The Natural History of Severe Acute Liver Injury, Am J Gastroenterol. 2017 Sep; 112(9): 1389–1396:
Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death.
All that follows is from the StatPearls chapter above:
Acute liver failure (ALF) is a rare and often heterogeneous presentation of severe liver dysfunction in a patient with otherwise no pre-existing liver disease. Though it has high morbidity and mortality, its overall survival has improved through intensive care management and emergency liver transplantation advancements. A high index of suspicion, early referral to a specialist liver transplantation center, and adequate supportive management remain the cornerstone for the management of ALF. Future better understanding and knowledge of the pathophysiology of liver injury and management of multi-organ failure will help improve outcomes.
ALF is defined as the development of severe acute liver injury with encephalopathy and impaired synthetic function (INR of 1.5 or higher) in a patient without cirrhosis or preexisting liver disease and with an illness of fewer than 26 weeks duration.
An extensive workup for the etiology of ALF is recommended, as this guides directed therapy and helps determine the outcome. Viral hepatitis and drug-induced hepatitis are the 2 most common causes of ALF worldwide. Other causes include hypoxia-induced liver injury, acute Budd-Chiari syndrome, veno-occlusive disease, Wilson disease, mushroom ingestion, sepsis, autoimmune hepatitis, acute fatty liver of pregnancy, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, heatstroke, and malignant infiltration (with metastasis from breast cancer, small cell lung cancer, and lymphoma) of the liver.
Drug-induced hepatitis accounts for almost half the cases of ALF in the United States, of which acetaminophen is the most common cause. Acetaminophen toxicity is dose-dependent. Drug-induced hepatotoxicity could be idiosyncratic, but this is usually rare. Unintentional ingestion of acetaminophen-induced hepatoxicity leading to liver failure is more common in patients with concomitant alcohol abuse and malnourishment.
Hepatitis A and E are the leading causes of liver failure, most of which are reported from developing countries. Hepatitis B infection could cause liver failure from both acute infections, as well as, from reactivation of hepatitis B following initiation of immunosuppressive therapy. Co-infection with both hepatitis B and C could lead to ALF, although it is rarely seen with hepatitis C alone. Other viral etiologies of ALF include herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Parvoviruses, adenovirus, and varicella-zoster virus.
Please review the rest of this brief but outstanding chapter on the web page starting with the section on etiology.