Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version. Overview Acute liver failure is loss of liver function that occurs rapidly — in days or weeks — usually in a person who has no preexisting liver disease.
Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Feldman M, et al. Elsevier; Accessed Sept. If the ALF patient is not already hospitalized at a transplant program, it is important to consider early transfer to a liver transplant center, preferably one with experience managing patients with ALF. Doing so allows the patient to be evaluated by the transplant center staff to determine candidacy for liver transplant before the patient becomes too ill.
In recognition of their very poor short-term prognosis, patients with ALF enjoy a special designation on the waiting list called "status 1" that equates to the highest priority for transplant possible. As a result, patients listed for transplant with ALF essentially bypass thousands of patients with chronic liver disease who are waiting on the list, often for many months or even years. In many parts of the country, the waiting time for liver transplant for patients with status 1 listing is only 48 to 72 hours, compared with many months for those listed with chronic liver disease.
Because the chances of rapidly dying with severe ALF are high, and the waiting times for transplant are unpredictable, listing appropriate patients with ALF as soon as they meet these criteria is important. Otherwise, they may develop complications that preclude liver transplantation, such as severe and untreatable cerebral edema or multi-organ failure.
Obviously, patients must also meet other criteria for liver transplant candidacy see Liver Transplant Knol. It should be noted that, while UNOS listing is a necessary first step for liver transplant, listing is not a guarantee of liver transplant. For example, if the ALF patient develops major complications while awaiting liver transplant, such as unmanageable cerebral edema, or has contraindications to transplant e. The final decision about whether to proceed with liver transplant is often made at the time a donor organ becomes available and is one of the most difficult decisions that liver transplant physicians hepatologists and surgeons face.
Deciding to proceed with liver transplant, while potentially life saving, commits the patient not only to a major surgical procedure but also a lifetime of taking immunosuppressant and other medications. However, deciding not to proceed based on the hope that the patient's own liver will regenerate and recover, may result in a poor outcome if the patient unexpectedly takes a turn for the worse and another donor liver is not readily available. Survival following liver transplant for ALF has historically been lower than that for chronic liver disease.
Since there are multiple causes of acute liver failure that all lead to essentially the same syndrome, no single measure is likely to be effective in preventing all cases. However, several measures can be envisioned that, if successfully executed, should significantly decrease the incidence of ALF in the US. For example, vaccination for hepatitis A and B has probably contributed to the declining incidence of ALF from viral hepatitis.
Public health initiatives, including guidelines regarding appropriate food handling, have likely also contributed by reducing the incidence of food-borne hepatitis A. Certainly, other areas deserve attention as well, including public education about the potential dangers of eating wild mushrooms. ALF is potentially reversible. The ALF patient's outcome depends on the balance between liver injury on the one end and liver regeneration and repair on the other. If the liver injury can be attenuated, or the liver repair and regenerative responses can be enhanced, then recovery is likely.
Recent advances in molecular and cell biology have resulted in the identification of molecular targets that might soon be purposefully manipulated to tip the balance and achieve this goal.
The Acute Liver Failure Study Group consists of investigators and coordinators from 23 academic medical centers, all of which perform liver transplants, that receive support from the National Institute of Diabetes, Digestive, and Kidney Diseases to study the epidemiology, outcome and pathogenesis of ALF in the US. Since the inception of the group in , more than ALF patients have enrolled in the study, which includes a detailed clinical database as well as a serum and liver tissue bank.
The group also has conducted a controlled, randomized, double blind trial of the use of an anti-oxidant, N-acetyl cysteine NAC , for the treatment of ALF not due to acetaminophen. Information about mushrooms and mushroom poisoning.
Text on this page, and images not specifically attributed, were adapted from Davern, Tim. Acute Liver Failure [Internet]. Version Acute Liver Failure ALF Acute liver failure ALF also called fulminant hepatic failure is a rare condition characterized by the abrupt onset of severe liver injury, manifest as a profound liver dysfunction as well as a confusional state called hepatic encephalopathy in individuals with no prior history of liver disease. ALF vs. Acute-on-Chronic Liver Disease Patients who suffer an acute deterioration of previously stable cirrhosis from alcohol or chronic hepatitis may have a life-threatening illness, but they do not have ALF.
Incidence ALF is relatively rare. Causes As shown in the table, a diverse array of insults can cause ALF. Other Medications Scores of drugs other than acetaminophen can also produce severe liver injury see Drug Induced hepatitis Knol. Mushrooms Certain mushrooms, notably Amanita phalloides photo , also called the "death cap", contain very potent liver toxins. Other conditions Several other conditions that affect the liver can also cause ALF. Autoimmune Hepatitis Autoimmune hepatitis is a relatively rare condition in which the immune system of the affected individual attacks the liver in a process that is broadly analogous to liver transplant rejection, only without the transplant.
Complications of Pregnancy ALF may rarely occur in pregnancy, usually during the last trimester and most often in patients with preeclampsia pregnancy-associated hypertension and loss of protein in the urine. Back to Top Symptoms Most patients who develop ALF become ill very rapidly, and the interval from onset of illness to near total liver collapse may be as short as a week or less. Back to Top Diagnosis Obtaining a detailed and accurate medical history from patients with ALF can be very challenging, if not impossible, due to the presence of an altered mental status.
Back to Top Prognosis The liver performs a myriad of vital functions including: processing proteins, sugars, fats, and vitamins removal of toxic substances e. Back to Top Treatment ALF is a medical emergency and requires prompt medical evaluation and treatment. Common antidotes are summarized in the table below. Back to Top Cerebral Edema Brain swelling, also called cerebral edema, is defined as a pathological increase in total brain water leading to an increase in brain volume.
Treatments Most of the treatments used to control cerebral edema in ALF have been borrowed from the literature on treatment of brain swelling that accompanies head trauma. Back to Top Renal failure Renal kidney failure is common in patients with ALF and may be caused by a variety of factors.
Accordingly, coagulation abnormalities are typical of ALF. Intravascular coagulation and fibrinolysis leading to consumption of platelets and coagulation factors, also contributes to coagulopathy.
In addition, vitamin K deficiency has been seen in patients with ALF, which contributes to the decreased production of clotting factors. Thrombocytopenia is commonly seen in patients with ALF. Despite the presence of coagulopathy in ALF, clinically significant spontaneous bleeding is uncommon. Routine administration of fresh frozen plasma is discouraged in ALF not only because of lack of need, but also because it results in improvement in coagulation metrics eg, prothrombin time, INR , one of the most important metrics related to patient improvement.
Selective use prior to placement of intracranial pressure ICP measurement devices, other invasive procedures, or in response to clinically significant bleeding is advocated. Gastrointestinal or genitourinary bleeding are the usual sites for spontaneous bleeding in ALF.
However, there is an increased risk of bleeding with invasive procedures in patients with ALF. Patients with ALF are prone to develop multiple infections due to a decrease in immunity. The presence of a fungal infection is a poor prognostic sign in patients with ALF. The mechanism for decreased immunity in ALF is multifactorial.
There is impaired functioning of the polymorphonuclear leukocytes, decreasing their ability of phagocytosis and opsonization.
Both cell-mediated and humoral immunity have been noted to be suboptimal. In addition, patients with ALF usually have multiple central and peripheral lines and indwelling catheters, which increase the risk of nosocomial infections. Furthermore, these patients may be on medications such as glucocorticoids or proton-pump inhibitors which further increase risk of infections. Acute renal failure is an important and a frequent complication of ALF and is mainly a result of the hemodynamic alterations in ALF.
The mechanism for renal failure is multifactorial. Initially it can be prerenal in etiology due to hypovolemia, but prolonged ischemia of renal tubules can cause progression to acute tubular necrosis. Functional renal failure similar to the hepatorenal syndrome in patients with cirrhosis may be seen in patients with ALF.
Certain etiologies for ALF such as that of acetaminophen toxicity, amanita poisoning, or an idiosyncratic reaction to trimethoprim-sulfamethoxazole, also cause direct renal toxicity and hence renal failure is more frequently seen in these patients. Hypoglycemia is an important complication of ALF. It contributes to altered mental status, and thus the true extent of hepatic encephalopathy may be unclear in the presence of hypoglycemia.
There are 2 main mechanisms that contribute to hypoglycemia in ALF: impaired gluconeogenesis in the injured liver in ALF; and decreased uptake of insulin by the hepatocytes.
This increases the insulin level in the peripheral blood resulting in hypoglycemia. Electrolyte abnormalities such as hyponatremia, hypokalemia, hypophosphatemia, and acid-base imbalances such as respiratory acidosis are commonly seen in ALF.
Hyponatremia, when present, is usually due to hypervolemia. Central nervous system induced hyperventilation in ALF leads to respiratory alkalosis. This in turn causes the kidneys to absorb hydrogen ions in exchange for potassium, thus resulting in hypokalemia. These electrolyte abnormalities may rarely result in cardiac arrhythmias contributing to mortality. There is no proven therapy for ALF and hence understanding the progression of ALF, from loss of hepatocyte function to the development of multiorgan failure, helps in disease management.
Diagnosis of ALF may be delayed in certain situations such as in patients presenting with altered mental status with minimal jaundice and absence of other features of ALF. A high index of suspicion is necessary in these cases as early intervention is imperative to decrease morbidity and mortality. Broadly, the management of ALF should involve Identification of the etiology of ALF whenever possible and initiation of specific treatment Supportive and symptomatic management of ALF, with timely transfer to the critical care unit Early discussion with liver transplant specialists and safe transfer of patients to a liver transplant center when required.
Identification and Treatment of underlying etiology Acetaminophen-induced hepatotoxicity A history of ingestion of acetaminophen and elevated serum acetaminophen levels indicate acetaminophen hepatotoxicity. Acetaminophen levels in the blood vary with the time from consumption, and thus a low acetaminophen level does not exclude acetaminophen-induced hepatotoxicity. Additionally, as the time of ingestion may be remote or unknown or occurring over several days, measuring acetaminophen levels in patients with liver tests suggesting liver failure may not yield meaningful information.
However it is still recommended to check levels in all patients with ALF. Hepatotoxicity is not typically seen soon after acetaminophen ingestion and the treatment of patients with acetaminophen toxicity differs from the treatment of patients with ALF. The Rumack-Mathew nomogram helps predict the development of hepatotoxicity in patients with acetaminophen toxicity. It should be given as soon as the diagnosis of acetaminophen toxicity is suspected.
In confirmed cases of acetaminophen toxicity, acetaminophen levels should be plotted on the nomogram to determine the risk of development of hepatotoxicity. If the risk is high, then NAC should be promptly started. NAC is most efficacious when given within 8 hours of ingestion. NAC has very few side effects and they are usually benign predominately nausea and vomiting; rash, urticarial, and bronchospasm rarely occur. Hence NAC should be administered in all patients with suspected or confirmed acetaminophen toxicity even if they present beyond 8 hours of presentation.
Hence it is recommended to give activated charcoal prior to NAC if acetaminophen ingestion is within 4 hours of presentation. However, intravenous NAC is more commonly used in clinical settings as a majority of patients with acetaminophen-induced hepatotoxicity have significant nausea, vomiting or altered mental status which makes use of oral NAC impractical. In patients with acetaminophen toxicity who have ALF, in addition to NAC, the general principles of supportive and symptomatic treatment of ALF in a critical care setting remains the mainstay of treatment.
These are described later in the chapter. Drug-induced hepatotoxicity is a diagnosis of exclusion. As noted earlier, a detailed medication history must be obtained. Any drug identified as the likely etiology of ALF has to be stopped immediately. In addition, all medications except for those that are absolutely essential should be discontinued. One prospective double-blind controlled trial showed that intravenous NAC improved transplant-free survival in patients with early stage nonacetaminophen-related ALF.
However in this study, patients with advanced coma grades did not show a benefit from NAC and required emergency liver transplantation. The diagnosis of mushroom poisoning induced ALF is made clinically and there is no available blood test to confirm the diagnosis. Activated charcoal and gastric lavage via nasogastric tube may be useful during initial hours after ingestion of mushroom. Supportive care and medical treatment should be instituted promptly in an attempt to decrease the need for liver transplantation.
Three drugs have been proposed to be efficacious and have been used in mushroom poisoning: penicillin G, silibinin silymarin or milk thistle , and NAC. Silibinin is not routinely available in the U. NAC at the same dosage as for acetaminophen-induced hepatotoxicity may be administered in mushroom poisoning.
However despite the presence of medical therapy, mushroom poisoning induced ALF has a high mortality rate without liver transplantation so these patients should be listed for transplantation at the earliest. All patients presenting with ALF should have acute hepatitis serology testing performed, even if another etiological agent has been identified.
If patients with acute hepatitis B-induced ALF undergo liver transplant, treatment with antiviral agent should be continued post-transplant to prevent recurrence. Patients, who are carriers of hepatitis B or have chronic hepatitis B infection and are to receive immunosuppression or chemotherapy, should receive prophylaxis with antiviral agents. Treatment of hepatic encephalopathy depends on the grade of hepatic encephalopathy.
Grade 1 hepatic encephalopathy can be managed in the medical floor with skilled nursing; however, beyond grade 1, all patients should be managed in an intensive care unit. As patients progress to grade 3 and 4 hepatic encephalopathy, intubation and mechanical ventilation, with elevation of the head of the bed, are necessary. The general steps involved in the management of hepatic encephalopathy include providing a peaceful environment to avoid agitation performing frequent neurological checks avoiding sedatives or using only short-acting benzodiazepines to control severe agitation consideration for liver transplantation and transfer to a transplant facility.
The goals in the treatment of hepatic encephalopathy are to prevent the onset of encephalopathy if possible, decrease the progression to severe grades of encephalopathy, and to minimize the development of cerebral edema and ICH, which can lead to cerebral herniation and death.
A computed tomography scan of the head is performed in most cases to rule out other causes of agitation or neurological decline. Role of lactulose. As discussed earlier, serum hyperammonemia plays an important role in the pathogenesis of hepatic encephalopathy and cerebral edema. Lactulose, when administered orally, decreases the enteral absorption of ammonia and has been used to treat and prevent hepatic encephalopathy in patients with cirrhosis. In patients with ALF, lactulose has not been shown to improve mortality.
Though it may be useful in decreasing blood ammonia levels and may have a beneficial effect on cerebral edema, one should watch for the development of gaseous distention of the bowel during its use and modify the dosage accordingly.
Similarly, use of antibiotics such as neomycin and rifaximin, have no clear benefit to treat hepatic encephalopathy in ALF and are not routinely recommended. The development of cerebral edema and ICH depends on the severity of hepatic encephalopathy. Intracranial hypertension needs aggressive management. Achieving hemodynamic stability. Maintaining cerebral perfusion is a key component in the treatment of hepatic encephalopathy as it lowers the development of ICH.
Fluid resuscitation, intravascular volume repletion, and occasionally vasopressors may be needed to maintain MAP, which in turn helps to maintain cerebral perfusion. However, large volume infusions of hypotonic fluids should however be avoided as they result in hyponatremia and cerebral edema.
Prognostic criteria are based primarily either on clinical and laboratory coagulation tests, serum bilirubin parameters, or on other parameters like liver volume. Prognostic criteria have been developed both from the East and the West; these are essentially similar except that the Western criteria take into account etiology drug overdose being the main cause of ALF there as well as jaundice-encephalopathy interval as factors for prognostication.
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