Liver Failure[edit | edit source]

Introduction[edit | edit source]

Liver failure represents a severe decline in hepatic function that results from the loss of hepatocyte mass and disruption of the liver’s metabolic, synthetic, and detoxifying roles. The condition may develop rapidly, known as acute liver failure, or evolve slowly over months to years, termed chronic liver failure. Because the liver is essential for detoxifying ammonia, metabolizing nutrients, synthesizing clotting factors, and producing bile, its failure leads to multisystem dysfunction. Clinically, liver failure manifests with jaundice, coagulopathy, hepatic encephalopathy, circulatory collapse, renal impairment, and metabolic disturbances. Understanding its pathophysiology requires an integrated view of hepatocellular injury, portal hypertension, systemic inflammatory responses, and compensatory mechanisms.

Causes of Liver Failure[edit | edit source]

Acute liver failure most commonly results from acetaminophen toxicity, acute viral hepatitis, drug-induced liver injury, ischemic hepatitis, autoimmune hepatitis, Wilson disease, and toxins such as Amanita phalloides. Chronic liver failure is typically the result of long-standing hepatic inflammation and fibrosis, as seen in alcoholic liver disease, chronic hepatitis B or C, non-alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson disease, and cholestatic disorders such as primary biliary cholangitis or primary sclerosing cholangitis.

Although the underlying etiologies differ, each pathway ultimately converges on the destruction of hepatocytes and the architectural distortion of the liver, impairing both function and blood flow.

Pathophysiology[edit | edit source]

Liver failure affects virtually all organ systems because the healthy liver performs detoxification, metabolic processing of nutrients, and synthesis of proteins. Loss of these functions leads to a cascade of harmful events.

One of the most important mechanisms is the accumulation of ammonia. Healthy hepatocytes convert ammonia into urea through the urea cycle. When this capacity is lost, ammonia accumulates in the bloodstream, crosses the blood–brain barrier, and enters astrocytes, where it is converted into glutamine. Glutamine increases osmotic pressure within astrocytes, causing cellular swelling and cerebral edema, the hallmark of hepatic encephalopathy.

Another major disturbance involves bilirubin metabolism. Damaged hepatocytes cannot efficiently conjugate or excrete bilirubin, resulting in mixed hyperbilirubinemia and clinically visible jaundice. At the same time, impaired bile secretion causes cholestasis, pruritus, fat malabsorption, and deficiencies of fat-soluble vitamins, particularly vitamin K.

The liver also synthesizes clotting factors II, VII, IX, and X, as well as protein C and protein S. In liver failure, synthesis of these proteins decreases, and simultaneous cholestasis reduces vitamin K absorption. These defects together produce coagulopathy, demonstrated by elevated INR and risk of bleeding.

In chronic liver failure, progressive fibrosis increases resistance to portal blood flow, leading to portal hypertension. Portal hypertension contributes to ascites, splenomegaly, esophageal varices, and renal vasoconstriction, ultimately predisposing patients to hepatorenal syndrome, a functional renal failure characterized by intense renal vasoconstriction and sodium retention.

Systemically, liver failure is associated with inflammation, oxidative stress, and circulatory collapse. Vasodilation and reduced effective arterial blood volume contribute to hypotension, hyponatremia, and reduced renal perfusion. Metabolic complications such as hypoglycemia occur due to loss of gluconeogenesis and glycogen storage. Endocrine disturbances such as gynecomastia and spider angiomas result from impaired hormone metabolism.

Clinical Manifestations[edit | edit source]

Liver failure presents with jaundice, dark urine, pale stools, ascites, peripheral edema, and features of portal hypertension.

Patients may exhibit confusion, personality changes, asterixis, or coma due to hepatic encephalopathy. Other findings include easy bruising, bleeding, coagulopathy, hypotension, hypoglycemia, muscle wasting, and signs of systemic infection. In acute liver failure, rapid cerebral edema may develop and represents one of the leading causes of mortality.

Laboratory Findings and Diagnosis[edit | edit source]

Diagnosis relies on a combination of laboratory abnormalities and imaging. Elevated AST and ALT levels indicate hepatocellular injury, while markedly increased INR reflects impaired synthesis of clotting factors. Hyperbilirubinemia is typical, with both conjugated and unconjugated fractions elevated. Serum albumin is often low in chronic failure, and ammonia levels rise in encephalopathy. Thrombocytopenia may occur due to splenic sequestration in portal hypertension. Imaging techniques such as ultrasound or CT can demonstrate cirrhosis, ascites, biliary obstruction, or vascular complications. Additional tests—including viral serologies, autoimmune markers, acetaminophen level, and copper studies—help identify the underlying cause.

Management[edit | edit source]

Management depends on whether the failure is acute or chronic. Acute liver failure is a medical emergency requiring intensive care, airway protection, treatment of the underlying cause (such as N-acetylcysteine for acetaminophen toxicity), correction of coagulopathy, management of cerebral edema, and early evaluation for liver transplantation. Chronic liver failure focuses on addressing the underlying disease (such as antiviral therapy or alcohol cessation), controlling complications of portal hypertension, preventing infection, treating hepatic encephalopathy with lactulose and rifaximin, and managing ascites with diuretics and paracentesis. Ultimately, liver transplantation may be necessary when medical therapy fails to maintain adequate function.

Summary[edit | edit source]

Liver failure represents a severe impairment of essential hepatic functions and occurs as either acute or chronic disease. Its pathophysiology includes accumulation of toxic metabolites such as ammonia, loss of synthetic capacity, cholestasis, and the hemodynamic consequences of portal hypertension. Clinical manifestations range from jaundice and coagulopathy to encephalopathy, renal dysfunction, and circulatory collapse. Prompt recognition and treatment of the underlying cause, management of complications, and timely evaluation for liver transplantation are essential for improving survival.