Hepatic Encephalopathy
Summary
Hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities occurring in patients with liver dysfunction, caused by accumulation of gut-derived neurotoxins (primarily ammonia) due to impaired hepatic clearance and portosystemic shunting. It ranges from subtle cognitive deficits (covert HE) to coma. Common precipitants include infection, GI bleeding, constipation, and electrolyte disturbance. Grade is assessed using the West Haven criteria. Treatment involves correcting precipitants, lactulose (to reduce ammonia absorption), and rifaximin (to reduce ammonia-producing bacteria). Prognosis depends on underlying liver disease severity.
Key Facts
- Definition: Neuropsychiatric syndrome in liver disease due to neurotoxin accumulation
- Prevalence: 30-45% of cirrhotics will develop overt HE
- Classification: Type A (acute liver failure), B (portosystemic bypass), C (cirrhosis)
- Pathognomonic: Asterixis (flapping tremor) + confusion in known liver disease
- Gold Standard Investigation: Clinical diagnosis + ammonia level (supportive)
- First-line Treatment: Lactulose + treat precipitant
- Prognosis: Development of HE indicates poor prognosis in cirrhosis
Clinical Pearls
Precipitant Pearl: ALWAYS look for a precipitant: infection (SBP), GI bleed, constipation, electrolytes, renal failure, sedatives.
Lactulose Pearl: Titrate lactulose to 2-3 soft stools/day. Works by trapping ammonia as NH4+ and reducing gut bacteria.
Ammonia Pearl: Ammonia level correlates poorly with severity but trend may be useful. Don't rely on it alone.
Rifaximin Pearl: Add rifaximin for secondary prevention if recurrent HE despite lactulose.
Mechanism
- Impaired hepatic clearance of gut-derived toxins (ammonia, mercaptans)
- Portosystemic shunting bypasses liver
- Ammonia crosses blood-brain barrier
- Astrocyte swelling, altered neurotransmission
- Neuroinflammation
Precipitants
| Precipitant | Mechanism |
|---|---|
| Infection (especially SBP) | Most common |
| GI bleeding | Protein load → ammonia |
| Constipation | Increased ammonia absorption |
| Electrolyte disturbance (hypoK, hypoNa) | Impaired NH3 to NH4+ |
| Renal failure | Reduced ammonia excretion |
| Sedatives (benzos, opioids) | CNS sensitivity |
| Dehydration | Renal impairment, concentrated toxins |
| TIPS | Increased shunting |
West Haven Criteria
| Grade | Features |
|---|---|
| Covert (minimal) | Subclinical, psychometric testing abnormal |
| Grade I | Mild confusion, shortened attention, altered sleep |
| Grade II | Lethargy, disorientation, inappropriate behaviour, asterixis |
| Grade III | Somnolent but rousable, marked confusion, bizarre behaviour |
| Grade IV | Coma, unresponsive |
Classic Signs
| Test | Purpose |
|---|---|
| Ammonia | Supportive (not diagnostic) |
| FBC | Infection |
| U&E | Electrolytes, renal function |
| LFTs | Liver synthetic function |
| Clotting | INR |
| Blood cultures | Sepsis |
| Urine/CXR | Infection source |
| Diagnostic paracentesis | SBP |
Algorithm
HEPATIC ENCEPHALOPATHY
↓
┌─────────────────────────────────────────────────────────┐
│ 1. IDENTIFY + TREAT PRECIPITANT │
│ - Septic screen + empirical antibiotics if infection │
│ - Stop sedatives │
│ - Correct electrolytes │
│ - Treat GI bleed │
│ - Treat constipation │
└─────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────┐
│ 2. LACTULOSE │
│ - 30-50mL TDS-QDS (titrate to 2-3 soft stools/day) │
│ - Enemas if unable to take orally │
└─────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────┐
│ 3. RIFAXIMIN (if recurrent) │
│ - 550mg BD for secondary prevention │
└─────────────────────────────────────────────────────────┘
↓
┌─────────────────────────────────────────────────────────┐
│ 4. SUPPORTIVE CARE │
│ - Nutrition (don't restrict protein) │
│ - Avoid sedatives │
│ - Prevent aspiration │
│ - ICU for Grade III-IV │
└─────────────────────────────────────────────────────────┘
- Development of overt HE is a poor prognostic marker
- 40% 1-year survival after first episode
- Consider transplant assessment
-
EASL Clinical Practice Guidelines for Hepatic Encephalopathy. J Hepatol. 2022.
-
Vilstrup H et al. Hepatic Encephalopathy in Chronic Liver Disease. Hepatology. 2014;60(2):715-735. PMID: 25042402
-
Bass NM et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071-1081. PMID: 20335583
Viva Points
"HE is neuropsychiatric dysfunction in liver disease due to ammonia. West Haven grades I-IV. Always seek precipitant: infection, GI bleed, constipation, electrolytes, sedatives. Treat with lactulose (2-3 stools/day), rifaximin for prevention. Don't restrict protein. Development of HE = poor prognosis."
Last Reviewed: 2026-01-01 | MedVellum Editorial Team