Causes, Diagnosis, and Management of Acute Liver Failure

• Introduction:
  • Acute liver failure (ALF) is a complex critical illness with severe multisystem involvement.
  • ALF predominantly affects young individuals with few comorbidities and has a high mortality.
  • Management challenges include hepatic encephalopathy, cerebral edema, hemostatic abnormalities, hemodynamic instability, metabolic abnormalities, renal failure, and vulnerability to infection.
• Definition:
  • ALF is diagnosed based on the triad of encephalopathy, abnormal measures of hemostasis, and the development of overt liver failure in a short interval.
  • Different classification systems exist to define ALF, with the duration of illness before encephalopathy being strongly associated with underlying etiologies and outcomes.
  • Hyperacute patients have the highest spontaneous survival rate.
• Etiology:
  • The causes of ALF are numerous, with marked variation in etiology across regions.
  • Management and outcomes are influenced by the underlying causes of ALF.
  • Drug-induced liver injury, viral hepatitis, vascular thrombosis, inherited metabolic disorders, and pregnancy-related conditions are some of the causes of ALF.
• Drugs:
  • Acetaminophen overdose is the most common cause of ALF in many countries.
  • Direct hepatotoxicity and idiosyncratic hepatotoxicity are two types of drug-induced liver injury that can cause ALF.
  • Other drugs and toxins can also cause ALF via direct mechanisms.
• Viral Hepatitis:
  • Hepatitis A, B, D, and E viruses are established causes of ALF.
  • Hepatitis C virus rarely results in ALF.
  • Serologic markers are used for the diagnosis of viral hepatitis.
• Diagnosis:
  • Diagnosis of ALF involves clinical evaluation, laboratory tests, and imaging studies.
  • Early detection and prompt treatment are crucial for better outcomes.
• Management:
  • Supportive care and prevention of complications are the mainstay of ALF management.
  • Hepatic regeneration and emergency liver transplantation are potential treatment options.
  • A systematic and coordinated approach is required for effective management of ALF.
• Conclusion:
  • ALF is a rare but life-threatening condition that requires prompt diagnosis and comprehensive management.
  • Further research is needed to improve outcomes and develop targeted therapies for ALF.
• Viral Causes of Acute Liver Failure:
  • Hepatitis E virus (HEV) is a viral cause of acute liver failure (ALF) that is spread via the fecal-oral route.
  • Other nonhepatotropic viruses, particularly Herpesviridae, can also cause ALF, especially when there are specific features of the infective agent.
  • Up to a fifth of ALF cases have no clear cause and may represent unidentified viral pathogens, unusual autoimmune hepatitis manifestations, or unrecognized drug reactions.
• Other Causes of Acute Liver Failure:
  • Ischemic hepatitis can result in ALF if severe shock is present, but hepatic recovery often follows resuscitation and reversal of the primary problem.
  • Autoimmune hepatitis can present as a subacute progression to ALF and may be controlled with corticosteroids.
  • Amanita mushroom poisoning, Wilson disease, Budd-chiari syndrome, acute fatty liver of pregnancy, and Reye syndrome are other causes of ALF.
• Predictive Scoring Systems and Imaging for ALF:
  • Emergency liver transplantation (ELT) is the only intervention proven to improve survival in ALF, but some patients may achieve ELT-free survival with supportive care alone.
  • Several predictive scoring systems exist to differentiate high-risk patients from those who may survive with supportive care alone.
  • Imaging with computed tomography (CT) can assist in prognostic assessment of residual liver volume.
  • Liver biopsy may be safer via a transjugular route and can be diagnostically useful in some cases.
• Clinical Features of Acute Liver Failure:
  • ALF is characterized by constitutional symptoms, derangement in hemostatic parameters, jaundice, and hepatic encephalopathy (HE).
  • Laboratory tests show elevated transaminase levels, bilirubin, hypoglycemia, hyperlactatemia, hyperammonemia, and abnormalities in blood gas analysis.
  • Progressive worsening of INR indicates deterioration, while improvement suggests recovery.
• Management Challenges in Acute Liver Failure:
  • Hepatic encephalopathy is a result of underlying liver failure and requires management.
  • Cerebral edema and intracranial hypertension can occur in ALF and pose additional challenges.
• Cerebral edema and hyperammonemia:
  • Cerebral edema occurs almost exclusively in Acute Liver Failure (ALF)
  • Ammonia accumulation and low blood urea concentrations cause neurotoxicity
• Challenges in detecting neurologic deterioration:
  • Early intracranial hypertension may not be obvious on neuroimaging
  • Monitoring strategies have limitations and haven't improved outcomes
• Hemostatic abnormalities:
  • ALF results in abnormalities of hemostatic parameters
  • Clotting appears deranged, but hemostasis remains intact
  • INR is a poor predictor of bleeding risk, while thrombocytopenia and hypofibrinogenemia are associated with hemorrhage
• Vasodilatory shock and circulatory dysfunction:
  • Vasodilated, hyperdynamic systemic circulation occurs in ALF
  • Fluid resuscitation and vasopressor therapy are recommended
  • Inotropic support may become necessary in advanced circulatory failure
• Metabolic abnormalities:
  • Severe metabolic derangement is a hallmark of ALF
  • Hyperlactatemia and hypoglycemia are serious developments
  • Hyponatremia, hypokalemia, hypophosphatemia, and adrenal insufficiency are possible
• Renal failure and need for CRRT:
  • Acute renal failure occurs commonly in ALF
  • CRRT plays a neuroprotective role by removing toxins