‫بسم هللا الرحمن الرحيم‬

Case presentation

 A 3 years old, male child, presented by fever, abdominal

pain, and vomiting.
 Two days later, jaundice appeared with dark colored
urine and light colored stools.
 Parents sought medical advice and their child was
diagnosed as an acute hepatitis (T.Bil: 8 mg/dl; ALT:
1230 IU/l) and received supportive treatment.
 Two weeks later, after an initial improvement, the child
developed deepening of jaundice.
 Case presentation

• Investigations at this time revealed:

- T.Bil: 19 mg/dl
- D.Bil: 16 mg/dl
- AST: 2403
- ALT: 2870
- PT: 31 sec
- Anti-HAV-IgM: positive
• The child received parenteral vitamin K together
with continuation of supportive therapy.
 Case presentation

• One week later, there was more deepening of

jaundice with disturbed conscious level.
• Investigations revealed:
- T.Bil: 24 mg/dl
- D.Bil: 14 mg/dl A classic scenario
- AST: 780 of FHF
- ALT: 978
- PT: 47 sec
• The condition deteriorated to death
Fulminant hepatic failure
(FHF)

By

Ahmad Sira, MD
Lecturer of pediatric hepatology
National Liver Institute- Menofiya University
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Definition

The broadest definition The narrow definition

of ALF of ALF

 Loss of liver function  Loss of liver function

 Within weeks or a few  Within 8 weeks of the onset
months of the onset of of liver disease
liver disease

In the absence of preexisting liver disease

 Definition

PALF Study Group definition of ALF:

– The acute onset of liver disease with no known
evidence of chronic liver disease
+
– Biochemical and/or clinical evidence of severe liver
dysfunction:
• Hepatic-based coagulopathy, with PT ≥ 20 s or INR ≥ 2.0, that
is not corrected by parenteral vitamin K
and/or
• Hepatic encephalopathy (must be present if the PT is 15.0–
19.9 s or INR 1.5–1.9, but not if PT ≥ 20 s or INR ≥ 2.0)
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Etiology

& Neonates & Infants > 6 mo

infants up to 6 mo older children
Herpes viruses
Sepsis
1- Infections 1- Infections
Galactosemia
2- Metabolic Tyrosenemia 2- Drugs
CHD
3- Ischemia Myocarditis 3- Toxins
4- Miscellaneous 4- Metabolic
5- Autoimmune
6- Ischemia
7- Miscellaneous
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Pathology Biochemistry

ALT & AST Bilirubin

1- Hepatic necrosis
- Viral infection
- Idiosyncratic drug reaction
1,000-80,000 IU/L 10-60 mg/dl

2- Hepatocellular degeneration
- Metabolic
- Toxic
<400 IU/L <12 mg/dl

3- Underlying cirrhosis
- Tyrosinemia type-I
- Wilson’s disease
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Pathogenesis

 Exposure of a susceptible individual

 Hepatocyte injury
 Potentiation
 Regeneration
 Termination
– Terminal hepatic failure
– Spontaneous recovery
– Chronicity
Pathogenesis of encephalopathy

Liver failure

Production of
Elimination of
Neuroregulatory
neurotoxins
substances

Brain dysfunction
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Clinical manifestations

 No past history of liver disease

 Acute hepatic dysfunction
- Clinical
- Laboratory

 Warning signs of hepatic failure

– Prolonged PT, unresponsive to vitamin K (particularly at presentation).
– Persistent jaundice, with a rapid increase in bilirubin in association with a
progressive decline in serum aminotransferase levels.
– Decreasing liver size.
– Increasing lethargy or occasionally hallucinations.
– Rarely, hemorrhagic diathesis and systemic collapse.
 Clinical manifestations

Basic laboratory evaluation:

 Liver function tests:
- Bilirubin (total and direct)
- AST & ALT
- Albumin
 PT & PTT
 RBS
 ABG
 Electrolytes
 CBC
 Serum creatinine & urea
 Ammonia
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Diagnosis

Encephalopathy
Clinical features Deep jaundice or bad general condition
of liver failure Collapsing liver

Prolonged PT unresponsive to vitamin K

Biochemical features Increasing bilirubin with decreasing ALT
of liver failure Hyperammonemia

Selection of tests will be according to the

Specific suspicion of etiologies in different age
Diagnostic tests groups
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Differential diagnosis

Unrecognized chronic liver diseases

Reye syndrome
Reye-like syndrome
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Treatment

Hepatic Prevent Treat

support complications complications

Regeneration & recovery

Liver transplantation
 Treatment

Hepatic Prevent Treat

support complications complications
 Treatment

Treat
Standard care
complications
 Treatment

Treat
Standard care
complications
1- General measures
2- Fluid balance
3- Nutritional support
4- Antibiotic therapy
5- Other therapies
 Treatment

Treat
Standard care
complications
1- General measures 1- Hypoglycemia
2- Fluid balance 2- Hemorrhage
3- Nutritional support 3- Encephalopathy
4- Antibiotic therapy 4- Cerebral edema
5- Other therapies 5- Electrolyte and acid-base disturbances
6- Renal dysfunction
7- Ascites
8- Cardiovascular complications
9- Respiratory problems
10- Secondary bacterial and fungal infections
11- Pancreatitis
12- Aplastic anemia
Standard care 1- General measures

 ICU management
 Infectious precautions
 No sedation except for procedures
 Minimal handling
 Central line
 Arterial line
Standard care 1- General measures

 Nasogastric tube
 Urinary catheter
 Baseline investigations
 Monitoring:
– Vital signs (HR, RR, arterial BP and CVP, and Core/toe temperature)
– Neurological observations
– Blood glucose (> 70 mg/dl)
– ABG
– Creatinine, urea and electrolytes
– Bilirubin, aminotransferases, PT and PTT
– CBC
Standard care 2- Fluid balance

Hydration Volume overload

Renal function Cerebral edema

Volume of fluid: 75%

Maintenance fluids consist of:
Dextrose 10–50%
Sodium (0.5–1.0 mmol/kg/ day)
Potassium (2–6 mmol/kg/ day): guided by serum concentration
Phosphorus: IV phosphate may be given as potassium phosphate.
Maintain urinary output:
- Furosemide at 1–3 mg/kg every 6 h
- Colloid/fresh frozen plasma (FFP).
- If profound oliguria occur, consideration should be given to hemofiltration or dialysis.
Standard care 3- Nutritional support

 Maintain blood glucose > 70 mg/dl and ensure

sufficient carbohydrates for energy metabolism
 Reduce protein intake to 1–2 g/kg/day, either
enterally or parenterally
 Provide sufficient energy intake to reverse
catabolism, either enterally or parenterally
 Mechanically ventilated: parenteral nutrition
Standard care 4- Antibiotic therapy

Broad spectrum

?
or
Narrow spectrum
Standard care 5- Other therapies

 Vitamin K
 H2-antagonists:
- Ranitidine: 1-3mg/kg/8hrs
 Protone pump inhipitors:
- Omeprazole: 10-20mg/d
- Pantopprazole: 25mg/m2/d
 Antacids
 Sucralfate: 1-2 g/ 4hrs
 N-acetylcysteine
Treatment of complications 1- Hypoglycemia

 Level: < 40 mg/ dl

 Prevention:
-Frequent bedside monitoring (every 2-4h).
-Continuous IV glucose infusion (10-50%)
 Management:
-IV glucose 25%: 2ml/kg
 Refractory hypoglycemia: bad prognosis.
Treatment of complications 2- Coagulopathy &
Hemorrhage

 Causes:
- Deficient clotting factors: PT, PTT, FVII
- Thrombocytopenia
- DIC

 Sites of bleeding:
- GIT
- Pulmonary & ICH

 Treatment:
- FFP (10ml/kg/6hrs)
- Platelets transfusion (if < 50 ×109/L )
- Recombinant factor VII (NovoSeven; 80µg/kg)
Treatment of complications 3- Encephalopathy

 Definition:
- Any brain dysfunction that occurs as a result of acute hepatic
dysfunction
- Exacerbated by sepsis, GI bleeding, Electrolyte disturbances &
Sedation.
 Staging: 4 stages
 Treatment:
- Restriction of dietary protein
- Enteral antibiotics & Lactulose
- Controlling GI hemorrhage
- Correction of electrolyte and acid-base disturbances
Treatment of complications 4- Cerebral edema

 Pathophysiology:
- Iatrogenic: fluid overload, anaerobic metabolism, cerebral ischemia
- Non-iatrogenic: vascular integrity, astrocyte swelling
 Clinical manifestations & diagnosis:
- Changes in the neurological examination:
- Abnormally reacting or unequal pupils.
- Muscular rigidity and decerebrate posturing.
- Mild clonus and/or focal seizures.
- Vital signs:
- Alteration of respiratory pattern, bradycardia, hypertension.
- CT or MRI scans of the brain.
- A rise in ICP > 30 mmHg.
Treatment of complications 4- Cerebral edema

Treatment:
-Fluid restriction: < 75% of maintenance
-Mannitol: (0.5 g/kg every 4–6 h), serum osmolarity < 320 mosmol/L
-Hemofiltration, if diuretic therapy is ineffective or HRS
-Maintain cerebral perfusion pressure: by administering blood products,
albumin, and inotropic agents (epinephrine or norepinephrine).
-Convulsions should be treated promptly.
-Barbiturate coma (thiopentone: 0.5–1.0 mg/ kg i.v. followed by an infusion
of 0.5–3.0 mg/kg/h) may maintain cerebral perfusion.
Prognosis:
-The most frequent cause of death in ALF
-Contributes to reduced survival after LTx
Treatment of complications 5- Renal failure

Causes:
 Prerenal uremia
 Acute tubular necrosis (ATN)
 Hepatorenal syndrome: the commonest
Treatment:
 A fluid challenge (10 mL/kg)
 Hemodialysis or hemofiltration
 Liver transplantation
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Objectives

 Definition of FHF (acute liver failure)

 Etiology
 Pathology & biochemistry
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Differential diagnosis
 Treatment
 Prognosis
 Prognosis

 Survival rates:
- Fulminant hepatitis A
- Paracetamole overdose
- Hepatitis B
- Indeterminate hepatitis
- Halothane and other drug toxicities
- Absence of an obvious etiology

 Causes of death:
1. Brain edema
2. Hemorrhage
3. Renal failure
4. Sepsis
 Take- home message

 Consider acute hepatitis in a child presenting

with vomiting even without jaundice.
 In acute severe hepatitis ask for PT

 If PT is prolonged test the response to parent-

eral vitamin K
 Do not wait for encephalopathy to diagnose FHF
Thank
you