Question 1 of 10

    Acute Liver Failure

    Marburg virus liver injury[1]

    Acute liver disease is an uncommon disorder characterized by a rapid decline in liver function. Its multiorgan and multisystem involvement results in encephalopathy, altered mental status, and other complications as well.

    Presentation

    Acute liver failure comprises of two types: fulminant liver failure and subfulminant liver failure. The former is defined as the occurrence of encephalopathy within 8 weeks of onset of symptoms (in patients without pre-existing liver disease). Subfulminant liver failure is characterized by a longer duration between symptoms and encephalopathy.

    The clinical picture features a deterioration in mental status, bleeding, purpura, jaundice, and ascites. Nonspecific symptoms include anorexia, malaise, and motor abnormalities. Additionally, fulminant hepatic failure can feature hematemesis or melena due to GI bleeding. A common condition known as fetor hepaticus, which is sweet breath odor, is also a common sign.

    Sequelae of acute liver failure include cerebral edema, seizures, metabolic dysfunction, infection, kidney failure, and hemorrhage. Also, in cases with rapid onset of ascites and abdominal pain, this may indicate hepatic vein thrombosis or Budd-Chiari syndrome.

    Physical exam

    Findings may include right upper quadrant tenderness, smaller liver span, and jaundice. Stigmata associated with chronic liver disease are also common.

    Vital signs may show tachycardia, hypotension, and tachypnea whether in the setting of sepsis or not. Also, patients with cerebral edema exhibit papilledema, bradycardia, and hypertension secondary to elevated intracranial pressure (ICP). These individuals may progress to states such as obtundation or coma.

    Patients with infection may present symptoms related to that such as fever or cough.

    cardiovascular
    Hypotension
    • Vascular: "Shock liver" from extreme hypotension, Budd-Chiari, Veno-occlusive disease 4.[errolozdalga.com]
    • Tachycardia, tachypnea, and hypotension may occur with or without sepsis.[merckmanuals.com]
    • After intitial volume resuscitation, norepinephrine is a recommended vasopressor for those in persistent hypotension.[pulmccm.org]
    • Of importance, fluid replacement for hypotension should be given carefully since these patients are at risk for cerebral swelling .[symptoma.com]
    • Exclusion criteria included previous NAC exposure, pregnancy, sepsis, malignancy, intractable hypotension, or signs of cerebral herniation.[acep.org]
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  • neurologic
    Confusion
    • ALF patients usually present with a group of symptoms including confusion, fever, fatigue, abdomen pain and jaundice.[uwmedicine.org]
    • They may include: Jaundice (yellow skin and eyes) Abdominal pain Nausea Vomiting General malaise Disorientation, confusion, inability to concentrate Sleepiness Acute liver failure may be diagnosed with blood tests, imaging with ultrasound, and biopsy[columbiasurgery.org]
    • You have trouble thinking clearly, or you are confused.[drugs.com]
    • Confusion, abdominal swelling, and abnormal bleeding are also common.[hopkinsmedicine.org]
    • Older children may seem angry, have a hard time falling asleep, be forgetful or confused, or feel drowsy.[cincinnatichildrens.org]
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  • Liver, Gall & Pancreas
    Asterixis
    • On examination, she was confused and had asterixis.[livertox.nih.gov]
    • Liver palms are red and an hepatic flap, also called asterixis, may be present.[patient.info]
    • Grade 1 is defined as altered behavior with euphoria, anxiety, and decreased attention span; grade 2 is marked by disorientation, lethargy or asterixis; grade 3 is associated with marked disorientation, incoherent speech, and somnolence; and grade 4 being[clevelandclinicmeded.com]
    • In older children, signs and symptoms are identical to those in adults but the classical symptoms of asterixis, tremors, and fetor hepaticus are often absent.[em-consulte.com]
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  • Course
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  • Workup

    Individuals with jaundice, bleeding, or alteration in mental status should be suspected of having liver failure. When evaluating a patient for acute liver failure, it is crucial to determine the etiology as the therapy and management depend on the underlying cause. The clinician should ascertain all medications ingested by the patient including prescription and over-the-counter drugs and supplements. The workup further consists of a physical exam and laboratory tests.

    Laboratory tests

    Since acute liver failure may result in multisystem dysfunction, the following studies should be obtained: a complete blood count (CBC), complete metabolic panel (CMP), renal and liver function tests, PT and international normalized ratio (INR), and urinalysis. Upon confirmation of the diagnosis, crucial tests include an arterial blood gas (ABG), amylase, lipase, blood type and screening. Moreover, if an infection in suspected, blood, urine, and ascitic fluid cultures are indicated.

    The findings of the above studies will determine the severity of acute liver disease and the overall clinical picture. Moreover, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are profoundly increased indicating hepatocellular necrosis. Additionally, PT is prolonged and INR is greater than 1.5.

    Also, plasma bilirubin levels are elevated and continue to increase as the disease progresses. In fact, a level above 4 mg/dL is associated with a poor prognosis in acetaminophen toxicity.

    An ABG will reveal any acid-base disturbance. Another serious finding, severe hypoglycemia, may develop secondary to impairment in gluconeogenesis and glycogen production.

    Imaging

    In patients with both altered mental status and coagulopathy, a head CT scan is performed to identify any intracranial bleeding.

    Pathology

    Other Pathologies
    Hepatic Necrosis
    • It has also been referred to as fulminant hepatic failure, acute hepatic necrosis, fulminant hepatic necrosis, and fulminant hepatitis.[uptodate.com]
    • However, acute liver failure from severe hepatic necrosis is an uncommon phenomenon.[petmd.com]
    • necrosis Acute liver failure Acute necrosis of liver Hepatic necrosis, subacute Subacute hepatic necrosis Subacute liver failure ICD-10-CM K72.00 is grouped within Diagnostic Related Group(s) (MS-DRG v 35.0): 441 Disorders of liver except malignancy,[icd10data.com]
    • The condition is also referred to as a fulminant hepatic failure, acute hepatic necrosis, fulminant hepatic necrosis and fulminant hepatitis.[verywell.com]
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  • Biopsy
    Liver Biopsy
    • Liver biopsy is a procedure that has an uncertain role in ALF.[gastro.org]
    • The liver biopsies showed that the children’s livers had high levels of cytotoxic (“cell-killing”) CD8 T cells, confirming that an autoimmune attack was underway.[med.stanford.edu]
    • Diagnostic evaluation: liver biopsy Liver biopsy is not mandatory in the evaluation of DILI.[gi.org]
    • Tests may include: Bloog tests including liver functions tests (LFTs) and tests to measure blood clotting Urine tests X-rays / scans A liver biopsy.[childliverdisease.org]
    • biopsy, the removal of a small amount of tissue from the liver using a needle.[childrens.com]
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  • Laboratory

    Serum
    Hyponatremia
    • Also, severe electrolye abnormalities (hyponatremia, hypophosphatemia, hypokalemia, hypomagnesemia, also metabolic acidosis).[errolozdalga.com]
    • Hypoglycemia, hyponatremia, and metabolic disturbances from renal failure may also require continual attention.[pulmccm.org]
    • Hyponatremia, when present, is usually due to hypervolemia.[clevelandclinicmeded.com]
    • Chronic hyponatremia exacerbates ammonia-induced brain edema in rats after portacaval anastomosis.[mdedge.com]
    • Younger age, development of renal failure, hyponatremia, inflammatory response and the need for hemodynamic support for cardiovascular collapse are additional risk factors associated with the development of intracranial hypertension [ 24 ].[intechopen.com]
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  • Treatment

    Due to the life-threatening nature of the disease, intensive care is paramount [9] [10] [11] [12]. When encephalopathy progresses, securing the airway is the top priority. Additionally, the medical team should remain vigilant about the hemodynamics, metabolic function, and nutritional status. Furthermore, early recognition of complications such as GI bleeding and cerebral edema is very important.

    Airway protection

    Intubation may be necessary for encephalopathic patients. Close monitoring is critical especially in those with worsening mental status. The medical team should be cautious when choosing drugs for intubation and agitation since many cause sedation and make it challenging to monitor the patient's mental status.

    Hemodynamic and metabolic management

    The therapeutic approach targets hemodynamic and metabolic stability as it is for all critically ill patients. Of importance, fluid replacement for hypotension should be given carefully since these patients are at risk for cerebral swelling. In refractory cases, 20 mL/kg of crystalloid is used. In extreme conditions, vasopressors may be necessary.

    Special care should be geared towards preventing hypoglycemia, which occurs frequently in liver failure. This can be done through with intravenous infusion of glucose.

    Acute liver disease is associated with protein breakdown, and therefore, protein should be replaced carefully. Less protein is administered in patients with hyperammonemia or intracranial hypertension.

    CBC, CMP, and coagulation panel should be obtained frequently while LFTs and serum bilirubin are performed daily.

    Infection

    Empiric antibiotics are initiated when the patient demonstrates signs of infection including fever and worsening of hemodynamics, renal function, or mental status. When the cultures' results are obtained, the medications can be altered. If an infection is ruled out, then the antibiotics are discontinued.

    Coagulopathy

    In cases with bleeding or severe coagulopathy, fresh frozen plasma (FFP) is important. However, this product can cause volume overload and accentuate cerebral edema. Moreover, use of FFP prohibits the monitoring of PT, which is a value predictive of poor prognosis.

    Acetaminophen overdose

    Acetaminophen poisoning can be challenging to diagnose but should be suspected in cases with not clear etiology. It is treated with N-acetylcysteine.

    Transplantation

    The ultimate treatment of liver failure is liver transplantation. It is correlated with 1-year survival rate of almost 80%. Hence, it is reserved for those with a prognosis that is worse without a liver transplant.

    Other

    Lactulose can be beneficial in patients with encephalopathy. As for seizures, phenytoin is a good choice.

    Prognosis

    There are factors that can provide predictive insight regarding the prognosis. For example, worse prognosis is associated with: 1) Severe encephalopathy such as with stage 3 or 4, 2) Patient age younger than 10 years, or greater than 40 years old, 3) Prolonged prothrombin time (PT), and 4) etiology such as idiosyncratic drug reactions or Wilson disease.

    The outcome is better if acute liver failure is secondary to acetaminophen toxicity or infection with hepatitis A or B.

    Death rates increase with sequelae such as cerebral edema, adult respiratory distress syndrome (ARDS), coagulopathy, renal failure, and infection.

    The mortality rate of fulminant hepatic failure was higher than 80%, but orthotopic liver transplantation (OLT) has improved survival.

    Complications

    Shock
    • Having survived severe septic shock and ARDS his condition has stabilised when suddenly his LFTs become deranged with ALT increases to 3402 U/L, AST to 5322 U/L, Bilirubin to 65 µmol/L.[intensivecarenetwork.com]
    • Shock 3:204–209 PubMed Google Scholar 151.[link.springer.com]
    • Vascular: "Shock liver" from extreme hypotension, Budd-Chiari, Veno-occlusive disease 4.[errolozdalga.com]
    • R57.9 ICD-10-CM Diagnosis Code R57.9 Shock, unspecified 2016 2017 2018 Billable/Specific Code Applicable To Failure of peripheral circulation NOS liver K72.00 ICD-10-CM Codes Adjacent To K72.00 K71.4 Toxic liver disease with chronic lobular hepatitis[icd10data.com]
    Coma
    • ICD-10-CM Codes › K00-K95 Diseases of the digestive system › K70-K77 Diseases of liver › K72- Hepatic failure, not elsewhere classified › Acute and subacute hepatic failure without coma 2016 2017 2018 Billable/Specific Code K72.00 is a billable/specific[icd10data.com]
    • Liver encephalopathy is also called portal-systemic encephalopathy, hepatic encephalopathy, or hepatic coma.[childrenshospital.org]
    • Symptoms of ALF vary among children but may include jaundice, bleeding and a change in alertness or even a coma.[phoenixchildrens.org]
    • Liver encephalopathy is marked by confusion, disorientation, irritability, sluggishness, drowsiness, insomnia and/or coma.[lahey.org]
    • It may vary from subtle deficit in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV).[en.wikipedia.org]
    Urinary Tract Infection
    • Infections, such as respiratory and urinary tract infections, may occur with acute liver failure.[drugs.com]
    • Respiratory and urinary tract infections and sepsis are common; pathogens can be bacterial, viral, or fungal.[merckmanuals.com]
    Hypoglycemia
    • Hypoglycemia Hypoglycemia in patients with ALF results from decreased glycogenolysis and gluconeogenesis combined with hyperinsulinemia due to decreased hepatic metabolism. 2 Concurrent sepsis may also contribute to hypoglycemia.[vetfolio.com]
    • Hypoglycemia, hyponatremia, and metabolic disturbances from renal failure may also require continual attention.[pulmccm.org]
    • Special care should be geared towards preventing hypoglycemia , which occurs frequently in liver failure .[symptoma.com]
    • Hypoglycemia is treated with continuous glucose infusion (eg, 10% dextrose), and blood glucose should be monitored frequently because encephalopathy can mask the symptoms of hypoglycemia.[merckmanuals.com]
    • Endo – hypoglycemia is very common and severe, due to poor nutrition and impaired hepatic gluconeogenesis.[errolozdalga.com]
    Aspiration Pneumonia
    • Other causes of lung injury in patients with ALF include aspiration pneumonia, intrapulmonary hemorrhage (secondary to DIC), and pulmonary thromboembolism.[vetfolio.com]
    Hypokalemia
    • Also, severe electrolye abnormalities (hyponatremia, hypophosphatemia, hypokalemia, hypomagnesemia, also metabolic acidosis).[errolozdalga.com]
    • Correction of hypokalemia is essential as hypokalemia increases the kidneys' ammonia production, potentially exacerbating encephalopathy.[en.wikipedia.org]
    • Hypokalemia is common, in part because sympathetic tone is decreased and diuretics are used.[merckmanuals.com]
    • ., refeeding syndrome, hyperventilation, or cellular regeneration). 3 Hypokalemia may result secondary to anorexia, vomiting, and/or prolonged use of potassium-deficient intravenous fluids.[vetfolio.com]
    • This in turn causes the kidneys to absorb hydrogen ions in exchange for potassium, thus resulting in hypokalemia.[clevelandclinicmeded.com]
    Metabolic Acidosis
    • Also, severe electrolye abnormalities (hyponatremia, hypophosphatemia, hypokalemia, hypomagnesemia, also metabolic acidosis).[errolozdalga.com]
    • If shock develops, metabolic acidosis can supervene.[merckmanuals.com]
    • This is commonly seen in acetaminophen-induced liver failure and may be associated with a severe metabolic acidosis.[clinicaladvisor.com]
    Hypotension
    • Vascular: "Shock liver" from extreme hypotension, Budd-Chiari, Veno-occlusive disease 4.[errolozdalga.com]
    • Tachycardia, tachypnea, and hypotension may occur with or without sepsis.[merckmanuals.com]
    • After intitial volume resuscitation, norepinephrine is a recommended vasopressor for those in persistent hypotension.[pulmccm.org]
    • Of importance, fluid replacement for hypotension should be given carefully since these patients are at risk for cerebral swelling .[symptoma.com]
    • Exclusion criteria included previous NAC exposure, pregnancy, sepsis, malignancy, intractable hypotension, or signs of cerebral herniation.[acep.org]
    Hyperventilation
    • Sedation should be used to prevent spontaneous hyperventilation.[pulmccm.org]
    • Management involves raising the head of the bed, hyperventilation (low PCO2 à cerebral vasoconstriction), mannitol (hyperosmolar solution and osmotic diuresis leading to plasma hyperosmolarity and hypernatremia), hypertonic saline.[errolozdalga.com]
    • Oxygen is given to ensure its level in the brain, and the patient is hyperventilated to manage carbon dioxide.[uwmedicine.org]
    • To temporarily decrease cerebral blood flow: Mannitol (0.5 to 1 g/kg, repeated once or twice as needed) can be given to induce osmotic diuresis, and possibly brief hyperventilation can be used, particularly when herniation is suspected.[merckmanuals.com]
    Infection
    • Viral infections The prevalence of hepatitis infections all over the world influences the proportion of cases of acute liver failure caused by viral infections.[lecturio.com]
    • Plasma glucose concentration should be monitored and hypertonic glucose administered as needed. [25] Infection [ edit ] Bacterial and fungal infections are common in ALF, with one study demonstrating culture-proven infection in 80% of ALF patients.[en.wikipedia.org]
    • When it does occur, it's most common in hepatitis A and hepatitis B infection.[verywell.com]
    • Further investigations, such as an ultrasound scan, urine cultures, blood cultures or specific tests for infections may be required in individual cases.[ndsr.co.uk]
    • Because signs of infection overlap with those of acute liver failure, infection is likely to be overtreated pending culture results.[merckmanuals.com]
    Hypoxia
    • […] and lymphatic systems, may lead to coagulant (clotting) complications Causes of Liver Failure in Dogs Acute liver failure is most often caused by infectious agents or toxins, poor flow of fluids into the liver and surrounding tissues ( perfusion ), hypoxia[petmd.com]
    • Metabolic upset such as hypoglycaemia , ketoacidosis, electrolyte imbalance, hypoxia, hypercapnia.[patient.info]
    • These causes include: Hepatotoxic drugs, including some antibiotics, analgesics, chemotherapy agents, and anesthetics Infectious agents, such as leptospirosis Biologic toxins, which include Amanita phalloides mushrooms Heat stroke Inability to breathe (hypoxia[wagwalking.com]
    • "Tissue hypoxia during fulminant hepatic failure".[en.wikipedia.org]
    • Persistent acidemia indicates continued hypoxia at the level of the peripheral tissues and may result in multiorgan failure.[vetfolio.com]
    Respiratory Alkalosis
    Cerebral Edema
    • Development of cerebral edema The exact pathophysiological mechanisms responsible for the occurrence of cerebral edema as a devastating complication of ALF are not completely elucidated.[intechopen.com]
    • Sedation to lower cerebral metabolism and hyperosmotic agents to directly reduce cerebral edema are the cornerstones of therapy.[pulmccm.org]
    • Encephalopathy caused by cerebral edema accounts for 20-25% of deaths as a result of acute liver failure.[maryland.ccproject.com]
    • However, this product can cause volume overload and accentuate cerebral edema .[symptoma.com]
    • 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.[surgery.ucsf.edu]
    Acute Tubular Necrosis
    • Thrombocytopenia with or without DIC increases risk of intracerebral bleeding. [6] Kidney failure [ edit ] Kidney failure is common, present in more than 50% of ALF patients, either due to original insult such as paracetamol resulting in acute tubular[en.wikipedia.org]
    • Infections may result in acute tubular necrosis and should be promptly identified and treated.[clevelandclinicmeded.com]
    • Renal disease may occur in cases of ALF due to acute tubular necrosis from ischemic or toxic injury or secondary to infectious or immune-mediated disease. 1-3 Ancillary clinicopathologic testing that may be indicated includes serology for infectious disease[vetfolio.com]
    • Bile pigment nephropathy and acute tubular necrosis in decompensated cirrhotics and acute on chronic liver failure [abstract 248] .[nature.com]
    Hyponatremia
    • Also, severe electrolye abnormalities (hyponatremia, hypophosphatemia, hypokalemia, hypomagnesemia, also metabolic acidosis).[errolozdalga.com]
    • Hypoglycemia, hyponatremia, and metabolic disturbances from renal failure may also require continual attention.[pulmccm.org]
    • Hyponatremia, when present, is usually due to hypervolemia.[clevelandclinicmeded.com]
    • Chronic hyponatremia exacerbates ammonia-induced brain edema in rats after portacaval anastomosis.[mdedge.com]
    • Younger age, development of renal failure, hyponatremia, inflammatory response and the need for hemodynamic support for cardiovascular collapse are additional risk factors associated with the development of intracranial hypertension [ 24 ].[intechopen.com]
    Lactic Acidosis
    • Lactic acidosis occurs predominantly in paracetomol (also known as acetaminophen) overdose .[en.wikipedia.org]
    • Finally, sinusoidal obstruction syndrome and acute fatty liver with lactic acidosis may cause acute liver failure, but clinical features are usually quite different and different medications are typically implicated.[livertox.nih.gov]
    • Other criteria that indicate emergency liver transplantation include a rapid decrease in liver size, seizures, ascites, hepatorenal syndrome, a fibrinogen level 1 g/L, bilirubinemia 400 μmol/L, worsening lactic acidosis, and hyperammonemia 150 mmol/L.[em-consulte.com]
    Gastrointestinal Hemorrhage
    • H2-receptor antagonist in the prevention of acute gastrointestinal hemorrhage in fulminant hepatic failure: a controlled trial.[mdedge.com]
    • The use of gastrointestinal hemorrhage prophylaxis with a histamine-2 (H2) blocker, proton pump inhibitor, or sucralfate is recommended. [24] Nutrition, electrolytes, and metabolic derangements [ edit ] In patients with grade I or II encephalopathy, enteral[en.wikipedia.org]
    • Rimola A, Bory F, Teres J, Perez-Ayuso RM, Arroyo V, Rodes J (1985) Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage.[link.springer.com]
    Disseminated Intravascular Coagulation
    • Although these are sensitive tests they may indicate other causes, such as vitamin K deficiency or disseminated intravascular coagulation.[patient.info]
    • The highest risk of bleeding is seen in patients with thrombocytopenia or disseminated intravascular coagulation.[clinicaladvisor.com]
    • ALF may also be accompanied by increased fibrinogen-degradation products, decreased fibrinogen, and prolongation of PT and APTT and may be clinically indistinguishable from disseminated intravascular coagulation (DIC). 2,3 Complete blood count results[vetfolio.com]
    Liver Failure
    Hyperammonemia
    • Intracranial pressure, cerebral blood flow, and cerebrospinal fluid formation during hyperammonemia in the cat.[link.springer.com]
    • Less protein is administered in patients with hyperammonemia or intracranial hypertension .[symptoma.com]
    • Continuous renal replacement therapy can help mitigate acid-base and metabolic derangements and control hyperammonemia.[pulmccm.org]
    • Hyperammonemia in the brain causes abnormal brain metabolism of glucose, increased glutamine synthesis and increased oxidative stress.[intechopen.com]
    • […] has a central role in the development of ALF-associated encephalopathy. 34,36 In ALF, hepatic extraction and metabolism of ammonia are severely impaired, resulting in systemic hyperammonemia.[vetfolio.com]
    Wilson Disease
    • Because Wilson’s disease has a very low prevalence in the ALF population, there is a great likelihood that any test for Wilson’s disease would have a high negative predictive value but a low positive predictive value.[gastro.org]
    • Metabolic causes include acute fatty liver of pregnancy , HELLP syndrome (hemolysis, elevated liver function tests, and low platelets), Reye syndrome , and Wilson disease .[merckmanuals.com]
    • Metabolic Wilson's disease .[patient.info]
    • Penicillamine can rescue patients with acute presentations of Wilson's disease who have a coagulopathy but are not yet encephalopathic.[clinicaladvisor.com]
    • While the time course that differentiates acute liver failure from chronic liver failure varies between reports, a commonly used cutoff is an illness duration of Acute liver failure may also be diagnosed in patients with previously undiagnosed Wilson[uptodate.com]

    Etiology

    Acute liver failure is more prevalent in developing countries, since hepatitis A, B, and E are leading causes of the condition and they are not particularly prevalent in the industrialized world. However, drug-induced liver damage due to acetaminophen and idiosyncratic drug reactions is the predominant cause of acute liver failure in the United States and Western Europe. In these latter countries, vaccinations and good sanitation practice have resulted in the decline of viral hepatitis infections.

    Other causes

    Primary cardiac or respiratory failure in ill patients can cause ischemic hepatocellular injury, a potential consequence of severe sepsis. This is accompanied by increased serum aminotransferase concentrations [4] [5].

    Causes

    Hypokalemia
    • Also, severe electrolye abnormalities (hyponatremia, hypophosphatemia, hypokalemia, hypomagnesemia, also metabolic acidosis).[errolozdalga.com]
    • Correction of hypokalemia is essential as hypokalemia increases the kidneys' ammonia production, potentially exacerbating encephalopathy.[en.wikipedia.org]
    • Hypokalemia is common, in part because sympathetic tone is decreased and diuretics are used.[merckmanuals.com]
    • ., refeeding syndrome, hyperventilation, or cellular regeneration). 3 Hypokalemia may result secondary to anorexia, vomiting, and/or prolonged use of potassium-deficient intravenous fluids.[vetfolio.com]
    • This in turn causes the kidneys to absorb hydrogen ions in exchange for potassium, thus resulting in hypokalemia.[clevelandclinicmeded.com]
    Metabolic Acidosis
    • Also, severe electrolye abnormalities (hyponatremia, hypophosphatemia, hypokalemia, hypomagnesemia, also metabolic acidosis).[errolozdalga.com]
    • If shock develops, metabolic acidosis can supervene.[merckmanuals.com]
    • This is commonly seen in acetaminophen-induced liver failure and may be associated with a severe metabolic acidosis.[clinicaladvisor.com]
    Hypoxia
    • […] and lymphatic systems, may lead to coagulant (clotting) complications Causes of Liver Failure in Dogs Acute liver failure is most often caused by infectious agents or toxins, poor flow of fluids into the liver and surrounding tissues ( perfusion ), hypoxia[petmd.com]
    • Metabolic upset such as hypoglycaemia , ketoacidosis, electrolyte imbalance, hypoxia, hypercapnia.[patient.info]
    • These causes include: Hepatotoxic drugs, including some antibiotics, analgesics, chemotherapy agents, and anesthetics Infectious agents, such as leptospirosis Biologic toxins, which include Amanita phalloides mushrooms Heat stroke Inability to breathe (hypoxia[wagwalking.com]
    • "Tissue hypoxia during fulminant hepatic failure".[en.wikipedia.org]
    • Persistent acidemia indicates continued hypoxia at the level of the peripheral tissues and may result in multiorgan failure.[vetfolio.com]
    Gastrointestinal Hemorrhage
    • H2-receptor antagonist in the prevention of acute gastrointestinal hemorrhage in fulminant hepatic failure: a controlled trial.[mdedge.com]
    • The use of gastrointestinal hemorrhage prophylaxis with a histamine-2 (H2) blocker, proton pump inhibitor, or sucralfate is recommended. [24] Nutrition, electrolytes, and metabolic derangements [ edit ] In patients with grade I or II encephalopathy, enteral[en.wikipedia.org]
    • Rimola A, Bory F, Teres J, Perez-Ayuso RM, Arroyo V, Rodes J (1985) Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage.[link.springer.com]
    Wilson Disease
    • Because Wilson’s disease has a very low prevalence in the ALF population, there is a great likelihood that any test for Wilson’s disease would have a high negative predictive value but a low positive predictive value.[gastro.org]
    • Metabolic causes include acute fatty liver of pregnancy , HELLP syndrome (hemolysis, elevated liver function tests, and low platelets), Reye syndrome , and Wilson disease .[merckmanuals.com]
    • Metabolic Wilson's disease .[patient.info]
    • Penicillamine can rescue patients with acute presentations of Wilson's disease who have a coagulopathy but are not yet encephalopathic.[clinicaladvisor.com]
    • While the time course that differentiates acute liver failure from chronic liver failure varies between reports, a commonly used cutoff is an illness duration of Acute liver failure may also be diagnosed in patients with previously undiagnosed Wilson[uptodate.com]

    Epidemiology

    In the United States, the incidence of fulminant liver failure is approximately 2000 cases per year. In acute liver failure, drug-induced hepatotoxicity is responsible for more than half of all cases. Specifically, acetaminophen accounts for 42% of these cases while idiosyncratic drug reactions comprise 12%.

    The occurrence of liver failure is observed in all races. Furthermore, a research study in the United States demonstrated that a large percentage was composed of Caucasian people (74%).

    Autoimmune liver disease shows a gender preference towards women.

    As for age, individuals above 40 years old are associated with a worse prognosis.

    Sex distribution
    Age distribution

    Pathophysiology

    The clinical picture of fulminant hepatic failure resembles that of sepsis, which is a state of reduced systemic vascular resistance. The resultant low blood supply to the organs causes further complications. Hence, acute liver failure affects numerous organs and systems.

    Cerebral edema

    Brain involvement includes cerebral edema, which is the predominant cause of morbidity and fatality in acute liver failure [6] [7] [8]. Cerebral edema is probably a consequence of cytotoxic and vasogenic effects. Additionally, increased cerebral perfusion occurs secondarily to cerebral dysregulation, which is a consequence of elevated levels of the vasodilator, nitric oxide.

    Coagulopathy

    Coagulopathy commonly occurs secondarily to the decreased synthesis of the coagulation factors in the liver.

    Acetaminophen toxicity

    Hepatic metabolism of acetaminophen produces a metabolite more toxic than the drug itself.

    Other

    Some of the main features of acute liver failure include hyperbilirubinemia, which usually manifests at initial presentation.

    Hypoglycemia develops as a result of impaired glycogen production and gluconeogenesis.

    Prevention

    Acute liver failure is associated with numerous etiologies. One of the causes, acetaminophen overdose, can be prevented if the dosage guidelines are followed correctly. The same applies to all medications and supplements as well. Additionally, depending on the type of viral hepatitis, an infection can be prevented through vaccinations, implementation of good hygiene, and practicing a safe and healthy lifestyle.

    Summary

    Acute liver disease is the severe deterioration of hepatic function secondary to liver conditions such as hepatitis, cirrhosis, or overdose of acetaminophen and other drugs. In the United States, the predominant cause is drug toxicity, while viral hepatitis is the main etiology in developing regions. It occurs in less than 10 cases per million annually in developed countries. Also, most cases occur in adults in their 30s without previous liver disorders.

    The potentially fatal condition is classified as fulminant or subfulminant in accordance to the interval between the onset of symptoms and development of encephalopathy [1]. Furthermore, acute liver failure results in coagulopathy, altered mental status, and dysfunction of multiple organs and systems [2] [3].

    The diagnosis is determined through a history, physical, exam, and extensive laboratory testing. Since there are dangerous manifestations, it is important to assess the full clinical picture during the workup.

    The initial goal of therapy involves the identification and treatment of the underlying cause. Since acute liver failure is associated with a high mortality rate, these critically ill patients warrant close monitoring. Specifically, there are crucial aspects to consider such as airway protection, maintenance of the hemodynamic and metabolic status, and prompt recognition of complications such as infection, cerebral edema, and gastrointestinal (GI) bleeding.

    Patient Information

    Acute liver failure is a disease in which there is a rapid decline in the perfomance of the liver. It can be caused by liver disease, viral hepatitis, especially hepatitis B, cirrhosis, or poisoning due to alcohol or medications. In fact, acetaminohen overdose is the most common cause of acute liver failure in the United States, whereas viral hepaitis is the most common cause in the developing world.

    When the liver becomes largely damaged, failure occurs. It can occur over days, weeks, months or years.

    The liver is responsible for many functions. So when it becomes damaged, there are many detrimental consequences such as:

    • A substance in the body called bilirubin builds up and therefore, the patient becomes jaundiced
    • The liver cannot synthesize proteins that clot blood. Therefore, the patient can bleed and bruise easily
    • Fluid builds up in the abdomen. This is known as ascites
    • The toxins that build up affects the brain. This results in encephalopathy
    • New blood vessels form in the esophagus and stomach to bypass the liver. These new vessels are fragile, vulnerable and tend to bleed easily.
    • Kidneys lose function
    • Immune system loses function
    • Metabolic dysfunction causes low blood sugar and proteins

    Symptoms include:

    Acute liver disease is diagnosed through the history, physical exam, and important blood tests that check for liver function, electrolytes, liver proteins, and others.

    As soon as it is diagnosed, liver failure is treated promptly to prevent further complications. These patients are admitted to the intensive care unit (ICU).

    Treatment consists of the following:

    • Low blood pressure is treated with intravenous fluids and possibly drugs
    • Encephalopathy is managed with lactulose
    • Bacterial infection is managed with antibiotics
    • Low blood sugar is treated with intravenous sugar

    Other symptoms

    Toxic Liver Disease
    • liver disease with chronic lobular hepatitis K71.5 Toxic liver disease with chronic active hepatitis K71.6 Toxic liver disease with hepatitis, not elsewhere classified K71.7 Toxic liver disease with fibrosis and cirrhosis of liver K71.8 Toxic liver disease[icd10data.com]

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    References

    1. Wlodzimirow KA, Eslami S, Abu-Hanna A,Nieuwoudt M, Chamuleau RA. Systematic review: acute liver failure -- one disease, more than 40 definitions. Alimentary Pharmacology and Therapeutics. 2012; 35(11):1245-1256.
    2. Escorsell A, Mas A, de la Mata M. Acute liver failure in Spain: analysis of 267 cases. Liver Transplantation. 2007; 13(10):1389-1395.
    3. Kumar R, Shalimar, Bhatia V, et al. Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome. Hepatology. 2010; 51(5):1665-1674.
    4. Lescot T, Karvellas C, Beaussier M, Magder S. Acquired liver injury in the intensive care unit. Anesthesiology.2012; 117(4):898-904.
    5. Henrion J. Hypoxic hepatitis. Liver International. 2012;32(7):1039-1052.
    6. Jalan R, Olde Damink SW, Deutz NE, Hayes PC, Lee A. Moderate hypothermia in patients with acute liver failure and uncontrolled intracranial hypertension. Gastroenterology. 2004; 127(5):1338-46.
    7. Lidofsky SD, Bass NM, Prager MC, et al. Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure. Hepatology. 1992; 16(1):1-7.
    8. Detry O, Arkadopoulos N, Ting P, et al. Intracranial pressure during liver transplantation for fulminant hepatic failure. Transplantation. 1999; 67(5):767-70.
    9. Polson J, Lee WM. AASLD position paper: the management of acute liver failure. Hepatology. 2005; 41(5):1179-97.
    10. Stravitz RT, Kramer AH, Davern T, et al. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Critical Care Medicine. 2007; 35(11):2498-508.
    11. Bernal W. Intensive care support therapy. Liver Transpl. 2003; 9(9):15-7.
    12. Jalan R. Acute liver failure: current management and future prospects. Journal of Hepatology. 2005; 42(1):115-23.

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