AcuteAcute Liver FailureAcuteAcute Liver Failure

Defenition

Etiology

Pathology

Clinical symptoms

LABs

Management

Defenition

Etiology

Pathology

Clinical symptoms

LABs

Management

Definition Definition

1. Biochemical evidence of acute liver injury

(< 8 wks duration)

2. No evidence of chronic liver disease

3.Coagulopathy ( PT>15sec, INR > 1.5 not corrected by vit K, or PT > 20 sec or INR >2)

1. Biochemical evidence of acute liver injury

(< 8 wks duration)

2. No evidence of chronic liver disease

3.Coagulopathy ( PT>15sec, INR > 1.5 not corrected by vit K, or PT > 20 sec or INR >2)

Acute Hepatic Failure-CharacteristicsAcute Hepatic Failure-Characteristics

Impairment of liver functions, jaundiceImpairment of liver functions, jaundice

Encephalopathy

Coagulopathy

Impairment of liver functions, jaundiceImpairment of liver functions, jaundice

Encephalopathy

Coagulopathy

FHFFHF

According to time-length between first signs According to time-length between first signs of liver disease and development of of liver disease and development of encephalopathyencephalopathy

Fulminant = acute liver disease with encephalopathy within 8 weeks of first sign of liver disease.

Acute = up to 28 days

Subacute = 5-12 weeks

According to time-length between first signs According to time-length between first signs of liver disease and development of of liver disease and development of encephalopathyencephalopathy

Fulminant = acute liver disease with encephalopathy within 8 weeks of first sign of liver disease.

Acute = up to 28 days

Subacute = 5-12 weeks

Chronic hepatic failure

Acute on chronic hepatocellular failure

Chronic hepatic failure

Acute on chronic hepatocellular failure

Etiology - CauseEtiology - Cause

Neonate

Infectious - Herpesvirus, echovirus, adenovirus, HBV

Metabolic - Galactosemia, tyrosenemia, neonatal hemochromatosis, mitrochondrial disease, alpha-antitrypsin deficiency

Neonate

Infectious - Herpesvirus, echovirus, adenovirus, HBV

Metabolic - Galactosemia, tyrosenemia, neonatal hemochromatosis, mitrochondrial disease, alpha-antitrypsin deficiency

Older children Older children

Infection - HAV, HBV, Hep D and E, Herpes virus, sepsis, Dengue virus, Leptosirosis

Drugs - valproate, alcohol, isoniazid, acetaminophen, carbamazepine, halothane, ketoconazole and herbal supplement

Infection - HAV, HBV, Hep D and E, Herpes virus, sepsis, Dengue virus, Leptosirosis

Drugs - valproate, alcohol, isoniazid, acetaminophen, carbamazepine, halothane, ketoconazole and herbal supplement

Toxin - Amanita phalloides, carbon tetrachloride, phosphorus

Metabolic - Hereditary fructose intolerance, Wilson’s disease

Autoimmune - Autoimmune hepatitis, Reye’s syndrome

Hepatic ischemia - hepatic vascular occlusion, congenital heart failure, circulatory shock,

Toxin - Amanita phalloides, carbon tetrachloride, phosphorus

Metabolic - Hereditary fructose intolerance, Wilson’s disease

Autoimmune - Autoimmune hepatitis, Reye’s syndrome

Hepatic ischemia - hepatic vascular occlusion, congenital heart failure, circulatory shock,

CURRENT Diagnosis & Treatment: Pediatrics http://accessmedicine.com/content.aspx?aID=6584425 CURRENT Diagnosis & Treatment: Pediatrics http://accessmedicine.com/content.aspx?aID=6584425

Indications for Liver Transplantation in ChildrenIndications for Liver Transplantation in Children

50% Biliary Atresia50% Biliary Atresia

20% Metabolic Diseases (Wilson, Tyrosinemia)

10-15% cirrhosis secondary to viral’ metabolic disease

13% fulminant hepatic failure

2% acetaminophen overdose

50% Biliary Atresia50% Biliary Atresia

20% Metabolic Diseases (Wilson, Tyrosinemia)

10-15% cirrhosis secondary to viral’ metabolic disease

13% fulminant hepatic failure

2% acetaminophen overdose

PathologyPathology

Liver biopsy reveals patchy or confluent massive necrosis of hepatocytes

Multilobuar or bridging necrosis -> collapse of reticulin framework

Zonal pattern necrosis ->acetaminophen, circulatory shock

Microvesiculat fatty infiltrate of hepatocyte ->Reye syndrome, B-oxydance defects, tetracycline toxicity

Liver biopsy reveals patchy or confluent massive necrosis of hepatocytes

Multilobuar or bridging necrosis -> collapse of reticulin framework

Zonal pattern necrosis ->acetaminophen, circulatory shock

Microvesiculat fatty infiltrate of hepatocyte ->Reye syndrome, B-oxydance defects, tetracycline toxicity

Signs that Predict Development of FHFSigns that Predict Development of FHF

Bilirubin> 20 mg%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

Bilirubin> 20 mg%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

Ascitis

AST>3000 u/L

Increase of PMN

Decrease of BUN but increasing of serum Ammonia

Respiratory alkalosis

Marked jaundice

Ascitis

AST>3000 u/L

Increase of PMN

Decrease of BUN but increasing of serum Ammonia

Respiratory alkalosis

Marked jaundice

Stages of Hepatic EncephalopathyStages of Hepatic EncephalopathyII IIII IIIIII IV

SymptomSymptomss

Periods of lethargy, Periods of lethargy, euphoria: reversible of euphoria: reversible of day-night sleeping: day-night sleeping: may be alertmay be alert

Drowsiness, Drowsiness, inappropriate inappropriate

behavior, behavior, agitation, wide agitation, wide mood swings, mood swings, disorientationdisorientation

Stupor but Stupor but arousal, confused, arousal, confused,

incoherent incoherent speechspeech

ComaIVa : response to noxious stimuliIVb: no response

SignsSignsTrouble drawing Trouble drawing

figures, performing figures, performing mental tasksmental tasks

Asterixis, fetor Asterixis, fetor hepaticus, hepaticus,

incontinenceincontinence

Asterixis, Asterixis, hyperreflexia, hyperreflexia,

extensor reflexs, extensor reflexs, rigidityrigidity

Areflexia, no asterixis, flaccidity

ElectroencepElectroencephalogramhalogram NormalNormal

Generalized Generalized slowing alpha slowing alpha

wavewave

Markedly Markedly abnormal, abnormal,

triphasic wavestriphasic waves

Markedly abnormal, Markedly abnormal, bilateral slowing bilateral slowing

delta waves electric-delta waves electric-cortical silencecortical silence

Ref: Nelson textbook of pediatric Ref: Nelson textbook of pediatric 18th edition Page. 170418th edition Page. 1704

Classification of Hepatic Encephalopathy Infants/ChildrenRef: Lippincort and wilkin 2007

Classification of Hepatic Encephalopathy Infants/ChildrenRef: Lippincort and wilkin 2007

Grade 1: confused, mood changes

Grade 2: drowsy, inappropriate behavior

Grade 3: stuporous but obeys simple commands or sleepy but arousable

Grade 4A: comatose but arousable with painful stimuli

Grade 4B: deep coma, not arousable with any stimuli

Grade 1: confused, mood changes

Grade 2: drowsy, inappropriate behavior

Grade 3: stuporous but obeys simple commands or sleepy but arousable

Grade 4A: comatose but arousable with painful stimuli

Grade 4B: deep coma, not arousable with any stimuli

Encephalopathy- Mechanisms Encephalopathy- Mechanisms Accumulation of nitrous metabolitesAccumulation of nitrous metabolites

Accumulation of toxic substances

Hypoglycemia

Brain edema

False neurotransmitters

Electrolyte changes

Acidosis

Accumulation of nitrous metabolitesAccumulation of nitrous metabolites

Accumulation of toxic substances

Hypoglycemia

Brain edema

False neurotransmitters

Electrolyte changes

Acidosis

LaboratoryLaboratory

Coagulation factor - PT

CBC

UA

BUN, Cr

Blood glucose

LFT

Coagulation factor - PT

CBC

UA

BUN, Cr

Blood glucose

LFT

CoagulopathyCoagulopathy

Used to be the leading cause of death Used to be the leading cause of death before liver transplantationbefore 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/pathy

Used to be the leading cause of death Used to be the leading cause of death before liver transplantationbefore 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/pathy

Other Complications of FHFOther Complications of FHF

Cerebral EdemaCerebral Edema

= In up to 80% of patients

The leading cause of death

NO PAPILLEDEMA

CT is useful for identification in only 30-60% of patients; rules out bleeding

Cerebral EdemaCerebral Edema

= In up to 80% of patients

The leading cause of death

NO PAPILLEDEMA

CT is useful for identification in only 30-60% of patients; rules out bleeding

Hepatorenal SyndromeHepatorenal Syndrome

Cause unknownCause unknown

Characterized by oliguria, anuria in later stages

ATN or functional renal failure may occur.

Essential to correct hypovolemia to maintain renal perfusion

Hemodialysis

Cause unknownCause unknown

Characterized by oliguria, anuria in later stages

ATN or functional renal failure may occur.

Essential to correct hypovolemia to maintain renal perfusion

Hemodialysis

Complications- InfectionComplications- Infection

Increased susceptibility to infection, due to defect Increased susceptibility to infection, due to defect of opsonization, low complement, impaired PMN of opsonization, low complement, impaired PMN function, need for invasive monitoringfunction, 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

Increased susceptibility to infection, due to defect Increased susceptibility to infection, due to defect of opsonization, low complement, impaired PMN of opsonization, low complement, impaired PMN function, need for invasive monitoringfunction, 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 ComplicationsOther Complications

Hemodynamic instabilityHemodynamic instability

Hypoxia

Acid-base and electrolyte disturbances (=respiratory and metabolic alkalosis)

Hemodynamic instabilityHemodynamic instability

Hypoxia

Acid-base and electrolyte disturbances (=respiratory and metabolic alkalosis)

ManagementManagement

The essentials of management are: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

The essentials of management are: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

On ET tube to prevent aspiration

Reduce cerebral edema by hyperventilation

Supplemental oxygen

Avoid sedative drugs unless on mechanical ventilator

Prophylactic use of antacid, H2 blockers

Lactulose should be given every 2-4 hours

Lactulose syr dilute with 1-3 ml water can be given as a retention enema q 6 hr

On ET tube to prevent aspiration

Reduce cerebral edema by hyperventilation

Supplemental oxygen

Avoid sedative drugs unless on mechanical ventilator

Prophylactic use of antacid, H2 blockers

Lactulose should be given every 2-4 hours

Lactulose syr dilute with 1-3 ml water can be given as a retention enema q 6 hr

Blood sugar checked every 3-6 hoursBlood sugar checked every 3-6 hours

Limit fluids to 60% maintenance unless dehydrated

Maintain normal BP, CVP

Fluids D10-20% - adequate dextrose should be infused (6–8 mg/kg/min) to maintain normal blood glucose and cellular metabolism

3mmol/kg/24h of potassium

Infusion of fresh frozen plasma and platelets to treat clinically significant bleeding

Monitor urine output

Blood sugar checked every 3-6 hoursBlood sugar checked every 3-6 hours

Limit fluids to 60% maintenance unless dehydrated

Maintain normal BP, CVP

Fluids D10-20% - adequate dextrose should be infused (6–8 mg/kg/min) to maintain normal blood glucose and cellular metabolism

3mmol/kg/24h of potassium

Infusion of fresh frozen plasma and platelets to treat clinically significant bleeding

Monitor urine output

Oral antibiotic may be more effective than Oral antibiotic may be more effective than lactulose in lowering serum ammonia levellactulose in lowering serum ammonia level- nonabsorbable antibiotic such as - nonabsorbable antibiotic such as neomycin, metronidazole, gentamycinneomycin, metronidazole, gentamycin

Paracetamol poisoning- N-acetyl cycteine. Paracetamol poisoning- N-acetyl cycteine. Monitor PT/PTT every 12 hours Monitor PT/PTT every 12 hours

Mechanical ventilation: agitation, hypoxia, coma grade 3-4

Oral antibiotic may be more effective than Oral antibiotic may be more effective than lactulose in lowering serum ammonia levellactulose in lowering serum ammonia level- nonabsorbable antibiotic such as - nonabsorbable antibiotic such as neomycin, metronidazole, gentamycinneomycin, metronidazole, gentamycin

Paracetamol poisoning- N-acetyl cycteine. Paracetamol poisoning- N-acetyl cycteine. Monitor PT/PTT every 12 hours Monitor PT/PTT every 12 hours

Mechanical ventilation: agitation, hypoxia, coma grade 3-4

ReferenceReference

Nelson text book of pediatric 18th edition

Pediatric gastrointestinal and liver disease by Deirde Kelly

Nelson text book of pediatric 18th edition

Pediatric gastrointestinal and liver disease by Deirde Kelly