Acute Hepatic Failure

Dr. Idit Segal December 2003

Acute Hepatic FailureCharacteristics

Impairment of liver functions, jaundice  Encephalopathy  Coagulopathy


FHF- Definitions
= According to time-length between timefirst signs of liver disease and development of encephalopathy  Fulminant= acute liver disease with encephalopathy within 8 weeks of first sign of liver disease.  Acute=up to 28 days  Subaute=5-12 weeks Subaute=5


FHF-Causes


Differs in different areas of the world: in developing countries- more countriesinfections USA- 35% USA- 35% acetaminophen overdose 50% 50% viral UK- 66% UK- 66% acetaminophen overdose 30% 30% HBV

Indications for Liver Transplantation in Children

50% 50% Biliary Atresia  20% Metabolic Diseases (Wilson, 20% tyrosinemia)  10-15% cirrhosis secondary to viral 10-15% metabolic disease  13% fulminant hepatic failure 13%  2% acetaminophen overdose


Indications for Liver Transplantation in FHF



varies in different series * Viral hepatitis 60% NANB-40% 60% NANB-40% HBVHBV- 5% HAV-13% HAV-13% * Drugs- 14% Drugs- 14% * Wilsons disease- 6% disease* Ischemia- 3% Ischemia* Others: metabolic, immune,etc.- 1-2% immune,etc.-

HAV
Risk for developing FHF=0.1-0.4% FHF=0  Risk is higher in adults and in children younger than 5  Remember: 5% of children- negative childrenserology in first days of illness (may be important in search of etiology of FHF)


NANB (Non A Non B)

    

Can cause severe hepatitis DeathDeath-in over 80% 80% 1:18 children in one series survived without transplantation Suggested etiologies: Togavirus, GB virus, TTV, nucleocapsids Important: may be associated with aplastic anemia in children even after transplantation

Drugs
OverdoseOverdose- acetaminophen, antiepileptics (Phenytoin, Valporate), isoniazid, halothan  Some dose-dependent, some doseidiosyncrathic


Signs that Predict Development of FHF

      

Bilirubin> 20 mg% Changes in consciousness Hyperventilation Hypoglycemia Decrease in albumin INR prolongation, decrease in coagulation factors 5,7 Decrease in liver span along with decline in transaminases and increase of bilirubin.

Encephalopathy- Grades
1 Minor disturbances of consciousness or motor function 2 Drowsy but responsive to commands 3 Stuporous but responsive to pain 4 Unresponsive to pain Seizures may appear at any grade

EncephalopathyMechanisms
      

Accumulation of nitrous metabolites Accumulation of toxic substances (scfa) Hypoglycemia Brain edema False neurotransmitters Electrolyte changes Acidosis

EncephalopathyAggravating Factors
        

Gastrointestinal hemorrhage Hypovolemia Potassium depletion Hypoglycemia Uremia Infection Constipation Sedatives and anaesthetics High protein intake

Coagulopathy
   

Used to be the leading cause of death before era of liver transplantation Low levels of coagulation factors 2,7,9,10 High levels of factor 8 Milder coagulopathy may be caused by disturbance of vitamin K absorption (cholestasis). Associated and aggravated by thrombocytopenia/pathia

Other Complications of FHF

Cerebral Edema  =In up to 80% of patients 80%  The leading cause of death  NO PAPILLEDEMA  CT is useful for identification in only 30-60% 30-60% of patients; rukes out bleeding

Hepatorenal Syndrome
 

 

 

Cause unknown Characterized by oliguria, anuria in later stages ATN or functional renal failure may occur. Essential to correct hypovolemia to maintain renal perfusion Dopamine, furosemide, mannitol Hemodialysis or hemofiltration

Complications- Infection


    

Increased susceptibility to infection, due to defect of opsonization, low complement,impaired PMN function, need for invasive monitoring May not be associated with fever May aggravate encephalopathy Endotoxemia may increase liver injury Gram negative organisms or Staph Aureus Remember: the only sign of infection may be deterioration of liver function of encephalopathy

Other Complications
Hemodynamic instability  Hypoxia  Acid-base and electrolyte Aciddisturbances (=respiratory and metabolic alkalosis)


FHF-Management


The essentials of management are: 1. Diagnosis of cause of liver injury and encephalopathy 2. skilled intensive care to minimize aggravating factors and complications until liver function recovers or transplantation can be performed 3. Liver transplantation

Management, Observation
Blood sugar checked every 3-6 hours  Avoid sedatives  Limit fluids to 60% maintenance 60% unless dehydrated  Maintain normal BP, CVP  Fluids D10-20% with 3mmol/kg/24h of D10-20% mmol/kg/24h potassium  Monitor urine output


Management- cont.
   

LactuloseLactulose-to produce 3-4 loose stools per day Cimetidine Vitamin K 1 mg/day Avoid giving FFP- masks liver FFPfunction.Give only in case of bleeding, before transportation Preventive antibiotics: reduces infection episodes but do not improve survival

Management-cont.
Paracetamol poisoning- N-acetyl poisoningcycteine. Monitor PT/PTT every 12 hours  Mechanical ventilation: agitation, hypoxia, coma grade 3-4


Adverse Prognosis in FHF

     

Non A-G ADevelopment of grade 3-4 hepatic coma Coagulopathy: PTT>50, INR>4 PTT>50, INR>4 Decline of TA Bili>16 along with shrinkage Bili>16 of liver Factor 5<15% - death in 85-90% without 15% 85-90% transplantation Cerebral edema/renal failure- 50-70% failure- 50-70% death

Liver Transplantation in Children

Survival dependent on surgical experience& skills  75-90% 1-year survival in 75-90% transplantation for chronic disease  60-65% 1-year survival in FHF 60-65%  Survival after transplantation from cadaver or living-related-donorliving-related-donorsimilar


ELADS- Extra Corporal Liver Assist Device

Hepatoblast transplantation  Capable of synthesis and detoxificantion  Proved improvement in encephalopathy, coagulopathy, ammonia levels  Serves as a bridge to liver transplantation