Hepatic FailureEdit
Hepatic failure is a life-threatening syndrome characterized by rapid deterioration of liver function, often presenting with coagulopathy and hepatic encephalopathy. It encompasses several clinical scenarios, most notably acute liver failure (ALF), which occurs in a previously healthy liver, and acute-on-chronic liver failure (ACLF), which develops in a patient with existing chronic liver disease. The liver’s central role in metabolism, detoxification, and synthetic function means that hepatic failure reverberates through virtually every organ system, requiring urgent assessment and multidisciplinary management. For broader context, the liver is the site of liver metabolism, bile production, and the synthesis of clotting factors, albumin, and many other proteins essential to homeostasis.
Because hepatic failure can arise from a wide range of causes, its evaluation centers on rapidly identifying and treating the underlying trigger while supporting organ systems. This article outlines definitions, common etiologies, clinical features, diagnostic approaches, treatment strategies, and the policy and clinical debates that surround the management of this critical condition.
Definition and classification
- Acute liver failure (ALF) is defined by rapid onset of liver dysfunction with coagulopathy (often an international normalized ratio, INR, of 1.5 or higher) and hepatic encephalopathy within weeks, typically without prior cirrhosis. See acute liver failure.
- Acute-on-chronic liver failure (ACLF) describes an acute deterioration in a patient with preexisting chronic liver disease, resulting in multi-organ failure and high short-term mortality. See acute-on-chronic liver failure.
- Other related terms include fulminant hepatic failure and toxin-induced liver failure, which are discussed in the context of specific etiologies below.
Etiology and pathophysiology
Hepatic failure arises from diverse causes that disrupt hepatocyte function, hepatic microcirculation, and biliary flow. Major categories include: - Drug-induced and toxin-related injury, with acetaminophen overdose being a leading cause in many populations. See drug-induced liver injury and acetaminophen. - Viral hepatitis (e.g., hepatitis B and other hepatotropic viruses) leading to rapid hepatic injury in susceptible individuals. - Autoimmune and metabolic disorders, including autoimmune hepatitis and metabolic diseases such as Wilson disease. - Pregnancy-associated liver disease (e.g., acute fatty liver of pregnancy, HELLP syndrome) and toxin exposure from environmental sources or mushrooms. - Ischemic or septic injury resulting from shock, hypotension, or systemic infection, sometimes labeled ischemic hepatitis or hypoxic hepatitis. - Chronic liver disease exacerbations that precipitate ACLF, including decompensation of cirrhosis with superimposed insults.
Pathophysiology commonly involves massive hepatocyte death or dysfunction, loss of synthetic capability (e.g., reduced clotting factor production leading to coagulopathy), impaired bile production, and accumulation of toxins such as ammonia. The systemic consequences can include cerebral edema, renal dysfunction, circulatory instability, infection, and multiorgan failure. See liver and hepatic encephalopathy for related concepts.
Clinical presentation and evaluation
Patients with hepatic failure typically present with rapid changes in mental status, jaundice, and signs of impaired liver synthetic function. Common features include: - Jaundice and dark urine from conjugated hyperbilirubinemia. - Coagulopathy with elevated INR and dependent bleeding risk. - Hepatic encephalopathy ranging from subtle cognitive changes to confusion, stupor, or coma. - Nausea, abdominal pain, tender hepatomegaly, or ascites in some cases. - Systemic signs of infection or organ dysfunction as failure progresses.
Diagnostic evaluation emphasizes rapid etiologic assessment and organ support: - Initial labs: liver enzymes (AST, ALT), bilirubin, INR, albumin, creatinine, electrolytes, and renal function. - Specific etiologies: acetaminophen level when overdose is suspected; serologies for viral hepatitis; autoimmune markers; ferritin and transferrin saturation; ceruloplasmin for suspected Wilson disease. - Imaging: abdominal ultrasound with Doppler to assess hepatic vasculature and biliary tree; cross-sectional imaging as indicated. - Exclusion of biliary obstruction and other reversible causes is essential, and management often proceeds in parallel with diagnostic testing.
See jaundice, coagulopathy, hepatic encephalopathy, ultrasound (with Doppler), and liver for related background.
Management and treatment
Management of hepatic failure is urgent and multidisciplinary, focusing on three aims: treat the underlying cause, prevent or mitigate organ dysfunction, and evaluate for definitive therapies such as liver transplantation when appropriate.
Key components: - Treat reversible etiologies promptly, such as acetaminophen overdose with N-acetylcysteine, or autoimmune hepatitis with immunosuppression where indicated. See acetaminophen and autoimmune hepatitis. - Supportive care in an intensive care setting, including airway protection, hemodynamic support, and meticulous fluid balance. - Management of cerebral edema and intracranial hypertension using appropriate neuromonitoring, head elevation, and, in severe cases, osmotic therapies or invasive monitoring. - Correction of coagulopathy is approached carefully; vitamin K and balanced transfusion strategies may be used, but invasive procedures carry bleeding risks in the setting of coagulopathy. - Infections surveillance and prompt treatment, given high susceptibility to sepsis. - Encephalopathy-directed therapies such as lactulose and, when indicated, antibiotics like rifaximin to reduce gut-derived toxins. - Renal support when indicated; ACLF and ALF patients may develop renal dysfunction that evolves toward hepatorenal syndrome without careful management. - Definitive therapy via liver transplantation is considered when prognosis without transplantation is poor. Transplant candidacy and listing criteria are determined by centers and allocation systems, balancing urgency, likelihood of benefit, and donor organ availability. See liver transplantation and hepatorenal syndrome.
Contemporary debates in management include the role of extracorporeal liver support devices in bridging patients to transplant and the thresholds for listing in various etiologies. See also discussions under drug-induced liver injury and liver transplantation.
Prognosis and outcomes
Prognosis depends on etiology, rapidity of presentation, degree of multi-organ involvement, and access to timely liver transplantation. Early recognition and aggressive management improve survival, but ALF and ACLF can progress rapidly despite optimal care. Prognostic models combine clinical parameters with laboratory data to guide decisions about transplant referral and level of care. See prognosis and liver transplantation for related considerations.
Controversies and policy considerations
While the clinical approach centers on biology and critical care, the broader system context can influence outcomes: - Organ allocation and transplant eligibility criteria shape access to life-saving therapy. Debates focus on balancing urgency against likelihood of benefit, and on optimizing organ utilization. See liver transplantation. - Public health and prevention strategies—such as vaccination programs for hepatitis B, monitoring of prescription medications, and education about safe medication practices—affect incidence and severity of hepatic failure. See hepatitis, drug-induced liver injury. - High-cost therapies and bridging strategies (e.g., extracorporeal support) raise questions about cost-effectiveness and equitable access across health systems. See extracorporeal support discussions in liver support. - The interaction of liver disease with other health priorities—acute care capacity, hospital resources, and long-term management of chronic liver conditions—produces ongoing policy debates about funding and access to multidisciplinary care. See healthcare policy and public health.