Acute Liver Failure (ALF)


Definition:
Pediatric Acute Liver Failure Study Group (PALF) Defines ALF as:
  1. Biochemical evidence of  Liver Injury
  2. no known h/o chronic liver disease
  3. Coagulopathy not due to vit K deficiency (not corrected by Vit K)
  4. INR > 1.5 if the patient has hepatic encephalopathy or >2.0 without encephalopathy
Adult definition is hepatic encephalopathy and coagulopathy within 8wks of onset of liver disease

Etiology
Age 0-3 (unknown in 50%, Metabolic 15%, Viral 8%, autoimmune 4%, Ischemia 4%, Tylenol 3%, Drugs 0.5%, other 12%)
Age 3-18 (unknown 50%, Tylenol 18%, Autoimmune 8%, metabolic 7%,  other 7%, drugs 6%, ischemia 4%)

Presentation: (Varies based on etiology)
Diagnostic Testing (varies based on presentation)

Age prioritized workup

< 3 months of age


3 months to 4 years

5 years to 18 years

Additional diagnostic screening tests to consider directed by history and clinical course
Treatment
  1. Patients with ALF should be hospitalized and monitored frequently, preferably in an ICU
  2. Early consultation with Liver Tranplant center with plans to transfer care as soon as possible
  3. Etiology should be determined to guide further management decisions (treat primary etiology if known)
  4. Specific considerations/complications

Supportive care
  1. Consider transfer to a center able to provide liver transplant
  2. Manage ICP and multiorgan failure while awaiting recovery of liver function or liver transplant
  3. Maintain adequate glucose infusion rate
  4. Electrolyte replacement (correct hypokalemia and hypophosphatemia)
  5. Encephalopathy: medical therapy with lactulose. Minimize sedation, treat sepsis, and lower protein intake. ICP monitoring is controversial. Consider mannitol, hyperventilation, hypothermia, or barbiturate coma for cerebral edema.
  6. Coagulopathy: correct prothrombin time (PT)/INR with fresh frozen plasma or recombinant factor VII only in the setting of active bleeding or in anticipation of an invasive procedure
  7. Prophylactic acid-suppressive therapy
  8. Patients may develop hepatorenal syndrome or acute tubular necrosis and require dialysis or continuous veno-venous hemofiltration
  9. Obtain blood cultures and start antibiotics if indicated (↑ susceptibility to infections)


Cerebral  Edema/Intracranial  Hypertension

Grade I/II Encephalopathy
-Consider transfer to liver transplant facility and listing for transplantation
-Brain  CT:  rule  out  other  causes  of  decreased  mental  status;  little  utility  to identify cerebral edema
-Avoid stimulation; avoid sedation if possible
-Antibiotics: surveillance and treatment of infection required; prophylaxis possibly helpful
-Lactulose, possibly helpful

Grade III/IV Encephalopathy
-Continue management strategies listed above
-Intubate trachea (may require sedation)
-Elevate head of bed
-Consider placement of ICP monitoring device
-Immediate treatment of seizures required; prophylaxis of unclear value
-Mannitol: use for severe elevation of ICP or first clinical signs of herniation
-Hypertonic saline to raise serum sodium to 145-155 mmol/L
-Hyperventilation: effects short-lived; may use for impending herniation

Infection
-Surveillance for and prompt antimicrobial treatment of infection required  (obtain cultures for any clinical deterioration - fever may not be present)
-Antibiotic prophylaxis possibly helpful but not proven

Coagulopathy (decrease in both procoagulant proteins V,VII,X, and fibrinogen and anticoagulant antithrombin, proteins C&S)
-Bleeding is actually relatively rare complication
-Vitamin K: give at least one dose
-FFP: give only for invasive procedures or active bleeding
-Platelets: give only for invasive procedures or active bleeding
-Recombinant activated factor VII: possibly effective for invasive procedures
-Prophylaxis for stress ulceration: give H2blocker or PPI

Aplastic Anemia
-immunomodulatory medications (corticosteroids, cyclosporine A, etc...)
-hematopoetic stem cell transplantation

Hemodynamics/Renal  Failure
-Volume replacement
-Pressor support (dopamine,  epinephrine,  norepinephrine) as needed to maintain adequate mean arterial pressure
-Avoid nephrotoxic agents
-Continuous modes of hemodialysis if needed
-Vasopressin recommended  in  hypotension refractory  to volume  resuscitation and norepinephrine

Ascites
-Can develop in some patients with hypoalbuminemia and excessive fluid administration
-restrict fluid
-diuretics reserved for patients with respiratoryt compromise or generalized fluid overload (aggressive diuresis may lead to hepatorenal syndrome)

Metabolic  Concerns
-Follow closely: glucose, potassium, magnesium, phosphate
-Consider nutrition: enteral feedings if possible or total parenteral nutrition

Detox
plasmapheresis/plasma exchange may be needed to remove suspected toxins from the blood

Liver Transplant
  1. Pediatric ALF (PALF) results in death or liver transplantation in up to 45% of pediatric patients
  2. Patients with ALF are more likely to be critically ill at the time of transplant than most end-stage liver disease recipients and may die from multisystem organ failure or neurologic complicationsa.  Studies show 1-year survival of 80%–90% after liver transplantation
  3. Several scoring systems help predict PALF outcome and the need to proceed with transplantation
  4. The liver injury unit (LIU) scoring system, with LIU = [3.584 × peak total bilirubin (mg/dL)] + [1.809 × peak PT (seconds)] + [0.307 × peak NH3  ammonia (μmol/L)], was found by the PALF study group to be a better predictor of transplant-free survival than other scoring systems. However, making the decision to move forward with transplantation still remains challenging.
  5. In general, progressive encephalopathy, worsening coagulopathy, and worsening cholestasis associated with poor outcome of the native liver
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Grades of Encephalopathy
I   - Changes in behavior with minimal change in level of consciousness
II  - Gross disorientation, drowsiness, possibly asterixis, inappropriate behavior
III - Marked confusion; incoherent speech, sleeping most of the time but arousable to vocal stimuli
IV - Comatose, unresponsive to pain, decorticate or decerebrate posturing