen species, into the extracellular environment, leading to the activation of oxidative stress pathways and the generation of ROS.


  • Impaired Antioxidant Defenses: Liver failure is often accompanied by impaired antioxidant defenses, which can further exacerbate oxidative stress and cellular damage. Antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, play crucial roles in neutralizing ROS and protecting cells from oxidative damage. However, in liver failure, the activity of antioxidant enzymes may be compromised due to depletion of antioxidant reserves, impaired gene expression, or oxidative modification of antioxidant proteins, leading to an imbalance between ROS production and antioxidant defenses.


Overall, oxidative stress plays a significant role in the pathogenesis and progression of liver failure by contributing to hepatocyte injury, inflammation, mitochondrial dysfunction, and impaired antioxidant defenses.