Acute liver failure (ALF) is a complex clinical syndrome characterized by elevated liver biochemistry, coagulopathy, and hepatic encephalopathy without underlying chronic liver disease. The most frequently used classification is the one that O'Grady and collaborators proposed which divides liver failure into 3 categories based on the interval between the development of jaundice and the onset of encephalopathy as hyperacute liver failure (within 7 days), acute (interval of 1 to 4 weeks ) and subacute (5 to 12 weeks).
The most common etiology of acute liver failure in the U.S. and Western Europe is drug-induced liver injury, while in developing countries it is still viral hepatitis. In the United States, about 2800 cases per year of ALF are identified, with acetaminophen being the main cause. Regarding viral hepatitis, hepatitis A and hepatitis E are frequent causes. Over 1.5 million hepatitis A infections occur worldwide, but less than 1% of them progress to ALF. Better sanitary conditions and the use of the hepatitis A vaccine has led to a decrease in the incidence of acute hepatitis A in developed countries. Hepatitis B is responsible for most of the severe viral ALF cases. Hepatitis C does not appear to cause acute liver failure. Hepatitis D infection can lead to acute liver failure in patients with hepatitis B virus co-infection. Hepatitis E is a rare cause of ALF in the USA but represents around a 20 to 40% of ALF cases in developing countries. Herpes simplex virus (HSV) infection is an uncommon cause of ALF. However, if untreated it carries a mortality rate of 80%. The most commonly affected are immunocompromised and pregnant women. Epstein-Barr virus-related ALF is very rare (less than 1% of all ALF cases). Cytomegalovirus is the causal agent of a variety of disease syndromes, including hepatitis. The incidence is low, 19 in 100000 in the general population. Amanita phalloides is the mushroom that most frequently causes hepatotoxicity. Another frequent cause in patients in intensive care is ischemic hepatitis, which occurs when there is a reduction in blood flow and consequently hypoperfusion of hepatocytes leading to liver cell injury. ALF can also result from specific liver diseases of pregnancy as acute fatty liver of pregnancy and HELLP syndrome. Also, Budd-Chiari syndrome, malignancy, and Wilson’s disease can lead to ALF.
The annual incidence of acute liver failure is less than 10 cases per million population in the developed world. In the United States, there are about 2800 cases of ALF per year. The condition is more frequent in developing countries and often affects young people.
The pathophysiology will depend on the etiology of acute liver failure. Liver failure occurs due to massive hepatocyte necrosis and/or apoptosis. The mechanism of necrosis characteristically demonstrates ATP depletion, cerebral edema, mitochondrial depolarization, and cell membrane rupture. However, in apoptosis, there is a preservation of ATP with activation of caspases, chromatin condensation, DNA degradation and reabsorption of cellular components.
If the initial evaluation involves a thorough history and examination, a liver biopsy is rarely necessary (usually a transjugular technique is used).
The initial clinical presentation will depend on the etiology of acute liver failure and the time of evolution from the onset of the disease. Signs and symptoms of acute liver failure may include:
The diagnosis of acute liver failure should start with the history and physical examination followed by laboratories tests and abdominal imaging.
History of prior episodes of jaundice, medication and alcohol use, family history of liver disease, risk factors for acute viral hepatitis are clinically relevant.
Laboratory evaluation is required to establish the cause and evaluate the severity. It should include liver blood tests, INR, renal function, metabolic panel, blood count, viral hepatitis serologies and HIV serology, toxicology screen and acetaminophen level, autoimmune markers and arterial blood gas. Ceruloplasmin level should be required when Wilson disease is suspected. In patients with acute or chronic hepatitis, HBV anti-hepatitis D virus antibodies should be requested. In addition, anti-hepatitis E virus antibodies ordered when there is a history of travel to endemic areas. Abdominal imaging evaluation includes studies ultrasonography to rule out underlying chronic liver disease/cirrhosis.
Acute liver failure is a complex syndrome, and these patients often succumb to its complications. Patient must be managed in the intensive care unit and transferred to a center with a liver transplant facilities. Treatment should commence as soon as possible along with the diagnostic workup. The therapy must address the underlying cause; for example, administer N-acetylcysteine (NAC) for acetaminophen poisoning, antivirals for acute hepatitis B, steroids for autoimmune flare-ups, penicillamine in Wilson disease, and penicillin in mushroom poisoning. NAC has also shown benefit in non-acetaminophen acute liver failure. The mainstay of treatment of ALF is to prevent cerebral edema regardless of etiology; to achieve this one can employ head elevation, mannitol, hyperventilation, and cerebroprotective measures. Few patients need monitoring of intracranial pressure (ICP) with pressure monitors. Other complications include metabolic acidosis, coagulopathy, hypoglycemia, and renal failure. Coagulopathy should only be corrected if there is active bleeding or the patient needs an invasive procedure. In a patient with renal failure, the institution of early renal replacement therapy is necessary. Hypoglycemia is detrimental in patients with ALF and should be prevented by dextrose infusion. Role of prophylactic antibiotics is still controversial. The management of ALF is with aggressive supportive measures to avoid multiorgan failure until there is recovery or liver transplant.
Survival has improved over time with advances in transplant, as identified in an American registry. In 2012 a European registry showed current rates of survival after transplantation of 79% at 1 year and 72% at 5 years. Several clinical factors have prognostic significance in ALF. The presence of encephalopathy is a key indicator, with special attention given to the patient's age and the severity of liver injury, as evaluated by the presence of coagulopathy or jaundice. The most commonly used system for prognosis of ALF prognosis is The King's College Criteria.
Bioartificial liver systems: Various devices have been created to replace or support liver function. They function as a bridge to transplant. However, these are still in the clinical trial phase.
The use of transplanted hepatocytes infused in the peritoneal cavity or the splenic or hepatic portal system is also under investigation.
High-volume plasma exchange (exchange of 8 to 15% of ideal body weight with fresh frozen plasma), is also treatment under study as a liver support system.
Orthotopic liver transplantation remains the only definitive therapy for patients with irreversible liver injury, with a 5-year survival of more than 70%. The majority of deaths are secondary to neurological complications or sepsis and occur in the first 3 months after transplantation. In Asia, living-related liver transplant (LDLT) is common, with reduced waiting time, and offering better outcomes compared to transplant from a deceased donor. Data from Asia have shown right lobe LDLT improves survival in ALF patients. More frequently, in acute cases, ABO-incompatible grafts are being used. However, in these patients, the graft survival is low (30 to 60% 1-year survival). Auxiliary liver transplant retains the recipient's liver and uses a partial lobe of the donor's liver as temporary liver support. Auxiliary liver transplant has a survival of 60 to 65%.
We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.
This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.
Click Your Answer Below
Would you like to access teaching points and more information on this topic?
Click Your Answer Below
Would you like to access teaching points and more information on this topic?
|Lee WM,Squires RH Jr,Nyberg SL,Doo E,Hoofnagle JH, Acute liver failure: Summary of a workshop. Hepatology (Baltimore, Md.). 2008 Apr; [PubMed]|
|Lee WM,Stravitz RT,Larson AM, Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. Hepatology (Baltimore, Md.). 2012 Mar; [PubMed]|
|O'Grady JG,Schalm SW,Williams R, Acute liver failure: redefining the syndromes. Lancet (London, England). 1993 Jul 31; [PubMed]|
|Reuben A,Koch DG,Lee WM, Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology (Baltimore, Md.). 2010 Dec; [PubMed]|
|Wasley A,Fiore A,Bell BP, Hepatitis A in the era of vaccination. Epidemiologic reviews. 2006; [PubMed]|
|Zhang W,Chen B,Chen Y,Chamberland R,Fider-Whyte A,Craig J,Varma C,Befeler AS,Bisceglie AM,Horton P,Lai JP, Epstein-Barr Virus-Associated Acute Liver Failure Present in a 67-Year-Old Immunocompetent Female. Gastroenterology research. 2016 Oct; [PubMed]|
|Fontana RJ,Engle RE,Scaglione S,Araya V,Shaikh O,Tillman H,Attar N,Purcell RH,Lee WM, The role of hepatitis E virus infection in adult Americans with acute liver failure. Hepatology (Baltimore, Md.). 2016 Dec; [PubMed]|
|Flewett TH,Parker RG,Philip WM, Acute hepatitis due to Herpes simplex virus in an adult. Journal of clinical pathology. 1969 Jan; [PubMed]|
|Parekh J,Matei VM,Canas-Coto A,Friedman D,Lee WM, Budd-chiari syndrome causing acute liver failure: A multicenter case series. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2017 Feb; [PubMed]|
|Hanamornroongruang S,Sangchay N, Acute liver failure associated with diffuse liver infiltration by metastatic breast carcinoma: A case report. Oncology letters. 2013 Apr; [PubMed]|
|Panackel C,Thomas R,Sebastian B,Mathai SK, Recent advances in management of acute liver failure. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2015 Jan; [PubMed]|
|Punzalan CS,Barry CT, Acute Liver Failure: Diagnosis and Management. Journal of intensive care medicine. 2016 Dec; [PubMed]|
|Bilir BM,Guinette D,Karrer F,Kumpe DA,Krysl J,Stephens J,McGavran L,Ostrowska A,Durham J, Hepatocyte transplantation in acute liver failure. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2000 Jan; [PubMed]|
|Jensen KO,Angst E,Hetzer FH,Gingert C, Acute Cytomegalovirus Hepatitis in an Immunocompetent Host as a Reason for Upper Right Abdominal Pain. Case reports in gastroenterology. 2016 Jan-Apr [PubMed]|
|Chung RT,Stravitz RT,Fontana RJ,Schiodt FV,Mehal WZ,Reddy KR,Lee WM, Pathogenesis of liver injury in acute liver failure. Gastroenterology. 2012 Sep [PubMed]|
|Maher SZ,Schreibman IR, The Clinical Spectrum and Manifestations of Acute Liver Failure. Clinics in liver disease. 2018 May [PubMed]|
The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of NP-Adult Acute Gerontology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.
StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for NP-Adult Acute Gerontology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in NP-Adult Acute Gerontology, you will already be prepared.
Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of NP-Adult Acute Gerontology. When it is time for the NP-Adult Acute Gerontology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study NP-Adult Acute Gerontology.