Materiały źródłowe

• #1 Acute liver failure in adults: Management and prognosis – UpToDate

  https://www.uptodate.com/contents/acute-liver-failure-in-adults-management-and-prognosis

  Acute liver failure refers to the development of severe acute liver injury with encephalopathy and impaired synthetic function (international normalized ratio [INR] of ≥1.5) in a patient without cirrhosis or pre-existing liver disease. […] Untreated, the prognosis is poor, so timely recognition and management of patients with acute liver failure is crucial. Whenever possible, patients with acute liver failure should be managed in an intensive care unit (ICU) at a liver transplant center. […] The discussion that follows is largely consistent with society guidelines from the American Association for the Study of Liver Diseases, the American College of Gastroenterology (ACG), and the European Association for the Study of Liver for the management of acute liver failure.

• #2 Acute liver failure – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/1010

  Acute liver failure is a rare, life-threatening, potentially reversible condition defined by jaundice, coagulopathy, and hepatic encephalopathy. […] Treatment involves intensive care unit monitoring, specific therapies based on aetiology, and management of known complications. […] All patients should be considered for possible liver transplantation. […] Prognostic models may be used to assess the probability of spontaneous recovery and are instrumental in selection of patients who should potentially undergo liver transplantation.

• #3 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  The most important aspect of treatment in patients with acute liver failure is to provide good intensive care support. […] Patients with grade II encephalopathy should be transferred to the intensive care unit (ICU) for monitoring. As encephalopathy progresses, protection of the airway becomes increasingly important. […] Most patients with acute liver failure tend to develop some degree of circulatory dysfunction. Careful attention should be paid to fluid management and hemodynamics. […] Monitoring of metabolic parameters, surveillance for infection, maintenance of nutrition, and prompt recognition of gastrointestinal bleeding are crucial. […] Coagulation parameters, complete blood cell count, and metabolic panel should be checked frequently. Serum aminotransferases and bilirubin are generally measured daily to follow the course of the disease.

• #4 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Treatment of Acute Liver Failure […] Supportive measures […] N-Acetylcysteine for acetaminophen toxicity […] Sometimes liver transplantation […] Whenever possible, patients should be treated in an intensive care unit at a center capable of liver transplantation. Patients should be transported as soon as possible because deterioration can be rapid and complications (eg, bleeding, aspiration, worsening shock) become more likely as liver failure progresses. […] Intensive supportive therapy is the mainstay of treatment. Drugs that could worsen manifestations of acute liver failure (eg, hypotension, sedation) should be avoided or used in the lowest possible doses. […] For hypotension and acute kidney injury, the goal of treatment is maximizing tissue perfusion. Treatment includes IV fluids and usually, until sepsis is excluded, empiric antibiotics. If hypotension is refractory to about 20 mL/kg of crystalloid solution, clinicians should consider measuring pulmonary capillary wedge pressure to guide fluid therapy. If hypotension persists despite adequate filling pressures, clinicians should consider using pressors (eg, dopamine, epinephrine, norepinephrine).

• #5 Acute liver failure – Wikipedia

  https://en.wikipedia.org/wiki/Acute_liver_failure

  Liver transplant […] Treatment includes liver transplant. […] Because ALF often involves the rapid deterioration of mental status and the potential for multiorgan failure, patients should be managed in the intensive care unit. […] For patients not at a transplant center, the possibility of rapid progression of ALF makes early consultation with a transplant facility critical. […] Accordingly, plans for transfer to a transplant center should begin in patients with any abnormal mentation. […] Early institution of antidotes or specific therapy may prevent the need for liver transplantation and reduce the likelihood of poor outcome. […] Patients with grade III encephalopathy should be transferred to a liver transplant facility and listed for transplantation. […] The advent of transplantation has changed survival from as low as 15% in the pretransplant era to more than 60% today.

• #6 Acute Liver Failure (ALF) | UCSF Department of Surgery

  https://surgery.ucsf.edu/condition/acute-liver-failure-alf

  Liver transplant can be life saving for patients with severe ALF. Thus, in most cases, patients with ALF should be managed at a medical center that offers liver transplantation as a therapeutic option. […] Survival following liver transplant for ALF has historically been lower than that for chronic liver disease. However, currently one-year survivals of greater than 80% are achieved at many programs, with some larger transplant centers reporting survivals of over 90% for transplanted ALF patients.

• #7 Signs & Symptoms of Liver Failure, Causes, Treatments

  https://my.clevelandclinic.org/health/diseases/17819-liver-failure

  Treatment for liver failure involves: […] Managing its complications. […] Treating the cause, if possible. […] Liver transplantation, if necessary. […] Supportive care to help stabilize your condition might include: […] IV fluids. […] IV nutrition. […] Blood glucose monitoring and supplementation. […] Antibiotics or antivirals. […] Plasma or blood transfusions. […] Oxygen therapy or mechanical ventilation. […] Vasopressor medications to increase blood flow. […] Medications or treatments to stop internal bleeding. […] Dialysis for kidney failure. […] Treatments to address the causes of liver failure might include: […] Treatments for toxic overdose. […] Many toxins that cause acute liver failure have no direct antidote, but acetaminophen poisoning does. […] Its called acetylcysteine.

• #8 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  The most important aspect of treatment in patients with acute liver failure is to provide good intensive care support. […] Patients with grade II encephalopathy should be transferred to the intensive care unit (ICU) for monitoring. As encephalopathy progresses, protection of the airway becomes increasingly important. […] Most patients with acute liver failure tend to develop some degree of circulatory dysfunction. Careful attention should be paid to fluid management and hemodynamics. […] Monitoring of metabolic parameters, surveillance for infection, maintenance of nutrition, and prompt recognition of gastrointestinal bleeding are crucial. […] Coagulation parameters, complete blood cell count, and metabolic panel should be checked frequently. Serum aminotransferases and bilirubin are generally measured daily to follow the course of the disease.

• #9 Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure (Part I) | SCCM

  https://www.sccm.org/clinical-resources/guidelines/guidelines/guidelines-for-the-management-of-adult-acute-and-a

  We recommend against using hydroxyethyl starch for initial fluid resuscitation of patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Moderate […] We suggest against using gelatin solutions for initial fluid resuscitation of patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Low […] We suggest using albumin for resuscitation of patients with acute liver failure or acute on chronic liver failure over other fluids, especially when serum albumin is low (3 mg/dL). Quality of Evidence: Low […] We suggest targeting a mean arterial pressure (MAP) of 65 mm Hg in patients with acute liver failure or acute on chronic liver failure over other fluids, especially when serum albumin is low (3mg/dL), with concomitant assessment of perfusion. Quality of Evidence: Low

• #10 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Treatment of Acute Liver Failure […] Supportive measures […] N-Acetylcysteine for acetaminophen toxicity […] Sometimes liver transplantation […] Whenever possible, patients should be treated in an intensive care unit at a center capable of liver transplantation. Patients should be transported as soon as possible because deterioration can be rapid and complications (eg, bleeding, aspiration, worsening shock) become more likely as liver failure progresses. […] Intensive supportive therapy is the mainstay of treatment. Drugs that could worsen manifestations of acute liver failure (eg, hypotension, sedation) should be avoided or used in the lowest possible doses. […] For hypotension and acute kidney injury, the goal of treatment is maximizing tissue perfusion. Treatment includes IV fluids and usually, until sepsis is excluded, empiric antibiotics. If hypotension is refractory to about 20 mL/kg of crystalloid solution, clinicians should consider measuring pulmonary capillary wedge pressure to guide fluid therapy. If hypotension persists despite adequate filling pressures, clinicians should consider using pressors (eg, dopamine, epinephrine, norepinephrine).

• #11 Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure (Part I) | SCCM

  https://www.sccm.org/clinical-resources/guidelines/guidelines/guidelines-for-the-management-of-adult-acute-and-a

  We suggest placing an arterial catheter for blood pressure monitoring in patients with acute liver failure or acute on chronic liver failure and shock. Quality of Evidence: Low […] We suggest using invasive hemodynamic monitoring to guide therapy in patients with acute liver failure or acute on chronic liver failure and clinically impaired perfusion. Quality of Evidence: Low […] We recommend using norepinephrine as a first-line vasopressor in patients with acute liver failure or acute on chronic liver failure who remain hypotensive despite fluid resuscitation, or those with profound hypotension and tissue hypoperfusion even if fluid resuscitation is ongoing. Quality of Evidence: Moderate […] We suggest adding low-dose vasopressin to norepinephrine in patients with acute liver failure or acute on chronic liver failure who remain hypotensive despite fluid resuscitation to increase blood pressure. Quality of Evidence: Low

• #12 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Patients in the advanced stages of encephalopathy require close follow-up care. Monitoring and management of the hemodynamic and renal parameters, as well as glucose, electrolytes, and acid/base status, become critical. […] In patients with grade III or IV encephalopathy, consider placement of an ICP monitor. […] The primary purpose of ICP monitoring is to detect elevations in ICP and reductions in cerebral perfusion pressure (CPP; calculated as mean arterial pressure [MAP] minus ICP) so that interventions can be made to prevent herniation while preserving brain perfusion. […] ICH is managed initially with the use of mannitol. […] Administration of IV mannitol (in a bolus dose of 0.5-1 g/kg or 50-100 g) is recommended to treat ICH in acute liver failure. […] If life-threatening ICH is not controlled with mannitol infusion and other general management as outlined above, hyperventilation may be instituted temporarily in an attempt to acutely lower the ICP and to prevent impending herniation.

• #13 Signs & Symptoms of Liver Failure, Causes, Treatments

  https://my.clevelandclinic.org/health/diseases/17819-liver-failure

  Treatment for liver failure involves: […] Managing its complications. […] Treating the cause, if possible. […] Liver transplantation, if necessary. […] Supportive care to help stabilize your condition might include: […] IV fluids. […] IV nutrition. […] Blood glucose monitoring and supplementation. […] Antibiotics or antivirals. […] Plasma or blood transfusions. […] Oxygen therapy or mechanical ventilation. […] Vasopressor medications to increase blood flow. […] Medications or treatments to stop internal bleeding. […] Dialysis for kidney failure. […] Treatments to address the causes of liver failure might include: […] Treatments for toxic overdose. […] Many toxins that cause acute liver failure have no direct antidote, but acetaminophen poisoning does. […] Its called acetylcysteine.

• #14 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Electrolyte deficiencies may require supplementation with sodium, potassium, phosphate, or magnesium. […] Hypoglycemia is treated with continuous glucose infusion (eg, 10% dextrose), and blood glucose should be monitored frequently because encephalopathy can mask the symptoms of hypoglycemia. […] Coagulopathy is treated with fresh frozen plasma if bleeding occurs or if an invasive procedure is planned. Fresh frozen plasma is otherwise avoided because it may result in volume overload and worsening of cerebral edema. Also, when fresh frozen plasma is used, clinicians cannot follow changes in international normalized ratio (INR), which are important because INR is an index of severity of acute liver failure and is thus sometimes a criterion for transplantation. Recombinant factor VII is sometimes used instead of or with fresh frozen plasma in patients with volume overload. Its role is evolving. H2 blockers may help prevent gastrointestinal bleeding.

• #15 A guide to managing acute liver failure | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/6/453

  Nearly 2,000 cases of acute liver failure occur each year in the United States. This disease carries a high mortality rate, and early recognition and transfer to a tertiary medical care center with transplant facilities is critical. […] Testing for the cause of acute liver failure needs to start as soon as possible so that specific treatment can be initiated and the patient can be placed on the transplant list if needed. […] Acetylcysteine and either a proton pump inhibitor or a histamine H2 receptor blocker should be given to all patients with acute liver failure. Liver transplant is the cornerstone of therapy in patients not responding to other treatments. […] Many patients with acute liver failure ultimately require orthotopic liver transplant, especially if they present with severe encephalopathy. Other aspects of treatment vary according to the cause of liver failure.

• #16 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Bed rest is recommended. […] Managing fulminant hepatic failure is a team effort. Consultations with specialists in intensive care, gastroenterology, infectious diseases, hematology, neurology, neurosurgery, and transplantation surgery may be needed to address the myriad complex issues that can confront the medical staff. […] As patients with fulminant hepatic failure drift deeper into coma, the ability to protect their airway from aspiration decreases. […] Patients who are in stage III coma should have a nasogastric tube (NGT) inserted for stomach decompression. […] When patients progress to stage III coma, intubation should be performed. […] Short-acting benzodiazepines in low doses (eg, midazolam, 2-3 mg) may be used before intubation, or propofol (50 mcg/kg/min) may be initiated before intubation and continued as an infusion.

• #17 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Nutritional support may be necessary if patients cannot eat. Severe protein restriction is unnecessary; 60 g/day is recommended. […] Acute acetaminophen toxicity is treated with N-acetylcysteine. Because chronic acetaminophen toxicity can be difficult to diagnose, use of N-acetylcysteine should be considered if no cause for acute liver failure is evident. Whether N-acetylcysteine has a slight beneficial effect on patients with acute liver failure due to other conditions is under study. […] Liver transplantation results in average 1-year survival rates of about 84%. Transplantation is thus recommended if prognosis without transplantation is worse. However, prediction is difficult and scores, such as King’s College criteria and the APACHE II (Acute Physiologic Assessment and Chronic Health Evaluation II) score, are not sufficiently sensitive and specific to be used as the only criteria for transplantation; thus, they are used as adjuncts to clinical judgment (eg, based on risk factors).

• #18 Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure (Part I) | SCCM

  https://www.sccm.org/clinical-resources/guidelines/guidelines/guidelines-for-the-management-of-adult-acute-and-a

  We suggest not using branched-chain amino acids (BCAAs) in critically ill patients hospitalized with acute liver failure or acute on chronic liver failure who are tolerating enteral medications. Quality of Evidence: Very Low […] We suggest enteral nutrition (EN) over parenteral nutrition (PN) in critically ill patients hospitalized with acute liver failure or acute on chronic liver failure without contraindication for enteral feeding. Quality of Evidence: Low […] We recommend screening patients with acute liver failure or acute on chronic liver failure for drug-induced causes of liver failure. Drug that are proven or highly suspected to be the cause of acute liver failure or acute on chronic liver failure should be discontinued. […] In patients with acute liver failure or acute on chronic liver failure, we recommend adjusting the doses of medications that undergo hepatic metabolism based on the patients residual hepatic function and using the best available literature. When available, a clinical pharmacist should be consulted.

• #19 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Patients with grade I encephalopathy may sometimes be safely managed in a medicine ward. Frequent mental status checks should be performed, and transfer to an intensive care unit (ICU) is warranted with progression to grade II encephalopathy. […] Sedation should be avoided if possible. Unmanageable agitation may be treated with short-acting benzodiazepines in low doses. […] Patients should be positioned with the head elevated at 30. […] There is increasing evidence that ammonia may play a pathogenic role in the development of cerebral edema. […] Reducing elevated ammonia levels with enteral administration of lactulose might help prevent or treat cerebral edema. […] The occurrence of cerebral edema and intracranial hypertension (ICH) in patients with acute liver failure is related to the severity of encephalopathy.

• #20 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  For encephalopathy, the head of the bed is elevated 30 to reduce risk of aspiration; intubation should be considered early. When selecting drugs and drug doses, clinicians should aim to minimize sedation so that they can monitor the severity of encephalopathy. Propofol is the usual induction drug for intubation because it protects against intracranial hypertension and has a brief duration of action, allowing rapid recovery from sedation. There is no evidence that treatments such as lactulose or rifaximin help alleviate encephalopathy in acute liver failure, although they are useful in portosystemic encephalopathy. […] Measures are taken to avoid increasing intracranial pressure (ICP) and avoid decreasing cerebral perfusion pressure: […] To avoid sudden increases in ICP: Stimuli that could trigger a Valsalva maneuver are avoided (eg, lidocaine is given before endotracheal suctioning to prevent the gag reflex).

• #21 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Patients with grade I encephalopathy may sometimes be safely managed in a medicine ward. Frequent mental status checks should be performed, and transfer to an intensive care unit (ICU) is warranted with progression to grade II encephalopathy. […] Sedation should be avoided if possible. Unmanageable agitation may be treated with short-acting benzodiazepines in low doses. […] Patients should be positioned with the head elevated at 30. […] There is increasing evidence that ammonia may play a pathogenic role in the development of cerebral edema. […] Reducing elevated ammonia levels with enteral administration of lactulose might help prevent or treat cerebral edema. […] The occurrence of cerebral edema and intracranial hypertension (ICH) in patients with acute liver failure is related to the severity of encephalopathy.

• #22 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Bed rest is recommended. […] Managing fulminant hepatic failure is a team effort. Consultations with specialists in intensive care, gastroenterology, infectious diseases, hematology, neurology, neurosurgery, and transplantation surgery may be needed to address the myriad complex issues that can confront the medical staff. […] As patients with fulminant hepatic failure drift deeper into coma, the ability to protect their airway from aspiration decreases. […] Patients who are in stage III coma should have a nasogastric tube (NGT) inserted for stomach decompression. […] When patients progress to stage III coma, intubation should be performed. […] Short-acting benzodiazepines in low doses (eg, midazolam, 2-3 mg) may be used before intubation, or propofol (50 mcg/kg/min) may be initiated before intubation and continued as an infusion.

• #23 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  To temporarily decrease cerebral blood flow: Mannitol (0.5 to 1 g/kg, repeated once or twice as needed) can be given to induce osmotic diuresis, and possibly brief hyperventilation can be used, particularly when herniation is suspected. (However, mannitol is contraindicated with acute kidney injury and serum osmolality must be checked before giving a second dose.) […] To monitor ICP: It is not clear whether or when the risks of ICP monitoring (eg, infection, bleeding) outweigh the benefits of being able to detect cerebral edema early and being able to use ICP to guide fluid and pressor therapy; some experts recommend such monitoring if encephalopathy is severe. However, no data indicate that ICP monitoring impacts mortality. […] Goals of treatment are an ICP of 20 mm Hg and a cerebral perfusion pressure of 50 mm Hg.

• #24 GGC Medicines – Management of Acute Liver Failure

  https://handbook.ggcmedicines.org.uk/guidelines/gastrointestinal-system/management-of-acute-liver-failure/

  Seek senior help early. ITU admission will be required for all grades of encephalopathy in the acute patient. Your consultant should be aware of the patient on the day of admission so that early discussions can take place with relatives and the Scottish Liver Transplant Unit (SLTU), if needed. […] If Grade II or worse on presentation, and cerebral oedema is suspected, nurse the head in a 20 – 300 elevated position and give mannitol IV 20%, 0.5g/kg over 30 – 60 minutes and repeat 4 hourly if necessary. This should not be given outwith a critical care environment. […] Glucose IV 10% at a rate of 100ml/hour. For moderate/severe hypoglycaemia see guideline on Management of Hypoglycaemia. Monitor glucose levels twice daily. […] Do not give blood products (i.e. fresh frozen plasma, factor concentrates) unless bleeding is a problem.

• #25 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Barbiturate agents (thiopental or pentobarbital) may also be considered when severe ICH does not respond to other measures; administration of these drugs has been shown to effectively decrease ICP. […] Moderate hypothermia (32-34C) may prevent or control ICH in patients with acute liver failure. […] Hemodynamic derangements consistent with multiple organ failure occur in acute liver failure. […] In the absence of bleeding, it is usually not necessary to correct clotting abnormalities with fresh frozen plasma (FFP). […] Prothrombin time (PT) and partial thromboplastin time (PTT) become prolonged when plasma coagulation components are diluted to less than 30%, and abnormal bleeding occurs when they are less than 17%. […] Treat acetaminophen (paracetamol, APAP) overdose with N-acetylcysteine (NAC).

• #26 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Barbiturate agents (thiopental or pentobarbital) may also be considered when severe ICH does not respond to other measures; administration of these drugs has been shown to effectively decrease ICP. […] Moderate hypothermia (32-34C) may prevent or control ICH in patients with acute liver failure. […] Hemodynamic derangements consistent with multiple organ failure occur in acute liver failure. […] In the absence of bleeding, it is usually not necessary to correct clotting abnormalities with fresh frozen plasma (FFP). […] Prothrombin time (PT) and partial thromboplastin time (PTT) become prolonged when plasma coagulation components are diluted to less than 30%, and abnormal bleeding occurs when they are less than 17%. […] Treat acetaminophen (paracetamol, APAP) overdose with N-acetylcysteine (NAC).

• #27 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  To reduce cerebral edema: Renal replacement therapy in acute liver failure helps clear ammonia and predicts reduced mortality if initiated early. The European Association for the Study of the Liver (EASL) guidelines on acute liver failure recommend consideration of renal replacement therapy in patients with liver failure and markedly elevated ammonia and/or progressive encephalopathy. […] Seizures are treated with phenytoin; benzodiazepines are avoided or used only in low doses because they cause sedation. […] Infection is treated with antibacterial and/or antifungal drugs; treatment is started as soon as patients show any sign of infection (eg, fever; localizing signs; deterioration of hemodynamics, mental status, or renal function). Because signs of infection overlap with those of acute liver failure, infection is likely to be overtreated pending culture results.

• #28 Acute Liver Failure (ALF) – EMCrit Project

  https://emcrit.org/ibcc/alf/

  Continuous renal replacement therapy initiation when ammonia levels are 150 uM/L may be associated with improved survival. […] Avoid nephrotoxins. Treat electrolyte abnormalities (especially hypokalemia or sodium abnormalities, if they seem to be contributing to encephalopathy). […] Lactulose has not been proven to reduce mortality, but it may decrease ammonia levels and remains a rational therapy (if it can be safely tolerated).

• #29 Acute Liver Failure – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482374/

  The management of ALF consists of supportive care, prevention, and management of complications, specific treatment when the exact etiology is known, and determination of prognosis and the need for liver support including possible liver transplantation. All patients should be hospitalized, preferably at a center which has facilities and expertise for a liver transplant. […] For patients with known or suspected acetaminophen-induced ALF, activated charcoal (if presented within 4 hours of ingestion) and prompt administration of N-acetyl cysteine (NAC) is indicated. […] Patients with hepatitis A and E associated ALF should receive supportive care as no specific anti-virals are known to be effective. […] Patients with identifiable Wilson disease or known hepatic vein thrombosis as the etiology for ALF should be considered for a liver transplant. […] The etiology of ALF and the hospital prognosis could help physicians ascertain whether a particular patient is likely to improve or not, and hence need a liver transplant. […] Liver transplantation, though not readily available is an option for selected patients.

• #30 Acute Liver Failure (ALF) – EMCrit Project

  https://emcrit.org/ibcc/alf/

  Patients with acute hepatic failure can deteriorate rapidly. Especially if the patient is a potential transplant candidate, it is often safest to pursue early transfer to a liver transplant center. […] N-acetylcysteine should be given for both acetaminophen and non-acetaminophen liver failure. Acetaminophen toxicity is the #1 cause of liver failure in many developed nations. This may result from suicide attempts or medication errors (e.g., simultaneous use of several acetaminophen-containing cold medications). […] N-acetylcysteine improves transplant-free survival even in hepatic failure not due to acetaminophen toxicity. […] Consider empiric therapy for hepatorenal syndrome, including albumin and vasopressors. Early initiation of dialysis may assist in ammonia clearance, so this is recommended by the SCCM guidelines and European guidelines.

• #31 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  The protective effect of NAC is greatest when administered within 8 hours of ingestion; however, when indicated, administer NAC regardless of the time since the overdose. […] Liver transplantation is the definitive treatment in liver failure, but a detailed discussion is beyond the scope of this article. […] In selected patients for whom no allograft is immediately available, consider support with a bioartificial liver. […] These modalities permit temporary liver support until a suitable donor liver is found. […] Among the liver support systems currently available, albumin dialysis using the molecular adsorbent recirculating system (MARS) is the one that has been most extensively investigated. […] Patients with acute liver failure are, by necessity, on nothing by mouth (NPO) status.

• #32 Acute Liver Failure (ALF) | UCSF Department of Surgery

  https://surgery.ucsf.edu/condition/acute-liver-failure-alf

  ALF is a medical emergency and requires prompt medical evaluation and treatment. Patients with ALF often require admission to an intensive care unit and are probably best managed in a tertiary referral center that performs liver transplantation, which can be life saving in appropriate candidates. […] The current therapy of ALF is largely supportive. The goal is to anticipate, prevent, and treat complications, and facilitate the patient’s liver regeneration and repair. […] While as of yet there is no proven treatment for the overall ALF condition, an antidote exists for certain causes. […] The most important antidote is N-acetylcysteine (NAC) that is used for acetaminophen poisoning. NAC is highly effective when given within 8-12 hours after acetaminophen overdose, but it loses some of its efficacy thereafter.

• #33 Acute Liver Failure – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482374/

  The management of ALF consists of supportive care, prevention, and management of complications, specific treatment when the exact etiology is known, and determination of prognosis and the need for liver support including possible liver transplantation. All patients should be hospitalized, preferably at a center which has facilities and expertise for a liver transplant. […] For patients with known or suspected acetaminophen-induced ALF, activated charcoal (if presented within 4 hours of ingestion) and prompt administration of N-acetyl cysteine (NAC) is indicated. […] Patients with hepatitis A and E associated ALF should receive supportive care as no specific anti-virals are known to be effective. […] Patients with identifiable Wilson disease or known hepatic vein thrombosis as the etiology for ALF should be considered for a liver transplant. […] The etiology of ALF and the hospital prognosis could help physicians ascertain whether a particular patient is likely to improve or not, and hence need a liver transplant. […] Liver transplantation, though not readily available is an option for selected patients.

• #34 A guide to managing acute liver failure | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/6/453

  Acetylcysteine is the main drug used for acetaminophen toxicity. Ideally, it should be given within 8 hours of acetaminophen ingestion, but giving it later is also useful. […] Patients with hepatitis B-induced acute liver failure should be treated with entecavir or tenofovir. Although this treatment may not change the course of acute liver failure or accelerate the recovery, it can prevent reinfection in the transplanted liver if liver transplant becomes indicated. […] Guidelines advise starting prednisone 40 to 60 mg/day and placing the patient on the liver transplant list. […] Once Wilson disease is suspected, the patient should be listed for liver transplant because death is almost certain without it. […] Although initially used only in patients with acetaminophen-induced liver failure, acetylcysteine has also shown benefit in patients with acute liver failure from other causes.

• #35 Acute Liver Failure: Summary of a Workshop

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3381946/

  Currently, the only effective therapy of ALF is liver transplantation. […] Although a number of prognostic scores have been developed to predict outcome without transplantation, none is considered standard at present. […] Special dilemmas related to ALF management are many: when liver ultrasound suggests cirrhosis, this may be false positive due to a nodular necrotic liver. […] Evidence for efficacy of NAC outside of early acetaminophen poisoning awaits results from the ALF Study Group trial. […] N-acetylcysteine, the standard antidote for acetaminophen overdose, has recently been suggested to be beneficial in other forms of ALF, possibly through its effects on hemodynamics in multiorgan failure and its renal protective actions. […] A prospective, randomized, double-blind, placebo-controlled trial of NAC for cases of ALF not due to acetaminophen has been completed with 173 patients enrolled at 25 study sites, who received placebo or intravenous NAC (Acetadote) over 3 days.

• #36 A guide to managing acute liver failure | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/6/453

  Acetylcysteine is the main drug used for acetaminophen toxicity. Ideally, it should be given within 8 hours of acetaminophen ingestion, but giving it later is also useful. […] Patients with hepatitis B-induced acute liver failure should be treated with entecavir or tenofovir. Although this treatment may not change the course of acute liver failure or accelerate the recovery, it can prevent reinfection in the transplanted liver if liver transplant becomes indicated. […] Guidelines advise starting prednisone 40 to 60 mg/day and placing the patient on the liver transplant list. […] Once Wilson disease is suspected, the patient should be listed for liver transplant because death is almost certain without it. […] Although initially used only in patients with acetaminophen-induced liver failure, acetylcysteine has also shown benefit in patients with acute liver failure from other causes.

• #37

  https://link.springer.com/article/10.1007/s12328-013-0447-1

  Hepatitis B virus (HBV) is the most important cause of acute liver failure (ALF) in Eastern countries. […] Treatment with nucleos(t)ide analogs should be started immediately and should be continued regardless of subgroups of HBV-related ALF. […] Liver transplantation is the only treatment option that improves the prognosis of HBV-related ALF. […] Patients under consideration for transplantation should be given nucleos(t)ide analogs as prophylaxis to reduce the likelihood of post-transplant HBV recurrence. […] The efficacy of antiviral drugs against HBV-related ALF is not directly comparable among studies, because different diagnostic criteria of ALF were used. […] Patients with fulminant and severe acute hepatitis B are indicated for antiviral therapy. […] In severe reactivation of chronic HBV infection, immune activity is already excessive and accompanied with a high level of HBV replication. Thus, oral nucleos(t)ide analogs should be the treatment option.

• #38 Acute Liver Failure – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482374/

  The management of ALF consists of supportive care, prevention, and management of complications, specific treatment when the exact etiology is known, and determination of prognosis and the need for liver support including possible liver transplantation. All patients should be hospitalized, preferably at a center which has facilities and expertise for a liver transplant. […] For patients with known or suspected acetaminophen-induced ALF, activated charcoal (if presented within 4 hours of ingestion) and prompt administration of N-acetyl cysteine (NAC) is indicated. […] Patients with hepatitis A and E associated ALF should receive supportive care as no specific anti-virals are known to be effective. […] Patients with identifiable Wilson disease or known hepatic vein thrombosis as the etiology for ALF should be considered for a liver transplant. […] The etiology of ALF and the hospital prognosis could help physicians ascertain whether a particular patient is likely to improve or not, and hence need a liver transplant. […] Liver transplantation, though not readily available is an option for selected patients.

• #39 Acute Liver Failure: Symptoms, Causes, Diagnosis, Treatment

  https://www.healthline.com/health/acute-liver-failure

  Treatment for acute liver failure depends on the underlying cause. An emergency liver transplant is often required where your liver is replaced with a liver from a donor. […] Supportive treatment for acute liver transplant may include: discontinuing all but essential medications, intravenous (IV) fluids to maintain normal electrolyte levels, other IV medications, blood transfusion for bleeding, proton pump inhibitors (PPIs) to prevent gastrointestinal bleeding, antibiotics if a bacterial cause is suspected, mechanical ventilation to help you breathe. […] If acetaminophen overdose is suspected, you may receive: activated charcoal, N-acetyl cysteine, liver transplant. […] Other potential treatments include: IV methylprednisolone for autoimmune hepatitis, N-acetyl cysteine for some other causes like viral hepatitis, activated charcoal for some types of poisoning, anticoagulation therapy or transjugular intrahepatic portosystemic shunt for Budd-Chiari syndrome, acyclovir for herpes hepatitis or varicella zoster infection.

• #40 A guide to managing acute liver failure | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/6/453

  Acetylcysteine is the main drug used for acetaminophen toxicity. Ideally, it should be given within 8 hours of acetaminophen ingestion, but giving it later is also useful. […] Patients with hepatitis B-induced acute liver failure should be treated with entecavir or tenofovir. Although this treatment may not change the course of acute liver failure or accelerate the recovery, it can prevent reinfection in the transplanted liver if liver transplant becomes indicated. […] Guidelines advise starting prednisone 40 to 60 mg/day and placing the patient on the liver transplant list. […] Once Wilson disease is suspected, the patient should be listed for liver transplant because death is almost certain without it. […] Although initially used only in patients with acetaminophen-induced liver failure, acetylcysteine has also shown benefit in patients with acute liver failure from other causes.

• #41 Management of acute liver failure. Clinical guideline from the Catalan Society of Digestology | Gastroenterología y Hepatología (English Edition)

  https://www.elsevier.es/en-revista-gastroenterologia-hepatologia-english-edition–382-articulo-management-acute-liver-failure-clinical-S2444382419300124

  Immunosuppressive treatment (corticosteroids) can be effective in cases of autoimmune origin if they are administered very early. […] ELT will always be required in ALF due to Wilson’s disease. […] The treatment of hyperthermia could limit the progression of ALF caused by this mechanism (heat stroke or ecstasy intake, often associated with hyperthermia). […] Patients with ALF requiring an ELT should be put on a priority transplant list (grade of evidence III, grade of recommendation 1). […] The artificial and bioartificial liver support systems should be used in the context of controlled clinical trials (grade of evidence II-1, grade of recommendation 1).

• #42 A guide to managing acute liver failure | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/6/453

  Acetylcysteine is the main drug used for acetaminophen toxicity. Ideally, it should be given within 8 hours of acetaminophen ingestion, but giving it later is also useful. […] Patients with hepatitis B-induced acute liver failure should be treated with entecavir or tenofovir. Although this treatment may not change the course of acute liver failure or accelerate the recovery, it can prevent reinfection in the transplanted liver if liver transplant becomes indicated. […] Guidelines advise starting prednisone 40 to 60 mg/day and placing the patient on the liver transplant list. […] Once Wilson disease is suspected, the patient should be listed for liver transplant because death is almost certain without it. […] Although initially used only in patients with acetaminophen-induced liver failure, acetylcysteine has also shown benefit in patients with acute liver failure from other causes.

• #43 Management of acute liver failure. Clinical guideline from the Catalan Society of Digestology | Gastroenterología y Hepatología (English Edition)

  https://www.elsevier.es/en-revista-gastroenterologia-hepatologia-english-edition–382-articulo-management-acute-liver-failure-clinical-S2444382419300124

  Immunosuppressive treatment (corticosteroids) can be effective in cases of autoimmune origin if they are administered very early. […] ELT will always be required in ALF due to Wilson’s disease. […] The treatment of hyperthermia could limit the progression of ALF caused by this mechanism (heat stroke or ecstasy intake, often associated with hyperthermia). […] Patients with ALF requiring an ELT should be put on a priority transplant list (grade of evidence III, grade of recommendation 1). […] The artificial and bioartificial liver support systems should be used in the context of controlled clinical trials (grade of evidence II-1, grade of recommendation 1).

• #44 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  Barbiturate agents (thiopental or pentobarbital) may also be considered when severe ICH does not respond to other measures; administration of these drugs has been shown to effectively decrease ICP. […] Moderate hypothermia (32-34C) may prevent or control ICH in patients with acute liver failure. […] Hemodynamic derangements consistent with multiple organ failure occur in acute liver failure. […] In the absence of bleeding, it is usually not necessary to correct clotting abnormalities with fresh frozen plasma (FFP). […] Prothrombin time (PT) and partial thromboplastin time (PTT) become prolonged when plasma coagulation components are diluted to less than 30%, and abnormal bleeding occurs when they are less than 17%. […] Treat acetaminophen (paracetamol, APAP) overdose with N-acetylcysteine (NAC).

• #45 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Electrolyte deficiencies may require supplementation with sodium, potassium, phosphate, or magnesium. […] Hypoglycemia is treated with continuous glucose infusion (eg, 10% dextrose), and blood glucose should be monitored frequently because encephalopathy can mask the symptoms of hypoglycemia. […] Coagulopathy is treated with fresh frozen plasma if bleeding occurs or if an invasive procedure is planned. Fresh frozen plasma is otherwise avoided because it may result in volume overload and worsening of cerebral edema. Also, when fresh frozen plasma is used, clinicians cannot follow changes in international normalized ratio (INR), which are important because INR is an index of severity of acute liver failure and is thus sometimes a criterion for transplantation. Recombinant factor VII is sometimes used instead of or with fresh frozen plasma in patients with volume overload. Its role is evolving. H2 blockers may help prevent gastrointestinal bleeding.

• #46 GGC Medicines – Management of Acute Liver Failure

  https://handbook.ggcmedicines.org.uk/guidelines/gastrointestinal-system/management-of-acute-liver-failure/

  Discuss with Haematologist. […] The patient will require renal support if: K+ 6mmol/L, HCO3- 15mmol/L or Creatinine 400micromol/L. […] Rather than waiting until the strict criteria for transplantation are met, patients with severe acute liver failure should be discussed with the SLTU at an early stage. This should occur if: Prothrombin time 20 seconds or INR 2, pH 7.3 or H+ 50nmol/L, Hypoglycaemia, Conscious level impaired, Creatinine 200micromol/L, Any patient with encephalopathy, coagulopathy or renal impairment complicating acute liver injury should be discussed with SLTU.

• #47 Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure (Part I) | SCCM

  https://www.sccm.org/clinical-resources/guidelines/guidelines/guidelines-for-the-management-of-adult-acute-and-a

  We suggest using viscoelastic testing (thromboelastography/rotational thromboelastometry [ROTEM]) over measuring international normalized ratio (INR), platelet, and fibrinogen in critically ill patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Low […] We suggest using a transfusion threshold of 7 mg/dL, over other thresholds, for critically ill patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Low […] We suggest using low molecular weight heparin (LMWH) or vitamin K antagonists, over no anticoagulation, in patients with portal venous thrombosis or pulmonary embolus. Quality of Evidence: Very Low […] We suggest using low molecular weight heparin over pneumatic compression stockings for venous thromboembolism prophylaxis in hospitalized patients with acute on chronic liver failure. Quality of Evidence: Low

• #48 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Electrolyte deficiencies may require supplementation with sodium, potassium, phosphate, or magnesium. […] Hypoglycemia is treated with continuous glucose infusion (eg, 10% dextrose), and blood glucose should be monitored frequently because encephalopathy can mask the symptoms of hypoglycemia. […] Coagulopathy is treated with fresh frozen plasma if bleeding occurs or if an invasive procedure is planned. Fresh frozen plasma is otherwise avoided because it may result in volume overload and worsening of cerebral edema. Also, when fresh frozen plasma is used, clinicians cannot follow changes in international normalized ratio (INR), which are important because INR is an index of severity of acute liver failure and is thus sometimes a criterion for transplantation. Recombinant factor VII is sometimes used instead of or with fresh frozen plasma in patients with volume overload. Its role is evolving. H2 blockers may help prevent gastrointestinal bleeding.

• #49 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  When enteral feeding via a feeding tube is not feasible (eg, as in a patient with paralytic ileus), institute total parenteral nutrition (TPN). […] Potential complications of acute liver failure include seizures, hemorrhage, infection, renal failure, and metabolic imbalances. […] The first step in management is to correct coagulopathy. […] Acute renal failure is a frequent complication in patients with acute liver failure and may be due to dehydration, hepatorenal syndrome, or acute tubular necrosis. […] When dialysis is needed, continuous (ie, continuous venovenous hemodialysis [CVVHD]) rather than intermittent renal replacement therapy is preferred. […] Alkalosis and acidosis occur in acute liver failure. Identify and treat the underlying cause.

• #50 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  When enteral feeding via a feeding tube is not feasible (eg, as in a patient with paralytic ileus), institute total parenteral nutrition (TPN). […] Potential complications of acute liver failure include seizures, hemorrhage, infection, renal failure, and metabolic imbalances. […] The first step in management is to correct coagulopathy. […] Acute renal failure is a frequent complication in patients with acute liver failure and may be due to dehydration, hepatorenal syndrome, or acute tubular necrosis. […] When dialysis is needed, continuous (ie, continuous venovenous hemodialysis [CVVHD]) rather than intermittent renal replacement therapy is preferred. […] Alkalosis and acidosis occur in acute liver failure. Identify and treat the underlying cause.

• #51 Acute Liver Failure (ALF) – EMCrit Project

  https://emcrit.org/ibcc/alf/

  Patients with acute hepatic failure can deteriorate rapidly. Especially if the patient is a potential transplant candidate, it is often safest to pursue early transfer to a liver transplant center. […] N-acetylcysteine should be given for both acetaminophen and non-acetaminophen liver failure. Acetaminophen toxicity is the #1 cause of liver failure in many developed nations. This may result from suicide attempts or medication errors (e.g., simultaneous use of several acetaminophen-containing cold medications). […] N-acetylcysteine improves transplant-free survival even in hepatic failure not due to acetaminophen toxicity. […] Consider empiric therapy for hepatorenal syndrome, including albumin and vasopressors. Early initiation of dialysis may assist in ammonia clearance, so this is recommended by the SCCM guidelines and European guidelines.

• #52 Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure (Part I) | SCCM

  https://www.sccm.org/clinical-resources/guidelines/guidelines/guidelines-for-the-management-of-adult-acute-and-a

  We recommend using vasopressors, over not using vasopressors, in critically ill patients with acute on chronic liver failure who develop hepatorenal syndrome (HRS). Quality of Evidence: Moderate […] We recommend targeting a serum blood glucose of 110-180 mg/dL in patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Moderate […] We suggest using stress-dose glucocorticoids in the treatment of septic shock in patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Low […] We suggest against using a low protein goal in patients with acute liver failure or acute on chronic liver failure, but rather targeting protein goals comparable with critically ill patients without liver failure (1.2 2.0g protein/kg dry or ideal body weight per day [IBW/d]). Quality of Evidence: Very Low

• #53 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  The most important aspect of treatment in patients with acute liver failure is to provide good intensive care support. […] Patients with grade II encephalopathy should be transferred to the intensive care unit (ICU) for monitoring. As encephalopathy progresses, protection of the airway becomes increasingly important. […] Most patients with acute liver failure tend to develop some degree of circulatory dysfunction. Careful attention should be paid to fluid management and hemodynamics. […] Monitoring of metabolic parameters, surveillance for infection, maintenance of nutrition, and prompt recognition of gastrointestinal bleeding are crucial. […] Coagulation parameters, complete blood cell count, and metabolic panel should be checked frequently. Serum aminotransferases and bilirubin are generally measured daily to follow the course of the disease.

• #54 Management of acute liver failure | Deranged Physiology

  https://derangedphysiology.com/main/required-reading/gastrointestinal-intensive-care/Chapter-113/management-acute-liver-failure

  There are only a handful of conditions which have reliable treatment options beyond normal ICU support. […] Beyond this, all treatment is „supportive”, i.e. there is nothing to be done for the primary cause of liver failure. One can merely stand by and correct all the various abnormalities which take place in the organism. The real definitive solution is transplantation, The EASL guidelines (2017) claim a survival of ~ 80% from this procedure. […] Management plans should include the following points: Intubate the patient for airway protection, as they will be obtunded (and to control the CO2). The patient with fulminant liver failure is very likely to require intubation at some stage. […] Haemodiafiltration- continuously – to remove ammonia. This prevents acute cerebral oedema. […] Anticipate coagulopathy. Administer Vitamin K empirically, however little that is expected to have. […] Vigilant surveillance for sepsis: they are prone to it, and it makes the encephalopathy worse. The EASL guidelines (2017) recommend daily surveillance cultures.

• #55 Acute liver failure – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/acute-liver-failure/diagnosis-treatment/drc-20352868

  A healthcare professional also will typically work to control symptoms and try to prevent complications caused by acute liver failure. Care may include: […] Relieving pressure caused by excess fluid in the brain. Cerebral edema caused by acute liver failure can increase pressure on the brain. Medicines can help reduce the fluid buildup in your brain. […] Screening for infections. Your medical team may take samples of your blood and urine every now and then to be tested for infection. If your team suspects that you have an infection, you’ll receive medicines to treat the infection. […] Preventing severe bleeding. Your care team can give you medicines to reduce the risk of bleeding. If you lose a lot of blood, tests may be done to find the source of the blood loss. Blood transfusions may be needed.

• #56 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  To reduce cerebral edema: Renal replacement therapy in acute liver failure helps clear ammonia and predicts reduced mortality if initiated early. The European Association for the Study of the Liver (EASL) guidelines on acute liver failure recommend consideration of renal replacement therapy in patients with liver failure and markedly elevated ammonia and/or progressive encephalopathy. […] Seizures are treated with phenytoin; benzodiazepines are avoided or used only in low doses because they cause sedation. […] Infection is treated with antibacterial and/or antifungal drugs; treatment is started as soon as patients show any sign of infection (eg, fever; localizing signs; deterioration of hemodynamics, mental status, or renal function). Because signs of infection overlap with those of acute liver failure, infection is likely to be overtreated pending culture results.

• #57 Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure (Part I) | SCCM

  https://www.sccm.org/clinical-resources/guidelines/guidelines/guidelines-for-the-management-of-adult-acute-and-a

  We suggest using viscoelastic testing (thromboelastography/rotational thromboelastometry [ROTEM]) over measuring international normalized ratio (INR), platelet, and fibrinogen in critically ill patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Low […] We suggest using a transfusion threshold of 7 mg/dL, over other thresholds, for critically ill patients with acute liver failure or acute on chronic liver failure. Quality of Evidence: Low […] We suggest using low molecular weight heparin (LMWH) or vitamin K antagonists, over no anticoagulation, in patients with portal venous thrombosis or pulmonary embolus. Quality of Evidence: Very Low […] We suggest using low molecular weight heparin over pneumatic compression stockings for venous thromboembolism prophylaxis in hospitalized patients with acute on chronic liver failure. Quality of Evidence: Low

• #58 Acute liver failure – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/acute-liver-failure/diagnosis-treatment/drc-20352868

  People with acute liver failure often receive treatment in the intensive care unit of a hospital in a facility that can perform a liver transplant, if necessary. A healthcare professional may try to treat the liver damage itself, but in many cases, treatment involves controlling complications and giving the liver time to heal. […] Acute liver failure treatments may include: […] Medicines to reverse poisoning. Acute liver failure caused by acetaminophen overdose is treated with a medicine called acetylcysteine. This medicine also may help treat other causes of acute liver failure. Mushroom and other poisonings also may be treated with medicines that can reverse the effects of the toxin and may reduce liver damage. […] Liver transplant. When acute liver failure can’t be reversed, the only treatment may be a liver transplant. During a liver transplant, a surgeon removes the damaged liver and replaces it with a healthy liver from a donor.

• #59 Acute Liver Failure | Conditions and Treatments | Center for Liver Disease & Transplantation | Columbia University Department of Surgery

  https://columbiasurgery.org/conditions-and-treatments/acute-liver-failure

  Medications can treat acute liver failure caused by overdoses and toxins. In many other cases, a liver transplantation is required. […] Depending on its cause, there are two treatments for acute liver failure: medication and transplantation. Because acute liver failure can develop so quickly and is fatal, it is vital to seek treatment immediately. […] When acute liver failure is caused by ingesting toxic substances, acetaminophen overdose, or viral hepatitis, it can often be treated through medication. […] For many other cases of acute liver failure, a liver transplantation is the only treatment option. This involves removing the diseased liver and replacing it with a healthy donor liver. […] Because of how quickly acute liver failure can progress, patients who are eligible for a liver transplantation will be given a status one classification on the transplant waiting list. This lets them bypass other patients and receive a donor liver much sooner, often within just 48 to 72 hours.

• #60 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Nutritional support may be necessary if patients cannot eat. Severe protein restriction is unnecessary; 60 g/day is recommended. […] Acute acetaminophen toxicity is treated with N-acetylcysteine. Because chronic acetaminophen toxicity can be difficult to diagnose, use of N-acetylcysteine should be considered if no cause for acute liver failure is evident. Whether N-acetylcysteine has a slight beneficial effect on patients with acute liver failure due to other conditions is under study. […] Liver transplantation results in average 1-year survival rates of about 84%. Transplantation is thus recommended if prognosis without transplantation is worse. However, prediction is difficult and scores, such as King’s College criteria and the APACHE II (Acute Physiologic Assessment and Chronic Health Evaluation II) score, are not sufficiently sensitive and specific to be used as the only criteria for transplantation; thus, they are used as adjuncts to clinical judgment (eg, based on risk factors).

• #61 Acute Liver Failure – Hepatic and Biliary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/acute-liver-failure

  Nutritional support may be necessary if patients cannot eat. Severe protein restriction is unnecessary; 60 g/day is recommended. […] Acute acetaminophen toxicity is treated with N-acetylcysteine. Because chronic acetaminophen toxicity can be difficult to diagnose, use of N-acetylcysteine should be considered if no cause for acute liver failure is evident. Whether N-acetylcysteine has a slight beneficial effect on patients with acute liver failure due to other conditions is under study. […] Liver transplantation results in average 1-year survival rates of about 84%. Transplantation is thus recommended if prognosis without transplantation is worse. However, prediction is difficult and scores, such as King’s College criteria and the APACHE II (Acute Physiologic Assessment and Chronic Health Evaluation II) score, are not sufficiently sensitive and specific to be used as the only criteria for transplantation; thus, they are used as adjuncts to clinical judgment (eg, based on risk factors).

• #62 Acute liver failure – Wikipedia

  https://en.wikipedia.org/wiki/Acute_liver_failure

  Liver transplant […] Treatment includes liver transplant. […] Because ALF often involves the rapid deterioration of mental status and the potential for multiorgan failure, patients should be managed in the intensive care unit. […] For patients not at a transplant center, the possibility of rapid progression of ALF makes early consultation with a transplant facility critical. […] Accordingly, plans for transfer to a transplant center should begin in patients with any abnormal mentation. […] Early institution of antidotes or specific therapy may prevent the need for liver transplantation and reduce the likelihood of poor outcome. […] Patients with grade III encephalopathy should be transferred to a liver transplant facility and listed for transplantation. […] The advent of transplantation has changed survival from as low as 15% in the pretransplant era to more than 60% today.

• #63 Acute Liver Failure | Conditions and Treatments | Center for Liver Disease & Transplantation | Columbia University Department of Surgery

  https://columbiasurgery.org/conditions-and-treatments/acute-liver-failure

  Medications can treat acute liver failure caused by overdoses and toxins. In many other cases, a liver transplantation is required. […] Depending on its cause, there are two treatments for acute liver failure: medication and transplantation. Because acute liver failure can develop so quickly and is fatal, it is vital to seek treatment immediately. […] When acute liver failure is caused by ingesting toxic substances, acetaminophen overdose, or viral hepatitis, it can often be treated through medication. […] For many other cases of acute liver failure, a liver transplantation is the only treatment option. This involves removing the diseased liver and replacing it with a healthy donor liver. […] Because of how quickly acute liver failure can progress, patients who are eligible for a liver transplantation will be given a status one classification on the transplant waiting list. This lets them bypass other patients and receive a donor liver much sooner, often within just 48 to 72 hours.

• #64 Defining and Managing Acute Liver Failure | AASLD

  https://www.aasld.org/liver-fellow-network/core-series/back-basics/defining-and-managing-acute-liver-failure

  Acute liver failure (ALF) is defined by the following criteria: […] Survival has increased significantly from 20% to greater than 60% in the past few decades due to improvements in supportive critical care and use of liver transplantation in selected patients timely recognition of ALF is crucial! […] Recognize the role of liver transplantation in managing acute liver failure. […] Empiric N-acetylcysteine (NAC) infusion is often started while awaiting workup for ALF. It is also the treatment of choice for acetaminophen toxicity. NAC also improves outcomes in non-acetaminophen ALF as some reports suggest it improves transplant-free survival if used in early-stages of ALF. […] Although improvements in medical care have significantly lowered mortality rates, LT is being implemented in approximately 30% of patients with ALF, and offers a life-saving treatment. […] Early referral to a LT center should be pursued as soon as ALF is clinically suspected in order to expedite transplant evaluation for patients who need it.

• #65 Acute Liver Failure: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/177354-overview

  Liver transplantation is the definitive treatment for acute liver failure. In selected patients for whom no allograft is immediately available, consider support with a bioartificial liver. This is a short-term measure that only leads to survival if the liver spontaneously recovers or is replaced. […] Nonbiologic extracorporeal liver support systems, such as hemodialysis, hemofiltration, charcoal hemoperfusion, plasmapheresis, and exchange transfusions permit temporary liver support until a suitable donor liver is found. However, no controlled study has shown long-term benefit. […] See Treatment and Medication for more details.

• #66 Acute Liver Failure: Summary of a Workshop

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3381946/

  The role of hypothermia in clinical practice remains unclear. […] Plasmapheresis decreased plasma ammonia levels and improved hepatic encephalopathy, generally within hours. […] Hepatic assist devices generally fall into two categories: (1) non cell-based detoxification systems and (2) cell-based systems to provide metabolic support as well as detoxification (bioartificial liver). […] Bioartificial liver devices are meant to allow time for spontaneous recovery or for the retrieval of a liver graft (bridge to transplantation) and to manage the systemic manifestations of ALF. […] The next generation of bioartificial liver systems employ a hybrid or multimodal approach, combining albumin dialysis, charcoal therapy, adsorbent therapy, and dialysis with hepatocyte cell-based therapy.

• #67 Acute Liver Failure Treatment & Management: Approach Considerations, Airway Protection, Management of Encephalopathy and Cerebral Edema

  https://emedicine.medscape.com/article/177354-treatment

  The protective effect of NAC is greatest when administered within 8 hours of ingestion; however, when indicated, administer NAC regardless of the time since the overdose. […] Liver transplantation is the definitive treatment in liver failure, but a detailed discussion is beyond the scope of this article. […] In selected patients for whom no allograft is immediately available, consider support with a bioartificial liver. […] These modalities permit temporary liver support until a suitable donor liver is found. […] Among the liver support systems currently available, albumin dialysis using the molecular adsorbent recirculating system (MARS) is the one that has been most extensively investigated. […] Patients with acute liver failure are, by necessity, on nothing by mouth (NPO) status.

• #68 Liver Failure – End Stage Liver Disease – UChicago Medicine

  https://www.uchicagomedicine.org/conditions-services/liver-diseases-hepatology/liver-failure

  Your treatment will depend on the cause of your liver failure. However, in many cases, the best treatment for advanced liver disease is a liver transplant. […] In many cases, the only treatment for a failing liver is a liver transplant. But sometimes, an acute or hereditary cause can be treated to reverse the condition. […] The Molecular Adsorbent Recirculating System (MARS) is a liver dialysis machine used to perform some of the function of the liver. It removes protein-bound and water-soluble toxins from the blood and reduces the amounts of toxins that reach the brain. […] Waiting for a donor liver is not the only option available to liver failure patients. Living liver donors can give part of their healthy liver to a transplant patient and end their long wait for treatment. […] Acute liver failure is a medical emergency, and UChicago Medicine has state-of-the-art intensive care units for monitoring patients with this condition. Treatment will depend on the cause of your underlying liver failure. Medications may help treat viral hepatitis, autoimmune hepatitis, acetaminophen overdoses, poisonings and other causes. If treatment is not effective, our liver specialists will evaluate you for a possible liver transplant.

• #69 Acute Liver Failure: Summary of a Workshop

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3381946/

  The role of hypothermia in clinical practice remains unclear. […] Plasmapheresis decreased plasma ammonia levels and improved hepatic encephalopathy, generally within hours. […] Hepatic assist devices generally fall into two categories: (1) non cell-based detoxification systems and (2) cell-based systems to provide metabolic support as well as detoxification (bioartificial liver). […] Bioartificial liver devices are meant to allow time for spontaneous recovery or for the retrieval of a liver graft (bridge to transplantation) and to manage the systemic manifestations of ALF. […] The next generation of bioartificial liver systems employ a hybrid or multimodal approach, combining albumin dialysis, charcoal therapy, adsorbent therapy, and dialysis with hepatocyte cell-based therapy.

• #70

  https://journals.lww.com/co-criticalcare/fulltext/2007/04000/acute_liver_failure__liver_support_therapies.17.aspx

  We summarize the therapeutic approach to patients with acute liver failure with the main focus on bioartificial and artificial liver support. […] Bioartificial liver support systems use hepatocytes in an extracorporeal device connected to the patient’s circulation. Artificial liver support is intended to remove protein-bound toxins and water-soluble toxins without providing synthetic function. […] Mortality in patients with acute liver failure is still unacceptably high. The most effective treatment, liver transplantation, is a limited resource and so other therapeutic options to bridge patients to recovery or stabilization have to be considered. Better understanding of the pathophysiology of acute liver failure and device development is necessary to achieve the elusive goal of effective extracorporeal liver assist.

• #71 Acute Liver Failure: Summary of a Workshop

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3381946/

  The role of hypothermia in clinical practice remains unclear. […] Plasmapheresis decreased plasma ammonia levels and improved hepatic encephalopathy, generally within hours. […] Hepatic assist devices generally fall into two categories: (1) non cell-based detoxification systems and (2) cell-based systems to provide metabolic support as well as detoxification (bioartificial liver). […] Bioartificial liver devices are meant to allow time for spontaneous recovery or for the retrieval of a liver graft (bridge to transplantation) and to manage the systemic manifestations of ALF. […] The next generation of bioartificial liver systems employ a hybrid or multimodal approach, combining albumin dialysis, charcoal therapy, adsorbent therapy, and dialysis with hepatocyte cell-based therapy.

• #72 Management of acute liver failure. Clinical guideline from the Catalan Society of Digestology | Gastroenterología y Hepatología (English Edition)

  https://www.elsevier.es/en-revista-gastroenterologia-hepatologia-english-edition–382-articulo-management-acute-liver-failure-clinical-S2444382419300124

  Immunosuppressive treatment (corticosteroids) can be effective in cases of autoimmune origin if they are administered very early. […] ELT will always be required in ALF due to Wilson’s disease. […] The treatment of hyperthermia could limit the progression of ALF caused by this mechanism (heat stroke or ecstasy intake, often associated with hyperthermia). […] Patients with ALF requiring an ELT should be put on a priority transplant list (grade of evidence III, grade of recommendation 1). […] The artificial and bioartificial liver support systems should be used in the context of controlled clinical trials (grade of evidence II-1, grade of recommendation 1).

• #73 Acute-On-Chronic Liver Failure: Current Interventional Treatment Options and Future Challenges

  https://www.mdpi.com/2075-4426/13/7/1052

  Extracorporeal liver support systems (ECLS) such as albumin dialysis have been and are currently being evaluated, and new approaches and experimental therapeutic strategies are being tested. […] The only curative and potentially life-saving therapeutic option for patients with AD and ACLF remains LT. […] Recent data have generated a consensus that patients with ACLF, especially grades 1 and 2, should be listed for LT and benefit from timely evaluation for LT. […] Overall, these findings advocate for the need to discuss the necessity of improving and modifying the current allocation systems to better reflect waitlist mortality, and especially to adequately reflect the prognosis of ACLF patients.

• #74 Acute liver failure – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/acute-liver-failure/diagnosis-treatment/drc-20352868

  Providing nutritional support. If you’re not able to eat, you may need supplements to treat nutritional deficiencies. […] Scientists continue to research new treatments for acute liver failure, especially those that could reduce or delay the need for a liver transplant. While several possible future treatments are being explored, it’s important to remember that the treatments are experimental and may not yet be available. […] These treatments are among those being studied: […] Artificial hepatic assist devices. A machine would do the job of the liver, much like dialysis helps when the kidneys stop working. […] Hepatocyte transplantation. Transplanting only the cells of the liver not the entire organ may temporarily delay the need for a liver transplant. […] Auxiliary liver transplantation. This procedure involves removing a small piece of your liver and replacing it with a similarly sized graft. […] Xenotransplantation. This type of transplant replaces the human liver with a liver from an animal or other nonhuman source.

• #75 Acute liver failure – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/acute-liver-failure/diagnosis-treatment/drc-20352868

  Providing nutritional support. If you’re not able to eat, you may need supplements to treat nutritional deficiencies. […] Scientists continue to research new treatments for acute liver failure, especially those that could reduce or delay the need for a liver transplant. While several possible future treatments are being explored, it’s important to remember that the treatments are experimental and may not yet be available. […] These treatments are among those being studied: […] Artificial hepatic assist devices. A machine would do the job of the liver, much like dialysis helps when the kidneys stop working. […] Hepatocyte transplantation. Transplanting only the cells of the liver not the entire organ may temporarily delay the need for a liver transplant. […] Auxiliary liver transplantation. This procedure involves removing a small piece of your liver and replacing it with a similarly sized graft. […] Xenotransplantation. This type of transplant replaces the human liver with a liver from an animal or other nonhuman source.

• #76 Acute liver failure | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/acute-liver-failure?content_id=CON-20306104

  Transplanting only the cells of the liver not the entire organ may temporarily delay the need for a liver transplant. […] This procedure involves removing a small piece of your liver and replacing it with a similarly sized graft. […] This type of transplant replaces the human liver with a liver from an animal or other nonhuman source.

• #77 Mesenchymal Stem Cell Therapy in Acute Liver Failure

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl220417

  Acute liver failure (ALF) is a severe liver disease syndrome with rapid deterioration and high mortality. Liver transplantation is the most effective treatment, but the lack of donor livers and the high cost of transplantation limit its broad application. […] In recent years, there has been no breakthrough in the treatment of ALF, and the application of stem cells in the treatment of ALF is a crucial research field. Mesenchymal stem cells (MSCs) are widely used in disease treatment research due to their abundant sources, low immunogenicity, and no ethical restrictions. Although MSCs are effective for treating ALF, the application of MSCs to ALF needs to be further studied and optimized. […] The main treatments for ALF include conventional medical treatment, artificial liver support systems, and liver transplantation.

• #78 Mesenchymal Stem Cell Therapy in Acute Liver Failure

  https://www.gutnliver.org/journal/view.html?doi=10.5009/gnl220417

  Previous studies have shown that MSCs treat ALF by differentiating into hepatocyte-like cells (HLCs), regulating immune cells, and secreting therapeutic factors. […] The overactivation of the immune system plays an essential role in initiating and accelerating ALF. MSCs can regulate the functions of various immune cells, so many studies have shown that MSCs treat ALF mainly through immune regulation. […] Various substances derived from MSCs have therapeutic effects on ALF, including cytokines, conditioned medium (CM), and exosomes. […] The effectiveness of MSCs in the treatment of ALF has been confirmed, but how to improve its efficacy is worth further study. […] Indeed, MSCs combined with other therapies may have better outcomes for ALF than MSCs therapy alone. […] Many studies have proved that MSCs can effectively treat ALF in animal models. Similarly, MSCs have therapeutic effects on patients with liver failure in clinical trials. […] The course of MSCs therapy for liver failure is uncertain. […] MSCs treat ALF by differentiating into HLCs, regulating immune cells, and secreting therapeutic factors.

• #79 Acute liver failure – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/acute-liver-failure/diagnosis-treatment/drc-20352868

  Providing nutritional support. If you’re not able to eat, you may need supplements to treat nutritional deficiencies. […] Scientists continue to research new treatments for acute liver failure, especially those that could reduce or delay the need for a liver transplant. While several possible future treatments are being explored, it’s important to remember that the treatments are experimental and may not yet be available. […] These treatments are among those being studied: […] Artificial hepatic assist devices. A machine would do the job of the liver, much like dialysis helps when the kidneys stop working. […] Hepatocyte transplantation. Transplanting only the cells of the liver not the entire organ may temporarily delay the need for a liver transplant. […] Auxiliary liver transplantation. This procedure involves removing a small piece of your liver and replacing it with a similarly sized graft. […] Xenotransplantation. This type of transplant replaces the human liver with a liver from an animal or other nonhuman source.

• #80 Acute liver failure – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/acute-liver-failure/diagnosis-treatment/drc-20352868

  Providing nutritional support. If you’re not able to eat, you may need supplements to treat nutritional deficiencies. […] Scientists continue to research new treatments for acute liver failure, especially those that could reduce or delay the need for a liver transplant. While several possible future treatments are being explored, it’s important to remember that the treatments are experimental and may not yet be available. […] These treatments are among those being studied: […] Artificial hepatic assist devices. A machine would do the job of the liver, much like dialysis helps when the kidneys stop working. […] Hepatocyte transplantation. Transplanting only the cells of the liver not the entire organ may temporarily delay the need for a liver transplant. […] Auxiliary liver transplantation. This procedure involves removing a small piece of your liver and replacing it with a similarly sized graft. […] Xenotransplantation. This type of transplant replaces the human liver with a liver from an animal or other nonhuman source.

• #81 Defining and Managing Acute Liver Failure | AASLD

  https://www.aasld.org/liver-fellow-network/core-series/back-basics/defining-and-managing-acute-liver-failure

  Acute liver failure (ALF) is defined by the following criteria: […] Survival has increased significantly from 20% to greater than 60% in the past few decades due to improvements in supportive critical care and use of liver transplantation in selected patients timely recognition of ALF is crucial! […] Recognize the role of liver transplantation in managing acute liver failure. […] Empiric N-acetylcysteine (NAC) infusion is often started while awaiting workup for ALF. It is also the treatment of choice for acetaminophen toxicity. NAC also improves outcomes in non-acetaminophen ALF as some reports suggest it improves transplant-free survival if used in early-stages of ALF. […] Although improvements in medical care have significantly lowered mortality rates, LT is being implemented in approximately 30% of patients with ALF, and offers a life-saving treatment. […] Early referral to a LT center should be pursued as soon as ALF is clinically suspected in order to expedite transplant evaluation for patients who need it.

• #82 Management of acute liver failure | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/nrgastro.2009.127

  Acute liver failure (ALF) is a syndrome of diverse etiology, in which patients without previously recognized liver disease sustain a liver injury that results in rapid loss of hepatic function. […] Management decisions made by clinicians who initially assess individuals with ALF can drastically affect these patients’ outcomes. […] We highlight advances in the intensive care management of patients with ALF that have contributed to a marked improvement in their overall survival over the past 20 years. These advances include therapies that limit the extent of liver injury and maximize the likelihood of spontaneous recovery and approaches to enable prevention, recognition and early treatment of complications that lead to multi-organ-system failure, the most common cause of death. […] Administration of N-acetylcysteine to all patients with ALF regardless of its etiology may become standard-of-care.

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