Acute liver failure

Acute liver failure (ALF) is defined as hepatic encephalopathy complicating acute liver injury. The most common etiologies are acute viral hepatitis A and B, medication overdose (e.g., acetaminophen), idiosyncratic drug reactions, ingestion of other toxins (e.g., amanita mushroom poisoning), and metabolic disorders (e.g., Reye's syndrome). Despite advances in intensive care management, mortality continues to be high (40-80%) and is partly related to ALF's complications, such as cerebral edema, sepsis, hypoglycemia, gastrointestinal bleeding, and acute renal failure. Several prognostic models have been developed to determine which patients will spontaneously recover. Treatment is directed at early recognition of the complications and general supportive measures. The only proven therapy for those who are unlikely to recover is liver transplantation. Therefore, recognition of ALF is paramount, and urgent referral to a transplant center is critical to assess transplantation status.     

Acute liver failure

Untreated acute liver failure (ALF) has a poor outcome and so rapid diagnosis and management is vital if the patient is to survive. ALF has such profound and widespread physiological consequences that whenever possible, patients with ALF should be managed in an intensive care unit. Management is to support the physiology and treat the underlying cause. Advice should be sought from a centre capable of performing liver transplantation. Should recovery seem unlikely, liver transplantation is a viable treatment option in some cases.     

Acute liver failure

Acute liver failure is characterized by a dynamic clinical course associated with high mortality. The main prognostic determinant is the development of extrahepatic complications. Close monitoring is mandatory, and prophylactic measures to avoid complications should be initiated. In case of complications, early and aggressive treatment is indicated. To date, artificial liver support devices are still in the experimental phase. Liver transplantation should be considered in patients with predictors of a poor spontaneous prognosis. Therefore, a transplant center should be contacted in every case of acute liver failure.     

Acute liver failure

Acute liver failure, also called fulminant hepatic failure, is characterized by sudden hepatic synthetic dysfunction associated with coagulopathy and hepatic encephalopathy. Acute liver failure has most recently been defined based on the timing from onset of jaundice to encephalopathy as follows: 1) hyperacute (1-7 days); 2) acute (8-28 days), and 3) subacute (29-60 days). Rapid onset of encephalopathy in hyperacute liver failure is paradoxically associated with highest rate of spontaneous recovery, and subacute liver failure is associated with worst prognosis. The etiology of liver failure is established by history, serologic assays, and exclusion of alternative causes. Acute liver failure is most frequently caused by drug hepatotoxicity, including acetaminophen toxicity and idiosyncratic drug reactions, with viral hepatitis playing a lesser role in recent surveys. A substantial number of cases have an indeterminate etiology. Major complications of acute liver failure that require active intervention include metabolic disorders, coagulopathy, cerebral edema, renal failure, and infection. The focus of management of acute liver failure is comprehensive supportive care in an intensive care unit and assessment of the need for liver transplantation.     

Acute liver failure

Opinion statement Acute liver failure (ALF) is an uncommon medical emergency whose rapid progression and high mortality demand early diagnosis and expert management, including immediate transfer of any potential case to facilities for intensive care and orthotopic liver transplantation (OLT). All patients with ALF must be screened aggressively for acetaminophen toxicity (history, serum levels, “hyperacute” presentation with renal failure), for other drugs, and viral hepatitis; rare causes of ALF should also be considered. After an acetaminophen overdose, N-acetylcysteine must be given as early as possible, preferably in the emergency room, but any patient with ALF should promptly receive N-acetylcysteine if there is suspicion of acetaminophen toxicity irrespective of the time of ingestion. Supportive care for all patients with ALF includes adequate enteral nutrition, aggressive screening and treatment of infection, prophylactic broad-spectrum antibiotics, and antifungal agents. Sedation with propofol is given for severe agitation or mechanical ventilation. With advanced coma grades, intensive care is needed with hemodynamic monitoring, ventilatory support, continuous renal replacement for renal failure, and intracranial pressure monitoring. Intracranial hypertension is treated with mannitol and/or acute short-term hyperventilation, but if the patient is refractory to treatment, mild-moderate hypothermia is achieved by a cooling blanket that is continued throughout OLT. Barbiturate coma is only used in refractory cases as the last treatment modality. Seizures are aggressively treated with phenytoin, with additional diazepam as needed. Candidacy and activation for OLT should be completed as early as possible in the course of ALF, especially in “hyperacute” cases such as acetaminophen toxicity. The final decision to proceed with OLT is made when a donor organ becomes available. King’s College Hospital criteria for OLT are still the best prognostic assessment for fatal outcome in ALF, but the criteria fail to identify some patients who will die.     

Acute liver failure in children

Acute liver failure (ALF) is a rare but devastating illness. Specific therapy to promote liver recovery is often not available, and the underlying cause of the liver failure is often unknown. This article examines current knowledge of the epidemiology, pathobiology, and treatment of ALF in children and identifies potential gaps in this knowledge for future study.     

急性肝衰竭最新认识

在美国生物化学、影像学和生物工程学研究所（NIBIB）及国立卫生研究院（NIH）罕见疾病部门的支持下,美国糖尿病、消化病和肾脏病研究所（NIDDK）于2007年12月4～5日在马里兰洲的贝斯达（Bethesda）举行了有关急性肝衰竭（ALF）认识和处置的研讨会。会议认为：ALF是一种少见而难治的临床综合征;其病因多样,在15％的成人患者和50％的儿童患者中不能明确具体病因。ALF病程不定,病死率高。     

Acute liver failure in children

Acute liver failure (ALF) in children differs from that observed in adults in both the etiologic spectrum and the clinical picture. Children, particularly very young ones, do not demonstrate classical features of encephalopathy and the definition of ALF has been revised to include patients with advanced coagulopathy, regardless of mental status. A significant number of these children will go on to require transplant or die. Etiologies vary by age with metabolic and infectious diseases prominent in the first year of life and acetaminophen overdose and Wilson's disease occurring in adolescents. In almost 50% of cases, however, the child has an indeterminate cause for ALF. Management requires a multidisciplinary approach and is directed at establishing the etiology where possible and monitoring, anticipating, and managing the multisystem complications that occur in children with ALF. Overall, short-term outcomes are better in children than adults but are dependent upon the degree of encephalopathy and diagnosis.     

Acute liver failure in children

The management of children with acute liver failure mandates a multidisciplinary approach and intense monitoring. In recent years, considerable progress has been made in developing specific and supportive medical measures, but clinical studies have mainly concerned adult patients. There are no specific medical therapies, except for a few metabolic diseases presenting with acute liver failure. Liver transplantation still remains the only definitive therapy in most instances. Recent clinical studies suggest that hepatocyte transplantation may be useful for bridging patients to liver transplantation, for providing metabolic support during liver failure and for replacing liver transplantation in certain metabolic liver diseases.     

Acute liver failure due to enalapril

This report presents a 46-year-old man who was treated for hypertension with the angiotensin-converting-enzyme (ACE) inhibitor enalapril. After 3 years of continuous treatment he presented with jaundice and progressive liver failure that continued despite withdrawal of the medication. The patient was taking no other medication. All known causes of acute liver failure could be excluded indicating a drug-induced liver damage after long-term treatment with enalapril. Analysis of liver biopsies revealed a pathomorphological pattern comparable to than observed in severe halothane hepatitis. Serological studies including T-cell stimulation with enalapril and a broad spectrum of tests for autoimmunity including autoantibodies against calreticulin, the major Ca2+ and Zn2+ binding protein of the endoplasmic reticulum and suggested to be involved in the pathogenesis of halothane hepatitis were negative. Thus, the mechanism of enalapril-induced liver injury remains obscure. Liver failure progressed and finally led to orthotopic liver transplantation. To our knowledge, this is the longest duration of chronic treatment with an ACE inhibitor before liver failure occurred. In addition, liver failure progressed despite withdrawal of the medication. It is concluded that even after long-term treatment with an ACE inhibitor liver failure may be induced. Therefore, regular monitoring of liver enzymes should be considered.     

Acute liver failure revealing aorto-caval fistula

We report the case of a 49-year-old woman with an aorto-caval fistula following lumbar diskectomy. Initial symptoms included isolated hepatalgia, and were later associated with jaundice and hepatomegaly, suggesting acute liver failure due to right heart failure. Only 9 previous cases of postoperative aorto-caval fistula have been reported and our case emphasizes the possibility of a pseudo-digestive presentation of high output arteriovenous fistula.     

Acute liver failure due to drugs

Acetaminophen overdose and idiosyncratic drug-induced liver injury (DILI) are the most commonly identified causes of acute liver failure (ALF) in the United States. Suspected acetaminophen hepatotoxicity can be effectively treated with N-acetylcysteine but still an estimated 500 patients die each year. Product labeling changes, dispensing restrictions, and reformulation of acetaminophen containing narcotic analgesics have been proposed to reduce the rising incidence of this preventable form of dose-dependent liver injury. In contrast, idiosyncratic DILI is not preventable due to our lack of understanding of host susceptibility and outcome factors. Patients with ALF due to DILI are difficult to diagnose and have a low likelihood of spontaneous recovery. Patients with severe idiosyncratic DILI should be urgently referred to a transplant center as there are no established medical treatments beyond drug discontinuation. Investigation of host variability in metabolic, regeneration, and immunological pathways may provide insights into the molecular basis of DILI as well as improved diagnostic and prognostic biomarkers.