Acute Liver failure

Acute Liver Failure:
Acute liver failure is characterized by acute liver injury, hepatic encephalopathy, and an elevated PT/INR. It has also been referred to as fulminant hepatic failure, acute hepatic necrosis, fulminant hepatic necrosis, and fulminant hepatitis.
Acute liver failure refers to the development of severe acute liver injury with encephalopathy and impaired synthetic function (INR of ≥1.5) in a patient without cirrhosis or preexisting liver disease. Time course that differentiates acute liver failure from chronic liver failure is <26 weeks i.e. more than 6 months. On the other hand, patients with acute severe alcoholic hepatitis, even if recognized for <26 weeks, are considered to have acute-on-chronic liver failure since most have a long history of heavy drinking.
  • Acetaminophen
  • Drugs like Dilantin, valproate, PCN
  • Viral hepatitis ( Hepatitis, EBV, CMV, HSV, Adeno)
  • Alcoholic hepatitis
  • Ischemic hepatopathy
  • Congestive hepatopathy
  • Budd-Chiari syndrome
  • Veno-occlusive disease
  • Portal vein thrombosis
  • Acute fatty liver of pregnancy/HELLP syndrome
  • Toxins like mushroom poisoning
  • Sepsis
  • Autoimmune hepatitis
  • Wilson disease
  • Reyes syndrome
  • Malignant infiltration
  • Partial hepatectomy
  • Heat stroke
  • Hemophagocytic lymphohistiocytosis (more common in children and adolescents)
Hepatitis C or D virus alone does not appear to be a significant cause of acute liver failure in the absence of co infection with hepatitis B. Also, look for more than one causes of acute liver failure.
Clinical Features:
Signs include hepatic encephalopathy, prolonged prothrombin time (INR ≥1.5), jaundice, hepatomegaly, right upper quadrant tenderness and ascites.. Symptoms may include fatigue/malaise, lethargy, anorexia, nausea and/or vomiting, RUQ pain, pruritus and altered mental status. 
As the liver failure progresses, patients may develop mental status changes (eg, lethargy, difficulty sleeping) and become confused or eventually comatose. In grade 4 encephalopathy, pt. may show decerebrate or decorticate rigidity. Cerebral edema may develop in patients with acute liver failure with hyperammonemia leading to increased intracranial pressure.
Lab abnormalities:
  • Prolonged prothrombin time, resulting in an INR ≥1.5 (this finding is part of the definition of acute liver failure and thus must be present). However, despite an abnormal INR, patients may not be hypocoagulable.
  • Elevated aminotransferase levels (often markedly elevated)
  • Elevated bilirubin level
  • Low platelet count (≤150,000/mm3, though hemostasis when measured by thromboelastography may be normal)
  • Elevated ammonia level
  • Elevated lactate dehydrogenase (LDH) level
  • Elevated WBC with neutrophil predominance in alcoholic hepatitis.
Frequent monitoring of labs (three to four times daily) should be performed for coagulation parameters, complete blood counts, metabolic panels, and arterial blood gasses. In particular, patients should be monitored and treated for hypoglycemia, hypokalemia, hypomagnesemia, and hypophosphatemia. 
Decreasing aminotransferase levels may indicate spontaneous recovery but could also signal worsening liver failure with loss of hepatocyte mass. In patients who are improving, the bilirubin and prothrombin time/international normalized ratio (INR) will improve, whereas in those with worsening liver failure, the bilirubin and prothrombintime/INR will continue to rise.
Patients admitted to hospitals without a liver transplantation program should be transferred as soon as possible, since it can be hazardous to transfer patients later in the disease course because of severe coagulopathy and increased intracranial pressure. Stimulation can lead to increased intracranial pressure and should be minimized.
Hemodynamic derangements are common in patients with acute liver failure due to low systemic vascular resistance. In addition, patients may have intravascular volume depletion because of decreased oral intake and extravasation of fluid into the extra-vascular space. The goal is to maintain a mean arterial pressure of at least 65 mmHg or a cerebral perfusion pressure of at least 50 to 60 mmHg. Norepinephrine is often preferred because it is thought to best augment peripheral organ perfusion with less tachycardia and better preservation of splanchnic blood flow than other agents. Vasopressin may be added in those who do not respond to norepinephrine. As is seen in patients with septic shock, patients with acute liver failure may develop adrenal insufficiency. Thus, if hypotension persists despite volume repletion and vasopressor support, a trial of hydrocortisone is reasonable. Prophylactic administration of fresh frozen plasma to correct coagulopathy is usually not recommended. 
Nutritional support is a vital component in the treatment of acute liver failure and should be initiated early. It is required to prevent catabolism of body stores of proteins and it may decrease the risk of gastrointestinal bleeding from stress ulceration in critically ill patients.
  1. Acetaminophen toxicity — the threshold for giving N-acetylcysteine should be low, because patients with acetaminophen-induced acute liver failure may not have a clear history of acetaminophen overdose. As an example, doses as low as 4 g/day can cause hepatotoxicity in regular alcohol users. Thus, N-acetylcysteine should not only be given to patients with a history suggestive of acetaminophen toxicity, but also for those with acute liver failure of unknown etiology.
  2. Hepatitis B infection — Antiviral therapy with a nucleoside analogue
  3. Mushroom poisoning — Early administration of activated charcoal is recommended.
  4. Budd-Chiari syndrome — Methods to restore hepatic drainage in patients with acute Budd-Chiari syndrome include transjugular intrahepatic portosystemic shunt placement, surgical decompression, or thrombolysis.
  5. Herpes simplex virus infection — Patients with suspected or documented herpes simplex virus infection should receive acyclovir.
  6. Wilson disease — Patients with acute liver failure due to Wilson disease typically require liver transplantation. Plasma exchange to remove copper may be a temporizing measure.
  7. Autoimmune hepatitis — typically treated with glucocorticoids.
  8. Acute fatty liver of pregnancy — there is no specific medical treatment for acute fatty liver of pregnancy. Attempt for delivery soon.
  9. Alcoholic hepatitis:
The Maddrey discriminant function (DF) and the Model for End-stage Liver Disease (MELD) scores are most commonly used to help identify patients who are more likely to benefit from pharmacologic therapy. DF is based on bilirubin and INR. MELD score is based on bilirubin, INR and creatinine.
Patients with a DF value ≥32 have high short-term mortality and may benefit from treatment with glucocorticoids.
The management of alcoholic hepatitis includes treatment for alcohol withdrawal, providing hemodynamic and nutritional support, and in those with severe alcoholic hepatitis (DF ≥32), treating with either a glucocorticoid or pentoxifylline and may use Baclofen to treat for alcohol cravings. Prednisolone 40mg per day for 4 weeks followed by taper over 2 weeks has traditionally been used, although some studies suggest that pentoxifylline 400mg TID is effective and lacks the side effects seen with glucocorticoids. However, pentoxifylline does not appear to be effective in patients who have already failed glucocorticoid therapy. Prednisolone is preferred to prednisone, as the latter requires conversion to Prednisolone. (1mg of Prednisolone = 1mg of prednisone).
  • Hypokalemia
  • Hyponatremia: Tissue hypoperfusion resulting in enhanced release of antidiuretic hormone and impaired renal function combine to limit free water excretion.
  • Hypophosphatemia.  The presence of hypophosphatemia is good prognostic sign. The fall in plasma phosphate is due to movement into the cells and may be related to the metabolic and synthetic demands of a regenerating liver.
  • Hypoglycemia.
  • Hepatic encephalopathy. Can use lactulose to treat it.
  • Cerebral edema and raised ICP. The classic signs of ICP elevation include systemic hypertension, bradycardia, and irregular respirations (referred to as Cushing's triad). Neurologic manifestations may include increased muscle tone, hyperreflexia, and altered pupillary responses.
Rising ammonia concentration in blood, resulting from impaired detoxification to urea by the liver, is the major contributor to cerebral edema in acute liver failure. Ammonia is a neurotoxin and an osmotic agent; sustained ammonia levels of 150 to 200 µmol/L greatly increase intraneuronal osmolarity (through its metabolism to glutamine) and the risk for intracranial hypertension and encephalopathy.  Raised ICP can be treated with hyperosmotic agents like 3%saline, 23%saline but keeping Na<150 or with mannitol, hyperventilation or inducing barbiturate coma. 
Evidence is lacking for routinely placing invasive ICP monitoring devices in all patients with acute liver failure. However, when there is cerebral edema and at risk of herniation, ICP monitoring device is indicated. Transcranial Doppler ultrasound is a noninvasive method that uses the velocity of blood flow in the proximal cerebral circulation and can be used to indirectly estimate ICP. 
  • Seizures. Will be difficult to control with AED’s.
  • Acute renal failure, likely due to hepatorenal syndrome
Model for End-stage Liver Disease (MELD) score — MELD is a prospectively developed and validated chronic liver disease severity scoring system that uses a patient's laboratory values for serum bilirubin, serum creatinine, and the international normalized ratio (INR). Patients with HCC are assigned specific MELD scores based upon tumor burden and the associated predicted three-month survival for HCC, rather than on the traditional MELD parameters (i.e., serum bilirubin, serum creatinine, and INR).

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