Fulminant Hepatic Failure (FHF) (Acute Liver Failure (ALF) ) : DR / Reyad Alfaky
Fulminant Hepatic Failure (FHF) (Acute Liver Failure (ALF) ) : DR / Reyad Alfaky
Fulminant Hepatic Failure (FHF) (Acute Liver Failure (ALF) ) : DR / Reyad Alfaky
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
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
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;
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
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.
E. Drug overdose
• Acetaminophen drug levels
• valproate drug levels
Age-specific diagnostic priorities for children with acute liver failure
<3 months of age 3 months to 4 years
Herpes blood PCR (or other testing: HSV HBsAg, HAV IgM, EBV VCA IgM or EBV PCR
IgM, viral culture of blood or CSF, CSF PCR) Lactate, pyruvate (mitochondrial screen)
Enterovirus blood PCR (or other testing) Autoimmune markers: ANA, ASMA, ALKM, IgG
Drug history, acetaminophen level
Lactate, pyruvate (mitochondrial screen)
Plasma acylcarnitine profile (fatty acid oxidation defects)
Plasma acylcarnitine profile (fatty acid Serum amino acids
oxidation defects)
Abdominal ultrasound with Doppler (vascular and
Ferritin (screen for gestational alloimmune anatomic)
liver disease [neonatal hemachromatosis])
Serum amino acid profile (urea cycle and 5 years to 18 years
metabolic) HBsAg, HAV IgM, EBV (EBV VCA IgM or PCR)
Echocardiogram: Cardiac dysfunction Autoimmune markers: ANA, ASMA, ALKM, IgG
Abdominal ultrasound with Doppler Ceruloplasmin
Drug history, acetaminophen level
(vascular and anatomic)
Lactate, pyruvate (screen for mitochondrial disorders)
Confirm newborn screening results Plasma acylcarnitine profile (Fatty acid oxidation defects)
(galactosemia and tyrosinemia) Serum amino acids
Confirm maternal hepatitis B serology 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
– 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
D. Monitor
E. Fluid balance
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
– 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.
C. PN if ventilated
MANAGEMENT
• NUTRITION
– We suggest the following parameters for PN in patients with
pediatric acute liver failure (PALF):
A. Hypoglycemia –
• 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.
• hypophosphatemia is presumed to result from increased needs due to active liver cell
regeneration.
• requires no action.
B. Respiratory acidosis
• due to cerebral or respiratory infection
C. Metabolic acidosis
• requires correction with sodium bicarbonate.
MANAGEMENT
• METABOLIC
D. Acid-base disturbances –
metabolic acidosis from
1. hepatic necrosis
2. Shock
used to assess the severity of liver injury in the setting of acute liver failure
(ALF)
– Treatment includes
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
• intravenous NAC
– as treatment in children with acute liver failure not resulting from
acetaminophen toxicity will hopefully
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%.
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%.
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:
– Pretransplantation serum bilirubin concentration or the height of hepatic enzymes is not predictive of
posttransplantation survival.
A. severe hemorrhage
B. Sepsis
C. renal failure