Fulminant Hepatic Failure (FHF)

(Acute Liver Failure {ALF})

Dr / Reyad Alfaky
 Definitions
Fulminant hepatic failure
• Acute severe impairment of liver function
associated with progressive mental changes in
patients who have had liver disease for less
than 8 weeks.
 Definitions Fulminant Hepatic Failure
A. biochemical evidence of acute liver injury or
(usually <8 wk duration) • biochemical ;acute liver
– no evidence of chronic liver disease; injury (usually <8 wk)
and • no evidence of chronic liver
B. hepatic-based coagulopathy defined as : OR disease; and
1. prothrombin time (PT) >15 sec or 1) PT >20 sec
2. international normalized ratio (INR) >1.5 or
3. not corrected by vitamin K in the 2) INR >2
A. presence of clinical hepatic regardless of the presence of
encephalopathy, clinical hepatic
encephalopathy.
 Definitions Late-onset hepatic failure

• development of the hepatic encephalopathy

occurs 8-24 wk from the first sign of liver disease
in patients with pre-existing liver disease
 subfulminant” or “subacute” liver failure

• Rapid deterioration of liver function with the

development of HE within six months
 Definitions
Chronic hepatocellular failure
• The combination of jaundice, and/or ascites
and/or encephalopathy, in varying degrees,
persistent or fluctuant, caused by chronic liver
disease.
 Definitions
Acute on chronic hepatocellular failure
• Acute decompensation in clinical state
produced in patients with chronic liver disease
by precipitants such as sepsis, hemorrhage,
surgery, or sedatives.
 “Recurrent” liver failure
Conditions associated with recurrent PALF include
1. metabolic disease, particularly fatty acid oxidation
defects, and

2. re-exposure to an unsuspected drug or herbal remedy

 epid
• The estimated frequency of acute liver failure (ALF) in
all age groups in the United States is about 17 cases per
100,000 population per year, but the frequency in
children is unknown.
• PALF accounts for 10 to 15 percent of pediatric liver
transplants performed in the United States annually.
 Etiology of FHF
CAUSES OF PEDIATRIC ACUTE LIVER FAILURE:
categorized as
1. infectious,
2. immunologic,
3. metabolic, and
4. toxin or drug-related
 Etiology of FHF
• The etiology of pediatric acute liver failure (PALF) is
1. identified in approximately 55 percent of cases,
2. indeterminate cause in 45 percent
1. Indeterminate cases are likely composed of a number
separate conditions including immune dysregulation, with the
latter condition having a variety of manifestations.
Categories of idiopathic pediatric acute liver failure
 Etiology of FHF
A. Idiopathic form of FHF:
– It accounts for 40-50% of cases in children.
– The disease occurs sporadically and usually without the risk factors
B. Viral hepatitis
– HAV: In endemic areas, HAV constitutes up to 40% of all cases of
pediatric acute liver failure.
C. Autoimmune hepatitis 5% of cases
 Etiology of FHF
D. Toxins, Drugs, and Chemicals
E. Hepatic ischemia and hypoxia
F. Acute extensive infiltration of hepatocytes with
microdroplets of fat ; hemophagocytic lymphohistocytosis
G. Metabolic disorders
H. Hepatotoxic herbal or dietary supplements
 Metabolic diseases lead to acute liver
failure in children
Age Condition
Galactosemia
Niemann-Pick type C
Less than 6 months Tyrosinemia
Glycosylation defect
Mitochondrial disease*
Mitochondrial disease*
Tyrosinemia
7 months to 4 years
Hereditary fructose intolerance
Urea cycle defects
Wilson disease
5 years to 18 years
Mitochondrial disease*
* Mitochondrial disease includes fatty acid oxidation defects, respiratory chain defects, and
 PATHOGENESIS

A. Neurotoxic substances
B. False neurotransmitters
C. Multifactorial causes
D. Massive destruction of hepatocytes
 NEUROTOXIC SUBSTANCES
A. Ammonia
B. Mercaptans
C. fatty acids
D. benzodiazepine like-compounds
E. gammaaminobutyric acid=GABA
 FALSE NEUROTRANSMITTERS

• Impaired capacity of the liver to remove aromatic aminoacids

• promotes the synthesis of

– serotonin and

– false neurotransmitters as octopamine (inhibitory neurotransmitters) at

the expense of true ones as dopamine and norepinephrine (excitatory

neurotransmitters) —> encephalopathy and coma.

 MULTIFACTORIAL CAUSES
• Factor may contribute to its pathogenesis.

A. Hypoglycemia

B. Hypoperfusion

C. Anoxia

D. Electrolyte Disturbances

E. Brain Edema
 PATHOLOGY
A. Liver pathology
1. Massive necrosis of the hepatocytes
2. Mixed inflammatory cell infiltrate is usually present
B. Brain pathology:
– Brain edema
 CLINICAL MANIFESTATIONS
• Patients should be closely observed for hepatic encephalopathy, which is initially
characterized by
1. minor disturbances of consciousness or

2. motor function.

3. Irritability, poor feeding, and a change in sleep rhythm may be the only findings in infants;

4. asterixis may be demonstrable in older children.

5. Patients are often somnolent, confused, or combative on arousal and can eventually become
responsive only to painful stimuli.

6. Patients can rapidly progress to deeper stages of coma in which extensor responses and
decerebrate and decorticate posturing appear.
 STAGES OF HEPATIC ENCEPHALOPATHY
I II III IV
Symptoms Periods of Drowsiness, Stupor but arousable, Coma
lethargy, inappropriate confused, incoherent 1. IVa :
euphoria; behavior, speech •responds to
reversal of day- agitation, wide noxious stimuli
night sleeping; mood swings, 2. IVb :
may be alert disorientation •no response
Signs Trouble drawing Asterixis, Asterixis, Areflexia,
figures, fetor hepaticus, hyperreflexia, no asterixis,
performing incontinence extensor reflexes, flaccidity
mental tasks rigidity
Electroence Normal Generalized Markedly abnormal, Markedly abnormal
phalogram slowing triphasic waves bilateral slowing, d
q waves waves, electric-
cortical silence
 Assessment of Encephalopathy for Young
Children: Birth to Age 3 Years
Clinical Asterixis/ Neurologic Electroencephalographic
Reflexes Signs (h nges
Early (l Inconsolable crying Sleep Unreliable/ UntestaMe Normal or abnormal gener
and II) reversal Inattention to task normal or alized slowing/tnphasic
hyperreflexic waves
Mid (III) Somnolence Stupor Unreliable/ Most likely Abnormal, generalized
Combativeness hypereflexic untestable slowing, triphasic waves
Late (IV) Comatose Absent Decerebrate or Abnormal, very slow,
Arouses with painful stimuli activity
(IVa)
No response (IVb)
approach to the child with acute liver failure
 should include the following:
1. initial stabilization

2. establishment of an accurate diagnosis

3. provision of intense, comprehensive medical supportive therapy

4. anticipation, prevention, and timely treatment of complications.

5. early referral to a liver transplant center, prior to the onset of complications of multiorgan
failure, to assess both for indications and contraindications to liver transplantation.
 INITIAL STABILIZATION/THERAPY
• Assure the airway is patent and ventilation is
adequate.

• Maintain vital signs within normal limits;

• IV fluid administration if indication
 DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE

I. Assess liver function

II. Determined etiology
III. Monitor and detect complication
 DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE
I. General work-up
A. Alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase,
alkaline phosphatase, total and conjugated bilirubin,
B. prothrombin time (INR), PTT,
C. CBC,
D. serum electrolytes, blood urea, creatinine, blood and urine cultures,
E. blood group,
F. chest X-ray, serum alphafetoprotein, lactate, lactate dehydrogenase, blood ammonia,
G. arterial blood gas, and urine for reducing substances.
 DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE
II. Specific work-up
A. Infectious
• IgM anti- hepatitis A virus, IgM anti - hepatitis E virus,
hepatitis B virus surface antigen, IgM anti-hepatitis B core
antibody, cytomegalovirus PCR, IgM varicella zoster virus, IgM
Epsteinbarr virus, HIV 1 and 2
 DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE
II. Specific work-up
B. Wilson disease
• Serum ceruloplasmin
• 24 hour urinary copper estimation,
• KF ring.
• Clue to etiology:
– alkaline phosphatase / bilirubin ratio <4.0
– AST/ ALT ratio > 2.2
– ± evidence of Coombs negative hemolysis
 DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE
II. Specific work-up
C. Autoimmune
• Coombs test,
• antinuclear antibody (> 1:40),
• liver kidney microsomal antibody,
• smooth muscle antibody (>1:20),
• Immunoglobulin G levels
 DIAGNOSTIC WORK UP FOR ACUTE LIVER FAILURE
II. Specific work-up
D. Hemophagocytosis
• Serum triglyceride
• Cholesterol
• ferritin
• bone marrow biopsy

E. Drug overdose
• Acetaminophen drug levels
• valproate drug levels
Age-specific diagnostic priorities for children with acute liver failure
<3 months of age
Herpes blood PCR (or other testing: HSV
IgM, viral culture of blood or CSF, CSF PCR)
Enterovirus blood PCR (or other testing)
Lactate, pyruvate (mitochondrial screen)
Plasma acylcarnitine profile (fatty acid
oxidation defects)
Ferritin (screen for gestational alloimmune
liver disease [neonatal hemachromatosis])
Serum amino acid profile (urea cycle and
metabolic)
Echocardiogram: Cardiac dysfunction
Abdominal ultrasound with Doppler
(vascular and anatomic)
Confirm newborn screening results
(galactosemia and tyrosinemia)
Confirm maternal hepatitis B serology
3 months to 4 years
HBsAg, HAV IgM, EBV VCA IgM or EBV PCR
Lactate, pyruvate (mitochondrial screen)
Autoimmune markers: ANA, ASMA, ALKM, IgG
Drug history, acetaminophen level
Plasma acylcarnitine profile (fatty acid oxidation defects)
Serum amino acids
Abdominal ultrasound with Doppler (vascular and
anatomic)
5 years to 18 years
HBsAg, HAV IgM, EBV (EBV VCA IgM or PCR)
Autoimmune markers: ANA, ASMA, ALKM, IgG
Ceruloplasmin
Drug history, acetaminophen level
Lactate, pyruvate (screen for mitochondrial disorders)
Plasma acylcarnitine profile (Fatty acid oxidation defects)
Serum amino acids
Abdominal ultrasound with Doppler (vascular and anatomic)
Additional diagnostic screening tests to consider, directed by history and clinical course
Infectious causes
Blood culture
Viral PCR in blood for adenovirus, enterovirus, EBV, HHV-6, parvovirus
Nasal wash for influenza (infections)
Hepatitis E antibody
Serologic tests for celiac disease (eg, tissue transglutaminase)
Soluble IL2R, ferritin in older patients, triglycerides (hemophagocytic lymphohistiocytosis)
Echocardiogram (cardiac)
MRI for tissue iron (gestational alloimmune liver disease [neonatal hemochromatosis])
Urine succinyl acetone (tyrosinemia)
Urine orotic acid (urea cycle defects)
Urine organic acids (metabolic)
Liver copper, Wilson gene mutation analysis (Wilson)
Liver biopsy for histology, culture, electron microscopy
 MANAGEMENT
1. Evaluate the cause of pediatric acute liver failure (PALF),
guided by the patient’s age and prioritizing the diagnosis of
treatable disorders

2. Monitor the function of each organ system

3. Identify and treat complications

4. Provide medical support to maximize health and survival

 Complications of acute liver failure
5. Infections
1. Metabolic
I. Sepsis
I. Hypoglycemia
II. Spontaneous bacterial peritonitis
II. Hypophosphatemia
III. Hypokalemia 6. Ascites
IV. Hyponatremia 7. Neurologic
2. Acid–Base Disturbance I. Encephalopathy
I. Respiratory alkalosis II. Cerebral edema
II. Metabolic acidosis III. Seizures
3. Gastrointestinal IV. Intracranial hemorrhage
I. Bleeding—ulcers, gastritis 8. Multiorgan Dysfunction
II. Pancreatitis I. Pancreatitis
4. Hematologic II. Pulmonary edema/hemorrhage
I. Aplastic anemia III. Shock
II. Coagulopathy IV. Acute tubular necrosis
III. Disseminated intravascular coagulopathy V. Hepatorenal syndrome
VI. Respiratory failure
 MANAGEMENT
 Care setting
– should be cared for in a pediatric intensive care unit

– close serial observation with surveillance for potential life-threatening

complications.

– Enteric isolation procedures must be enforced

– blood specimens should be labeled as potentially infectious.

– All medical personnel should consider wearing protective gowns, gloves, and
masks when dealing with a child in acute liver failure.
 Management of Fulminant Hepatic Failure
A. No sedation except for procedures

B. Minimal handling

C. Enteric precautions until infection ruled out

D. Monitor

E. Fluid balance

F. Maintain circulating volume with colloid/FFP

G. Coagulation support only if required

H. Drugs

I. Nutrition
Management of Fulminant Hepatic Failure
• Drugs:
A. Vitamin K
B. H2 antagonist
C. Antacids
D. Lactulose
E. N-acetylcysteine for acetaminophen toxicity
F. Broad-spectrum antibiotics
G. Antifungals
Management of Fulminant Hepatic Failure
• Monitor:
A. Heart and respiratory rate
B. Arterial BP, CVP
C. Core/toe temperature
D. Neurological observations
E. Gastric pH (>4)
F. Blood glucose (>4 mmol/L)
G. Acid-base
H. Electrolytes
I. PT, PTT
 MANAGEMENT
A. every 4 hours
– vital signs, including
I. blood pressure every 4 hours, more frequently in an unstable child
II. continuous oxygen saturation monitoring
B. every 12 hourly
A. neurological observations/coma grading,
B. Electrolyte,arterial blood gases, blood sugar every 12 hourly (more frequently in an unstable child);
C. prothrombin time should be monitored 12 hourly till patient stabilizes or decision to perform a transplant is
taken
C. daily
A. daily measurements of liver span and prescription review
B. liver function tests, blood urea, serum creatinine, calcium and phosphate at least twice weekly.
D. Surveillance of blood and urine cultures should be done during the course of illness.
 MANAGEMENT
• Coma grade
– It should be monitored to detect any progression.
• Avoid
1. sedatives,
2. antiemetics,
3. hepatotoxic drugs, and
4. corticosteroids.
 MANAGEMENT
• No therapy is known to reverse hepatocyte injury
or to promote hepatic regeneration
 MANAGEMENT
identified and corrected. precipitate encephalopathy
A. Gastrointestinal hemorrhage,
B. infection,
C. constipation,
D. sedatives,
E. electrolyte imbalance, and
F. hypovolemia
 MANAGEMENT
• Intensive care unit
– Progression beyond stage I indicates transfer to an
intensive care unit

– Placement of arterial and central venous and urinary

catheters.

– Continuous pulse, blood pressure, and ECG monitoring.

 MANAGEMENT
• Intensive care unit
– Endotracheal intubation may be required to
I. prevent aspiration,
II. to reduce cerebral edema by hyperventilation, and to
III. facilitate pulmonary toilet.
– Mechanical ventilation and supplemental oxygen are often
necessary in advanced coma.
 MANAGEMENT
• CARDIOPULMONARY
– Excessive fluid administration contributes to pulmonary edema and should be avoided.
– For patients who develop pulmonary edema,
• careful fluid restriction and discrete use of diuretics may be needed in some instances,
but should be used with caution because these interventions can reduce organ
perfusion and precipitate renal failure.

– Central venous pressure monitoring may assist in assessing volume needs for the child
– Ionotropic support may be needed to maintain perfusion of vital organs.
Management of Fulminant Hepatic Failure
• Fluid balance:
A. 85% maintenance
B. Dextrose 10%-50% (provide 6-10 mg/kg/min)
C. Sodium (0.5-1 mmol/L)
D. Potassium (2-4 mmol/L
 MANAGEMENT
• Fluids : However, as a general rule,
• restricted for most patients with PALF.
• Total daily fluid intake (including medications and blood products)
should initially be restricted to between 85 to 95 percent of the
maintenance fluid requirement.
 MANAGEMENT
• Fluids
– At the same time, the serum glucose should be
maintained between 90 and 110 mg/dL.

– Adjustment in fluid rates is based upon the clinical

conditions
Management of Fulminant Hepatic Failure
• Nutrition:
A. Initial protein intake should not exceed 1 g/kg/day
B. Nutrition support should be maintained to avoid a catabolic
state.

C. PN if ventilated
 MANAGEMENT
• NUTRITION
– We suggest the following parameters for PN in patients with
pediatric acute liver failure (PALF):

A. Total fluid input including PN, blood products, and

medications should generally be limited to between 85 to 95
percent of the maintenance fluid requirement to avoid
excessive hydration
 MANAGEMENT
• NUTRITION
– We suggest the following parameters for PN in patients with
pediatric acute liver failure (PALF):

B. Protein input should generally be no more than 1 g/kg/day, but

this may need to be reduced to 0.5 mg/kg/day for patients with
elevated serum ammonia levels
 MANAGEMENT
• NUTRITION
– We suggest the following parameters for PN in patients with pediatric
acute liver failure (PALF):

C. Trace metals (trace elements)

• should generally be eliminated or reduced.

• This is because copper and manganese are metabolized in the liver.

• Moreover, chromium, molybdenum, and selenium should be eliminated or

reduced if renal disease is also present.
 MANAGEMENT
• METABOLIC
– Metabolic abnormalities often seen in patients with acute liver failure (ALF)
include :

A. Hypoglycemia –

• caused by impaired hepatic gluconeogenesis and depleted glycogen stores.

• treated with continuous infusion of glucose

• Glucose infusion rates of 10 to 15 mg/kg/minute may be

required to achieve stable serum glucose levels.
 MANAGEMENT

• METABOLIC
B. Hypokalemia – caused by
1. dilution from volume overload
2. ascites, or
3. renal wasting.
 MANAGEMENT
• METABOLIC
C. Hypophosphatemia –
• Serum phosphorus should be monitored frequently, as hypophosphatemia can be
profound.

• the mechanism is unknown,

• hypophosphatemia is presumed to result from increased needs due to active liver cell
regeneration.

• Hyperphosphatemia, often associated with renal insufficiency, is considered a poor

prognostic sign
 MANAGEMENT
• Acid-base balance
A. Respiratory alkalosis
• due to hyperventilation

• requires no action.

B. Respiratory acidosis
• due to cerebral or respiratory infection

• requires tracheal intubation , paralysis, and mechanical ventilation.

C. Metabolic acidosis
• requires correction with sodium bicarbonate.
 MANAGEMENT
• METABOLIC
D. Acid-base disturbances –
 metabolic acidosis from
1. hepatic necrosis

2. Shock

3. increased anaerobic metabolism

4. inborn errors of metabolism.

 MANAGEMENT
• HEMATOLOGIC ; Coagulopathy
– The prothrombin time (PT) and international normalization ratio (INR) are

used to assess the severity of liver injury in the setting of acute liver failure

(ALF)

• because these tests reflect hepatic production of clotting factors,

particularly factors V and VII, which have the shortest half-lives.

 MANAGEMENT
• HEMATOLOGIC ; Coagulopathy
• This is because ALF reduces both procoagulant proteins (eg, factor V, VII, X, and

fibrinogen) and anticoagulant proteins.

• A single dose of vitamin K should be administered once to initially assess

response of the coagulation profile.

• However, daily administration of vitamin K is unnecessary

 MANAGEMENT
• HEMATOLOGIC ; Coagulopathy
– Efforts to “correct” the PT/INR with plasma or other procoagulation products such as

recombinant Factor VII should be avoided.

– Correction of the PT/INR should be limited to patients with active bleeding or in

anticipation of an invasive surgical procedure.

 MANAGEMENT
• Bleeding tendency
– Coagulopathy can be treated by
A. fresh frozen plasma and
B. parenteral vitamin K administration.
C. Recombinant factor Vlla has been used for transient
correction of coagulopathy refractory to other measures.
 MANAGEMENT
• Bleeding tendency
– Prophylactic use of
A. antacids, or
B. H2 receptor blockers, or
C. both
• should be considered because of high risk of GIT bleeding.
 MANAGEMENT
• HEMATOLOGIC : Aplastic anemia
– Bone marrow failure,

– characterized by a spectrum of features ranging from mild pancytopenia to aplastic anemia

– occurs in a significant minority of children with ALF

– Treatment includes

– immunomodulatory medications that include steroids, cyclosporine A, and antilymphocyte

or antithymocyte globulin, as well as hematopoietic stem cell transplant.
 MANAGEMENT
• Renal failure
– Causes include
A. Dehydration
B. acute tubular necrosis

C. functional renal failure (hepatorenal syndrome)

→→→ prerenal or renal uremia..
 MANAGEMENT
• Renal failure
– renal doses” of dopamine may help to maintain
renal perfusion.

– Renal replacement therapy with hemofiltration or

dialysis may be necessary in some cases, but only
liver transplantation (LT) can reverse HRS
 MANAGEMENT
Infection
– The patients have increased susceptibility of bacterial and fungal infection
– possibly due to low serum complement and defective opsonization.
– Septicemia, peritonitis, pneumonia, and UTI may occur.
– The child should be nursed in protective isolation.
– White blood cell count, blood cultures (aerobic, anaerobic, and fungal), urine
culture, and chest Xray should be done.
– Broad-spectrum antibiotics (not hepatotoxic) can be started if
• Fever, ascites, or clinical deterioration until the results of cultures are available.
 INFECTION
Infection
– Sepsis is the most frequent severe infection, with the most
frequently implicated organisms being gram-positive
(Staphylococcus aureus, S epidermidis, and streptococcus)
organisms, presumably of skin origin.
– Occasionally gram-negative bacteria or fungal infections
are observed.
 MANAGEMENT
• GASTROINTESTINAL ; Ascites
– Ascites develops in some but not all patients with acute
liver failure (ALF).
– Precipitating factors include
A. hypoalbuminemia,
B. excessive fluid administration, and
C. infection.
 MANAGEMENT
• GASTROINTESTINAL ; Ascites
– The primary treatment is
A. moderate fluid restriction.
B. Diuretics should be reserved for patients with
1. respiratory compromise or
2. generalized fluid overload.

C. Overly aggressive diuresis may precipitate hepatorenal syndrome.

 MANAGEMENT
• GASTROINTESTINAL ; Bleeding
– Gastrointestinal bleeding is surprisingly infrequent,
given the degree of coagulopathy.

– This is probably because of a balanced reduction in the

procoagulant and anticoagulant proteins
 MANAGEMENT
• GASTROINTESTINAL ; Bleeding
– Prophylactic use of acid-reducing agents is often initiated when
the patient is admitted, but their usefulness is difficult to assess.
– Causes for bleeding include
1. gastric erosions or ulcers due to nonsteroidal anti-inflammatory drugs
(NSAIDs), or
2. idiopathic gastroduodenal ulceration.
 MANAGEMENT
• GASTROINTESTINAL ;Bleeding
– Infection can precipitate bleeding in this vulnerable
population, so blood cultures and initiation of antibiotics
should also be considered when bleeding develops.
– Administration of platelets, blood, and plasma is necessary
if bleeding is hemodynamically significant.
 MANAGEMENT
• GASTROINTESTINAL ;Pancreatitis
– Biochemical and clinical pancreatitis is increasingly
recognized as a condition associated with multisystem
failure in critically ill children.
– patients who develop pancreatitis in the setting of acute
liver failure, glucose and fluid management may become
even more challenging.
 MANAGEMENT
• Encephalopathy
– determined by serial clinical evaluations of
1. Behavior
2. Cognition
3. neurological examination, and,
4. occasionally, electroencephalogram (EEG)
– While neurologic morbidity remains a major determinant of
outcome following pediatric ALF
 MANAGEMENT
• Encephalopathy
– Hepatic encephalopathy is not always clinically apparent in infants and
young children.
– other causes of an altered mental status such as
1. Sepsis
2. Hypotension
3. electrolyte disturbances
4. Hypoglycemia
5. anxiety, or “intensive care unit (ICU) psychosis” is difficult for all age groups.
 Precipitate Encephalopathy
1. Gastrointestinal hemorrhage,
2. infection,
3. constipation,
4. sedatives,
5. electrolyte imbalance,
6. hypoglycemia, and
7. hypovolemia
MANAGEMENT OF ENCEPHALOPATHY
• Flumazenil, a benzodiazepine antagonist, may
reverse early hepatic encephalopathy.

• Morphine or other opiates used in small doses

can relieve pain associated with monitoring and
catheter placement
 MANAGEMENT
• Enteric production of ammonia and nitrogenous toxins can be
managed by
1. The gut should be purged with several enemas.
2. Protein intake should be restricted or eliminated.
3. GIT hemorrhage should be prevented or rapidly stopped.
4. Lactulose: It can be given orally or by nasogastric tube (10-50 mL
every 2-4 hr) sufficient to cause diarrhea or given as retention
enema (diluted 1:3) every 6 hr.
 MANAGEMENT
• Bowel “decontamination” with

1. rifaximin or
2. neomycin
3. metronidazole
 MANAGEMENT
• Cerebral edema
– Cerebral edema is a life threatening complication of ALF
– It may lead to
1. ischemic and hypoxic brain injury, or
2. brainstem herniation and
3. death

– commonly in those with advanced hepatic encephalopathy (stage III

or IV) and can progress rapidly
 MANAGEMENT
• Cerebral edema
– Monitoring of intracranial pressure by observing the progression or the
regression of the mental changes (clinical) and by subdural transducer.

– Corticosteroid therapy has shown a worsened outcome in controlled trials.

 MANAGEMENT
• Cerebral edema

A. Oxygen saturation above 95 percent

B. Head elevation of 20° to 30°
C. Total daily fluid between 85 and 90 percent of maintenance
D. Diastolic pressure >40 mmHg
E. initial restriction of protein intake to no more than 1 g/kg/day,
F. minimizing excess stimulation,
G. treating suspected sepsis, and, if possible,
 MANAGEMENT
• ENCEPHALOPATHY
– For patients with progressive HE, we suggest medical therapy with
A. lactulose ,
B. Bowel “decontamination” with
A. rifaximin or
B. neomycin
– can be used as a second-tier treatment, but ototoxicity and nephrotoxicity
are potential risks when neomycin is used
C. metronidazole
 MANAGEMENT
• Cerebral edema include
A. hypertonic saline to maintain serum sodium between 145
and 150 mEq/L, and
B. mannitol keeping serum osmolarity less than 320 mOsm/L
to create a more favorable osmotic gradient to extract
water from the brain.
C. Hypothermia has been used in adults with acute liver
failure with some success, but has not been studied in
children
 MANAGEMENT
• seizures
– Children with ALF may experience generalized or focal seizures, or
nonconvulsive (electrographic) seizures (NCS).
– treatment begins with
• phenytoin

– refractory to phenytoin, therapeutic options may include

1. midazolam infusion,
2. phenobarbital ,
3. levetiracetam , or
4. topiramate .
TREATMENT OPTIONS FOR ACUTE LIVER FAILURE

• intravenous NAC
– as treatment in children with acute liver failure not resulting from
acetaminophen toxicity will hopefully

– bridge to transplantation, experimental treatment strategies have

included growth hormone, plasmapheresis, antioxidants, and other
cytoprotective agents, along with temporary “bioartificial” liver support.
 MANAGEMENT
• Liver dialysis with

– an albumin-containing dialysate and biologic liver

support Devices involving perfusion of the patient's
blood through a cartridge containing liver cell

– lines or porcine hepatocytes can remove some toxins,

improve serum biochemical abnormalities, and in
some cases, improve neurologic function.
 MANAGEMENT
• Liver transplantation
– may offer the best possibility of survival, but it is usually precluded by donor availability.
– Reduced-size allograft and living donor transplantation are important advances.
– Partial auxiliary orthotopic or heterotopic liver transplantation is successful in some cases
that allowed regeneration of the native liver and eventual withdrawal of
immunosuppression.
– Liver transplantation should not be done in patients with liver failure (progressive
neurologic deterioration continues post transplant)
 Fulminant hepatic failure: etiology and indications
for liver transplantation
Acetaminophen-induced disease
• Arterial pH <7.3 (independent of the grade of encephalopathy)
OR
• Grade III or IV encephalopathy and
• Prothrombin time >100 s and
• Serum creatinine >3.4 mg/dL (301 μmol/l)
All other causes of fulminant hepatic failure
Prothrombin time >100 s (independent of the grade of encephalopathy)
OR
Any three of the following variables (independent of the grade of encephalopathy)
1. Age <10 years or >40 years
2. Etiology: non-A, non-B hepatitis, halothane hepatitis, idiosyncratic drug reactions
3. Duration of jaundice before onset of encephalopathy >7 days
4. Prothrombin time >50 s
5. Serum bilirubin >18 mg/dl (308 μmol/l)
 MANAGEMENT
• Immunosuppressive therapy
– It may be effective in fulminant autoimmune hepatitis
 MANAGEMENT
• The antiviral drug pleconaril:
– It is the treatment of choice for fulminant enteroviral
hepatitis in the neonate.
ACETAMINOPHEN
POISONING
 INITIAL STABILIZATION/THERAPY
• Maintain vital signs within normal limits;
• IV fluid administration is usually indicated
• Assess the serum acetaminophen concentration at
least 4 hr post-ingestion
 INITIAL STABILIZATION/THERAPY
First Line
– IV NAC is indicated in a single acute ingestion of acetaminophen
when the acetaminophen concentration ≥4 hr post-ingestion is
above the treatment line
– It is ideal to start NAC within 8 hr of ingestion in order to prevent
significant hepatoxicity and mortality

Second Line
– Consider activated charcoal
 INITIAL STABILIZATION/THERAPY
A. NAC IV dosing (21-hr NAC protocol):
– 150 mg/kg over 60 min, then 50 mg/kg over 4 hr, then 100
mg/kg over 16 hr
– It is usually mixed with 5% dextrose
B. NAC oral dosing:
– 140 mg/kg PO loading dose followed by 70 mg/kg PO q4h
for 72 hr.
 Efficacy of treatments of hepatic encephalopathy
Ammonia hypothesis
A. Decrease in ammoniagenic substrates
1. Enemas with lactulose
2. Restriction of dietary protein intake
B. Inhibition of ammonia production
1. Antibiotics
1. Neomycin
2. Rifaximin
3. Metronidazole
4. Vancomycin
2. Disaccharides
1. Lactulose
2. Lactitol
3. Lactose in lactase deficiency
3. Modification of colonic flora
Lactobacillus SF 68
 Efficacy of treatments of hepatic encephalopathy
Fluids
A. 85% maintenance
B. Dextrose 10%-50% (provide 6-10 mg/kg/min)
C. Sodium (0.5-1 mmol/L)
D. Potassium (2-4 mmol/L
Infection
Renal failure
GASTROINTESTINAL
Cerebral edema
Liver dialysis with
Metabolic ammonia removal
Ornithine-aspartate
Benzoate
Metabolic ammonia removal
Ornithine-aspartate
Benzoate
False neurotransmitter hypothesis
Branched chain amino acid supplementation
Modified amino acid solutions (FO80 type)
"COMA" solutions
Dietary BCAA supplementation
Increased dopamine
L-DOPA, bromocriptine
GABA hypothesis
Flumazenil
Other
Zinc
 PROGNOSIS
• The mortality rate may reach 80-90% in the
absence of liver transplantation
 PROGNOSIS
• Children with hepatic failure might fare somewhat
better than adults, but overall mortality with
supportive care alone exceeds 70%.

• The prognosis varies considerably with the cause of

liver failure and stage of hepatic encephalopathy.
 PROGNOSIS
• According to the etiology:
A. Survival rate of 50 -60% occurs in cases of FHF due to HAV or HBV infection
and acetaminophen overdose

B. but it is only 10-20% of cases due to idiopathic form of FHF or an acute onset
of Wilson disease.
 PROGNOSIS
• In patients who progress to stage IV coma ,the prognosis is extremely poor.
• Brainstem herniation is the most common cause of death.
• Major complications such as sepsis, severe hemorrhage, or renal failure increase
the mortality.
• The prognosis is particularly poor in patients with liver necrosis and multiorgan
failure.
• Age <1 yr, stage 4 encephalopathy, an INR >4, and the need for dialysis before
transplantation have been associated with increased mortality.
 PROGNOSIS
• The overall mortality exceeds 70%.

• Death is usually attributable to

1. cerebral edema with or without herniation,

2. massive hemorrhage of the upper intestinal tract from stress injury,
3. sepsis
4. multisystem organ failure.

• The mortality rate is highest in patients <1 yr of age.

 PROGNOSIS
• Causes of death:

A. neurological (67%)
B. GIT hemorrhage (13%)
C. bacterial infection (13%)
D. hemodynamic complication (hypovolemia, arrhythmia)
E. progressive respiratory and renal failure (other patients).
 PROGNOSIS
• According to the stage of hepatic encephalopathy:

– Extremely poor prognosis in cases with stage IV coma.

• According to laboratory data:

– Poor prognosis with a prothrombin time more than 50 sec

– serum bilirubin more than 17.5 mg%.

– Pretransplantation serum bilirubin concentration or the height of hepatic enzymes is not predictive of
posttransplantation survival.

– plasma ammonia concentration >200 µmol/L is associated with a

5-fold increased risk of death.
 PROGNOSIS
• According to presence or absence of complications:

– Poor prognosis with

A. severe hemorrhage

B. Sepsis

C. renal failure

D. aplastic anemia (a fatal complication of idiopathic form of FHF).

• Liver transplantation:

– It will lead to -75% survival rate in the 6 mo post liver transplantation.

 Admission Criteria of hepatitis
• fulminant hepatitis indicated by
1. Biochemical evidence
2. coagulopathy evidence
• encephalopathy require hospital admission.
• Persistent vomiting, dehydration, and electrolyte abnormalities
• High fever 39.5c
• Comorbidity