Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from severe hepatic dysfunction or portosystemic shunting in horses.
Overview and Clinical Importance
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from severe hepatic dysfunction or portosystemic shunting in horses. It represents a critical complication of liver failure and is characterized by abnormal mentation, behavioral changes, and motor dysfunction secondary to the accumulation of neurotoxins, primarily ammonia, that the failing liver cannot adequately metabolize.
HE is a high-yield topic for the NAVLE because it requires integration of hepatic physiology, neurology, toxicology, and clinical medicine. Understanding the pathophysiology, recognizing clinical signs, and implementing appropriate diagnostic and therapeutic strategies are essential competencies for equine practitioners.
High-YieldHepatic function must be reduced by 60-80% before clinical signs of liver failure, including HE, become apparent. This means horses may have significant subclinical liver disease before presenting with overt neurological signs.
| Mechanism |
Description and Effects |
| Ammonia Toxicity |
Ammonia crosses blood-brain barrier, causing astrocyte swelling (Alzheimer type II astrocytosis), glutamine accumulation, and cerebral edema |
| GABAergic Enhancement |
Increased endogenous benzodiazepine-like substances enhance inhibitory neurotransmission, causing CNS depression |
| False Neurotransmitters |
Aromatic amino acids accumulate and compete with catecholamine precursors, producing false neurotransmitters (octopamine, phenylethanolamine) |
| Manganese Deposition |
Impaired biliary excretion leads to manganese accumulation in basal ganglia, contributing to extrapyramidal signs |
| Energy Metabolism Failure |
Ammonia inhibits alpha-ketoglutarate dehydrogenase, impairing glucose oxidation and causing cerebral energy failure |
| Oxidative Stress |
Reactive oxygen species production and mitochondrial dysfunction contribute to neuronal injury |
Pathophysiology
The pathophysiology of HE is multifactorial, but hyperammonemia is considered the central mechanism. The liver normally converts ammonia, a byproduct of protein metabolism and bacterial urease activity in the GI tract, into urea via the urea cycle. When hepatic function fails or portal blood bypasses the liver through shunts, ammonia accumulates in systemic circulation.
Mechanisms of Neurotoxicity
NAVLE TipRemember that ammonia does NOT always correlate with severity of encephalopathy. While hyperammonemia is central to HE pathophysiology, blood ammonia levels may be normal in some horses with obvious neurological signs. Bile acids are often a more reliable marker of hepatic dysfunction.
| Etiology |
Key Features |
Clinical Pearls |
| Pyrrolizidine Alkaloid Toxicosis (Ragwort) |
Cause: Senecio spp., Crotalaria spp.
Pathology: Megalocytosis, periportal fibrosis, biliary hyperplasia
Course: Chronic, cumulative toxicity |
Dried plants in hay MORE palatable than fresh. Clinical signs appear weeks to months after exposure. Prognosis poor once clinical signs develop. |
| Theiler Disease (Serum Hepatitis) |
Cause: Equine pegivirus (TDAV) associated
Association: 4-10 weeks after equine-origin biologics
Course: Acute, fulminant hepatic failure |
History of tetanus antitoxin, plasma transfusion, or other equine biologics is key. Mortality 50-90% in symptomatic horses. Lactating mares post-partum at higher risk. |
| Cholangiohepatitis |
Cause: Bacterial infection of biliary tract
Signs: Fever, colic, icterus
GGT: Markedly elevated (greater than 15x normal) |
May be associated with cholelithiasis. Long-term antimicrobial therapy required. Better prognosis than other causes if treated early. |
| Hyperlipemia |
Predisposed: Ponies, donkeys, miniatures
Triggers: Stress, anorexia, late pregnancy, lactation
Lab: Elevated triglycerides, lipemic serum |
Massive hepatic lipidosis secondary to fat mobilization. Enteral nutrition support critical. Address underlying cause. |
| Tyzzer Disease |
Cause: Clostridium piliforme
Age: Foals less than 6 weeks
Course: Peracute, often sudden death |
Foal-specific disease. Often no premonitory signs. Consider in any young foal with sudden hepatic failure. |
| Portosystemic Shunt |
Type: Congenital vascular anomaly
Age: Young horses, foals
Feature: Stunted growth, episodic HE |
Rare in horses. HE may be triggered by high-protein meals. Liver enzymes may be normal or minimally elevated. |
Etiology of Equine Liver Disease Leading to HE
Multiple conditions can cause sufficient hepatic damage to precipitate HE. Understanding the common etiologies helps guide diagnostic workup and treatment.
Idiopathic (Primary) Hyperammonemia
An important differential diagnosis for HE is idiopathic or primary hyperammonemia, which occurs WITHOUT primary hepatic disease. This syndrome has been documented in adult horses with severe GI disease (enterocolitis, colic) and is thought to result from massive enteric ammonia production overwhelming the liver's detoxification capacity.
Key differentiating features: Normal liver enzymes (GGT, SDH), normal bile acids, marked hyperammonemia (greater than 150 micromol/L), severe metabolic acidosis, profound hyperglycemia (250-400 mg/dL). Prognosis is better than true hepatic HE if the horse survives the acute encephalopathic phase.
High-YieldMorgan weanlings may develop hyperornithinemia, hyperammonemia, and normocitrullinuria syndrome - a genetic condition causing episodic HE. Consider this in young Morgans with recurring neurological signs.
| Stage |
Clinical Signs |
Clinical Notes |
| Stage I (Mild) |
Subtle behavioral changes, mild depression, decreased appetite, lethargy |
Usually missed in horses. May be exacerbated by feeding (postprandial HE). |
| Stage II (Moderate) |
Disorientation, inappropriate behavior, persistent yawning, mild ataxia, aimless walking |
Horse may retain hay in mouth without chewing. Circling behavior may begin. |
| Stage III (Severe) |
Marked confusion, aggression, head pressing, circling, blindness, profound ataxia, somnolence |
Horse becomes dangerous to handle. May self-traumatize. Maniacal behavior possible. |
| Stage IV (Coma) |
Recumbency, unresponsive to stimuli, coma, seizures possible |
Prognosis grave. Consider euthanasia if no response to aggressive treatment. |
Clinical Signs and Staging
Clinical signs of HE range from subtle behavioral changes to coma. The West Haven Criteria has been adapted for veterinary use to classify HE severity.
Additional Clinical Signs of Hepatic Insufficiency
- Icterus (jaundice): Yellow discoloration of mucous membranes and sclera
- Photosensitization: Hepatogenic - due to phylloerythrin accumulation
- Weight loss: Common with chronic liver disease
- Colic: May be associated with gastric impaction (common complication)
- Bilateral laryngeal paralysis: Reported in some cases
- Orange/dark urine: Due to bilirubinuria
- Coagulopathy: Prolonged PT/PTT due to decreased clotting factor synthesis
- Dependent edema/ascites: Due to hypoalbuminemia (rare in horses)
Exam Focus: Head pressing is a CLASSIC board exam sign of hepatic encephalopathy. When you see a horse with head pressing + icterus + abnormal liver enzymes, think HE first!
| Test |
Normal Range |
Clinical Significance |
| LIVER ENZYMES |
|
|
| GGT |
Less than 30 IU/L |
BEST screening test for liver disease. Elevated with hepatobiliary disease. May stay elevated for weeks even with recovery. |
| SDH |
Less than 8 IU/L |
Best for ACUTE hepatocellular injury. Short half-life (3-5 days). Must be analyzed within hours of collection. |
| AST |
150-400 IU/L |
Non-specific - also elevated with muscle damage. Interpret with CK. |
| FUNCTION TESTS |
|
|
| Bile Acids |
Less than 14-20 micromol/L |
BEST indicator of liver FUNCTION. Greater than 30 micromol/L = liver failure. No fasting required in horses. |
| Ammonia |
13-108 microgram/dL |
Supports HE diagnosis but poor correlation with severity. Sample must be chilled and analyzed rapidly. |
| Bilirubin (Total) |
1.0-2.0 mg/dL |
Elevated in liver failure. Distinguish from fasting hyperbilirubinemia (normal GGT). Direct/conjugated fraction elevated in cholestasis. |
| Albumin |
2.5-4.0 g/dL |
Decreased with chronic disease due to impaired synthesis. Long half-life makes it insensitive for acute disease. |
| Glucose |
75-115 mg/dL |
May be low (impaired gluconeogenesis) or high (stress). Monitor closely - hypoglycemia rare but serious in adults. |
| PT/PTT |
Species/lab dependent |
Prolonged with severe disease. Check BEFORE liver biopsy. Factor VII has shortest half-life, so PT prolonged first. |
Diagnostic Approach
Diagnosis of HE requires demonstrating both neurological dysfunction and hepatic insufficiency, while ruling out other causes of encephalopathy.
Laboratory Testing
High-YieldLiver ENZYME elevation indicates liver DISEASE. Bile acid elevation indicates liver FAILURE. A horse can have markedly elevated GGT but normal bile acids if sufficient functional hepatic mass remains. Conversely, horses with portosystemic shunts may have high bile acids with near-normal enzymes.
Diagnostic Imaging
Abdominal Ultrasound: Essential for evaluating liver size, architecture, and identifying biliary abnormalities.
- Normal liver: Homogeneous echogenicity, less echogenic than spleen, visible portal vein walls
- Fibrosis/cirrhosis: Increased echogenicity, small liver, rounded margins
- Cholangiohepatitis: Dilated bile ducts, hyperechoic foci (cholelithiasis)
- Acute hepatitis: Hepatomegaly, decreased echogenicity
- Hepatic lipidosis: Marked hyperechogenicity, rounded margins
Liver Biopsy
Liver biopsy provides definitive diagnosis and prognostic information. Perform ultrasound-guided biopsy at the right 12th-14th intercostal space. Check coagulation profile (PT, PTT) before biopsy.
Histopathologic findings by etiology: Pyrrolizidine alkaloid toxicosis shows megalocytosis, bile duct hyperplasia, and periportal fibrosis. Theiler disease shows massive hepatocellular necrosis. Cholangiohepatitis shows neutrophilic infiltration of biliary structures.
Differential Diagnosis
Other causes of encephalopathy must be excluded:
- Equine Protozoal Myeloencephalitis (EPM)
- Cervical vertebral malformation (Wobblers)
- Eastern/Western/Venezuelan Equine Encephalomyelitis
- West Nile Virus encephalitis
- Equine Herpesvirus-1 myeloencephalopathy
- Rabies
- Lead toxicosis
- Idiopathic hyperammonemia (non-hepatic)
- Leukoencephalomalacia (moldy corn poisoning)
| Treatment |
Dose/Administration |
Mechanism/Notes |
| AMMONIA REDUCTION |
|
|
| Lactulose |
0.1-0.2 mL/kg PO q8-12h OR 333 mg/kg PO q8h |
Non-absorbable disaccharide. Acidifies colon to trap NH3 as NH4+. Cathartic effect removes nitrogenous material. First-line therapy. |
| Neomycin |
4-10 mg/kg PO q8-12h for 1-2 days |
Kills urease-producing bacteria. Risk of diarrhea/dysbiosis. Use short-term. Give via dose syringe - avoid NG tube if coagulopathic. |
| Metronidazole |
15 mg/kg PO q12h |
Alternative to neomycin. CAUTION: Hepatically metabolized - may accumulate. Neurotoxicity can mimic HE. |
| Mineral Oil |
2-4 L via NG tube |
Decreases ammonia absorption, facilitates removal. Use cautiously with coagulopathy (NG tube bleeding risk). |
| SUPPORTIVE CARE |
|
|
| IV Fluids + Dextrose |
Balanced crystalloids with 5% dextrose at 2 mL/kg/hr |
Correct dehydration/acid-base imbalances. Dextrose reduces catabolism and ammonia production. Monitor glucose to avoid hyper/hypoglycemia. |
| Sedation |
Low-dose xylazine or detomidine |
Required for dangerous horses. Use lowest effective dose - hepatic metabolism impaired. Avoid respiratory depression and head-down position. |
| Mannitol |
0.5-1.0 g/kg IV over 20 min |
For cerebral edema. Less pronounced in horses than humans. Consider in severe HE unresponsive to other treatment. |
| NUTRITION |
|
|
| Diet Modification |
Low protein, high carbohydrate. Grass hay preferred. Small, frequent meals. |
Reduces ammonia production. Avoid alfalfa (high protein). BCAA:AAA ratio important. Maintain caloric intake to prevent catabolism. |
Treatment and Management
Treatment goals: (1) Control neurological signs and ensure safety, (2) Reduce ammonia production and absorption, (3) Support hepatic function and regeneration, (4) Treat underlying cause.
NAVLE TipWhen a horse with HE needs oral medication, give it via dose syringe mixed with molasses - DO NOT pass a nasogastric tube unless absolutely necessary (gastric impaction). Nasal bleeding in a coagulopathic horse with HE can be difficult to control and swallowed blood worsens encephalopathy by increasing gut ammonia.
Prognosis
Prognosis depends on the underlying etiology, extent of hepatic damage, and presence of fibrosis. Key prognostic indicators:
- Good prognostic indicators: Improving liver enzymes, decreasing bile acids, return of appetite, resolution of neurological signs within 72 hours
- Poor prognostic indicators: Severe/bridging fibrosis on biopsy, persistent HE despite treatment, coagulopathy, globulins greater than 45 g/L, bile acids greater than 50 micromol/L
- Survival rates: With appropriate supportive therapy, approximately 40% of horses with hepatic disease survive at least 6 months. Horses with neurological signs have poorer prognosis than those with only biochemical abnormalities.
Recovery from HE is possible if the underlying hepatic disease is reversible and sufficient functional hepatic mass remains. The liver has significant regenerative capacity if hepatocyte loss is gradual and fibrosis is minimal.
Memory Aids
"AMMONIA" - Causes of Equine HE
- A - Alkaloids (pyrrolizidine - ragwort)
- M - Metabolic (hyperlipemia)
- M - Miscellaneous toxins
- O - Obstruction (cholelithiasis)
- N - Neoplasia
- I - Infection (Theiler disease, cholangiohepatitis)
- A - Anomaly (portosystemic shunt)
"HEAD PRESS" - Clinical Signs of HE
- H - Head pressing
- E - Encephalopathy (altered mentation)
- A - Ataxia
- D - Depression/Disorientation
- P - Persistent yawning
- R - Roaming aimlessly
- E - Eye changes (blindness)
- S - Somnolence/Stupor
- S - Self-trauma (maniacal behavior)
"LACT" - Treatment of HE
- L - Lactulose (trap ammonia)
- A - Antibiotics (neomycin/metronidazole)
- C - Carbohydrates (dextrose IV, low protein diet)
- T - Tranquilize if needed (low-dose alpha-2)