let's talk about acute liver failure first we will review the clinical definition then we will create a framework for identifying the etiology next we will review treatment principles and finally identify potential complications and interventions to mitigate risk let's start with the clinical definition of acute liver failure the diagnosis of acute liver failure should be considered in any patient with clinical or laboratory evidence of acute liver injury or hepatitis put more simply elevated lft should trigger further evaluation next there must be evidence of coagulopathy defined as an inr greater than or equal to 1.5 next the patient must be encephalopathic the westhaven criteria are utilized to grade hepatic encephalopathy or he the westhaven criteria grade h e on a one through four scale grade 1he is defined by subtle behavioral changes and alteration of the sleepwake cycle grade 2he is defined by the onset of asterixis a form of negative myoclonus defined by transient loss of postural tone as well as lethargy and disorientation grade 3he is defined by more severe confusion disorientation and somnolence finally grade four is defined by coma why are these grades important to recognize in a patient with acute liver failure the answer cerebral edema incidence cerebral edema is rarely observed in patients with grade 1 and 2 he however the incidence increases to 25 to 35 percent in patients with grade 3 and 65 to 75 percent in patients with grade 4. we will talk about cerebral edema in more detail later in the video in order to diagnose acute liver failure all of these abnormalities must be occurring in a patient without pre-existing cirrhosis and with an illness course of less than 26 weeks duration notable exceptions to the 26 week rule include wilson disease reactivation of hepatitis b virus and autoimmune hepatitis next let's create a framework for identifying the etiology of acute liver failure we will use the framework to help guide our initial workup we can break down causes of acute liver failure into two major categories vascular and parenchymal let's start with the vascular category patients can develop acute hepatic vein thrombosis known as the bud chiari syndrome bud chiari syndrome is often associated with polycythemia malignancy and other pro-thrombotic states in addition ischemic damage to the liver from low-flow arterial states can lead to failure this is often referred to as shock liver in this case the acronym shock can be utilized septic hypovolemic or hemorrhagic obstructive cardiogenic and combos of any of the above we work up the vascular causes by obtaining an ultrasound of the liver with dopplers and assessing for various shock states with broad cultures and a transthoracic echocardiogram next let's discuss the parenchymal causes of acute liver failure the parenchymal causes can be further subdivided into five categories tox viral autoimmune infiltrative and pregnancy let's go through these one by one the leading cause of acute liver failure in north america is acetaminophen overdose accounting for approximately 45 percent of cases typical ingestions causing failure exceed 10 grams per day but failure can occur with doses as low as 4 grams per day the second most common cause is drug induced from any number of drugs and supplements additional toxicologic causes include cocaine alcohol and the amanita phalloides or death cap mushroom to work up toxicologic etiologies we obtain an acetaminophen level urine and serum toxicology screen and perform a thorough medication and supplement review if possible including a review of the liver tox online database of the viral etiologies hepatitis a b d and e all cause acute liver failure of note hep c alone does not appear to cause acute liver failure hepatitis b virus is most common in the usa accounting for approximately eight percent of cases hep e is a more frequent cause in endemic areas russia pakistan mexico and india additional viral etiologies include hsv vzv cmv and ebv to work up viral etiologies we obtain the serology shown below the most common autoimmune etiology is autoimmune hepatitis we evaluate for autoimmune hepatitis by obtaining an a a anti-smooth muscle antibody anti-lkm antibody and immunoglobulins as igg is often elevated infiltrative etiologies include wilson disease hemophagocytic lymphohistiocytosis hlh and malignancy wilson disease is suggested by a history of hepatic neurologic and psychiatric abnormalities on lfts a ratio of total bilirubin to alkaline phosphatase greater than 2 may be suggestive to work up infiltrative etiologies we obtain a ceruloplasmin ferritin and additional imaging if necessary pregnancy-associated etiologies include acute fatty liver of pregnancy and help syndrome a urine and serum beta hcg should be obtained overall ischemia acetaminophen drug induced hepatitis b virus and autoimmune hepatitis account for approximately 80 percent of acute liver failure cases in the usa once we have diagnosed acute liver failure and initiated the workup we transition to the most important aspect treatment all patients with acute liver failure should be managed in an icu at a transplant center with a gi or hepatology console in the icu patients should receive standard evidence-based airway management and respiratory support fluid resuscitation and cardiovascular support in addition all patients should receive n-acetylcysteine or neck a 2009 placebo-controlled rct by lee at all randomized 173 patients with acute liver failure without clinical or historical evidence of acetaminophen overdose to either knack infusion or placebo for 72 hours while overall survival at three weeks was similar for both groups patients in the nac group had a higher transplant free survival at three weeks compared to placebo 40 percent versus 27 percent notably this benefit was only observed in patients with grade 1 and 2 hepatic encephalopathy therefore patients with both acetaminophen induced and non-acetaminophen-induced acute liver failure should receive knack on presentation discontinuation of the medication is guided by gi or hepatology next a cyclovir is often initiated until hsv and vzv infection can be ruled out finally and perhaps most importantly it is imperative that we be prepared to manage potential complications of acute liver failure we will use this table to identify the major functions of the liver what happens when the liver fails how we monitor for potential complications and interventions to mitigate risk first the liver converts ammonia into urea for excretion when the liver fails ammonia levels increase ultimately hyperemonemia leads to astrocyte swelling within the brain if severe enough this process leads to cerebral edema and intracranial hypertension ich and ultimately herniation cerebral edema and its complications are a common cause of death in acute liver failure for patients with acute liver failure the serum ammonia concentration correlates with the risk of intracranial hypertension patients with ammonia levels less than 75 rarely develop ich greater than 100 is a risk factor for high grade hepatic encephalopathy and greater than 200 predicts the development of ich we can monitor for cerebral edema with q1 hour neuro checks and ct of the head for any acute changes in mental status we mitigate the risk of cerebral edema by elevating the head of the bed to 30 degrees keeping a net even fluid balance via crrt if necessary and allowing for hyperventilation in addition we can induce hypernatremia to 145 to 155 with hypertonic saline to decrease water entry into astrocytes and brain cells finally mannitol can be administered if there is concern for herniation second the liver stores glycogen and is a major site of gluconeogenesis when the liver fails hypoglycemia may develop we monitor for hypoglycemia with frequent blood glucose checks we treat hypoglycemia with a dextrose infusion third the liver synthesizes clotting factors with the exception of factor eight which is produced by endothelial cells and synthesizes anticoagulants protein c and s when the liver fails patients are at increased risk for both bleeding and clotting as the inr may not be an accurate reflection of overall coagulopathy the functional coagulation status of patients with acute liver failure is best monitored with a thromboelastogram or teg coagulopathy should not be corrected unless bleeding occurs or an invasive procedure needs to be performed all patients with acute liver failure should receive stressors or prophylaxis with either an h2 receptor antagonist or proton pump inhibitor as well as thromboembolic prophylaxis with either low molecular weight heparin or unfractionated heparin finally a healthy liver decreases our risk of infection the kuffer cell a liver macrophage plays a key role in innate immunity when the liver fails patients are at increased risk for infection patients should be cultured on initial presentation and any time there is concern for infection all known infections should be treated aggressively in addition we should have a low threshold for empiric antibiotics if the patient decompensates or the source is unknown in this video we reviewed the clinical definition of acute liver failure elevated lfts plus coagulopathy plus encephalopathy in a patient without pre-existing cirrhosis and an illness course less than 26 weeks we then created the vascular versus parenchymal framework for identifying the etiology then we reviewed treatment principles including the importance of transfer to an icu at a transplant center and neck for all patients and finally we discussed potential complications of acute liver failure including cerebral edema hypoglycemia bleeding and clotting and infection shown as an overview of each objective's whiteboard thank you for watching