Acute self-limiting metabolic insult leading to a rapidly progressive encephalopathy with hepatic dysfunction.
- 1956: Najib Khan first described the fever in Jamshedpur, hence the disease is also called ‘Jamshedpur Fever’
- 1964: Reye & colleagues described the disease in Australia
Etiology
- Drugs: Salicylates (eg .Aspirin) (M/C cause)
- Toxins: Aflatoxins
- Viral infections: Influenza B, chickenpox, varicella
- Inborn errors of metabolism: Single enzyme defects of β-oxidation
Pathophysiology
Biochemical pathway:
Generalised mitochondrial dysfunction due to the inhibition of fatty acid β-oxidation
Damage to hepatocyte mitochondria
↓
Liver dysfunction
↓
↑ N2-containing toxins
↓
↑ NH3 in blood
↓
Cross BBB
↓
Target astrocytes
(swelling + oxidative damage)
↓
Encephalopathy
(swelling, inflammation, oedema)
Histopathology:
- Marked microvesicular steatosis
Presentation
- Persistent vomiting
- Anorexia
- Personality changes
- Irregular breathing
- Confusion
- Drowsiness
- Seizures
- Loss of consciousness
- Decerebration
- Coma
- Hepatomegaly
- No jaundice
Diagnosis
Diagnostic criteria:
Blood panel:
- ↑ blood NH3
- ↓ blood sugar
- ↑ prothrombin time
- LFT
Differential diagnosis:
| Reye’s Syndrome | Hepatic Encephalopathy of Fulminant Hepatitis | |
| CLINICAL PRESENTATION | ||
| Onset | Sudden | Gradual |
| Prodrome | URTI or chicken pox infection, biphasic course | Fever, anorexia, jaundice |
| Community Epidemiology | Respiratory disease or chickenpox | Frequently hepatitis or rural water supply or suburban septic tanks |
| Jaundice | No | Yes |
| Liver size | Normal or considerably enlarged | Maybe palpable |
| Fetor hepaticus | Absent | Present |
| Neurologic | Combative
Intermittently agitated Screaming Marked decerebrate posturing No flap | Somnolent
Sometimes delirious Liver flap may be present |
| Signs of increased intracranial pressure | Present early | Absent early; may develop |
| Course | Encephalopathy runs course in 3-7 days | Encephalopathy persists for days to weeks |
| Liver biopsy | Yellow or white; very fatty | Green; not fatty |
| BIOCHEMICAL ABNORMALITIES | ||
| Bilirubin | < 3.5 | > 5 |
| Blood sugar | Maybe hypoglycemic; readily corrected | Maybe hypoglycaemic; hypoglycaemia may be profound and difficult to correct |
| SGOT/SGPT | Elevated, variable | Elevated, variable |
| NH3 | Elevated before treatment; normalises rapidly with treatment | Levels unpredictable |
| Blood-clotting studies | Prothrombin time prolonged; easily correctable | Prothrombin time prolonged; difficult to correct |
| Disseminated intravascular coagulopathy (thrombocytopenia) | Absent | Maybe present |
Management
- Manage swelling + oedema: Mannitol + glycerol
- Insulin: Increase glucose metabolism
- Corticosteroids: Reduce cerebral edema
- Diuretics: Reduce fluid and ICP
- Vitamin K, plasma, platelets: Reduce bleeding
- Cooling measures: Maintain body temperature