Hepatic Encephalopathy

What is hepatic encephalopathy?

Hepatic encephalopathy is a condition that occurs when the consequences of liver disease affect the brain. When the liver does not work properly, certain chemicals in the blood change and disrupt normal brain function. The exact process is not completely understood, but a buildup of ammonia in the blood appears to play a major role. Increased blood ammonia is toxic to nervous system cells.

What causes hepatic encephalopathy?

Hepatic encephalopathy is usually associated with a portosystemic shunt (PSS), a condition that prevents blood from being filtered by the liver. Certain breeds are more likely to be born with a PSS. Dog breeds predisposed to PSS include Yorkshire Terriers, Old English Sheepdogs, Irish Wolfhounds, and Cairn Terriers. Persian cats and Himalayan cats also have a higher incidence of PSS. Hepatic encephalopathy can also occur with acute liver failure and with severe liver disease, such as hepatic lipidosis in cats.

What are the clinical signs of hepatic encephalopathy?

The clinical signs of hepatic encephalopathy vary and may appear shortly after a pet eats. Signs include:

• Dullness or decreased alertness
• An unsteady gait
• Heavy drooling
• Crying or whining
• Muscle tremors 
• Sudden blindness
• Pressing the head into objects
• Seizures

The underlying liver disease may cause additional signs, including:

• Weight loss
• Decreased appetite
• Jaundice (yellowing of the whites of the eyes and gums)
• Vomiting
• Diarrhea
• Increased urination

Hepatic encephalopathy can be classified into five grades of increasing severity, ranging from Grade 0 (no obvious clinical signs) to Grade 4 (severe lethargy or coma).

How is hepatic encephalopathy diagnosed?

Your veterinarian may suspect hepatic encephalopathy based on your pet’s medical history, physical examination findings, and laboratory test results.

Blood and urine tests. Affected pets may be anemic (have a low red blood cell count) or have abnormal blood test results, including elevated liver enzymes, high levels of bilirubin (a pigment released from red blood cell breakdown and excreted by the liver), high kidney values, low albumin (a protein made by the liver), low glucose, and electrolyte abnormalities. A urinalysis may show abnormally dilute urine, caused by increased thirst and urination associated with the disease, as well as ammonia crystals and excess protein.

If your veterinarian suspects liver disease, a pre- and post-meal serum bile acid test may be recommended. This test measures the concentration of bile acids in your pet’s blood before and after a meal. Your veterinarian may also recommend testing your pet’s blood ammonia level, although the ammonia level can sometimes be normal in pets with hepatic encephalopathy.

Diagnostic imaging. Radiographs (X-rays) can show whether your pet has an abnormally large or small liver, an enlarged spleen, biliary tract changes, or abdominal tumors. Your veterinarian may recommend an abdominal ultrasound to assess the liver and abdomen more closely. An ultrasound may identify a portosystemic shunt or other liver abnormalities. More advanced imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI), may be recommended to look for changes associated with hepatic encephalopathy or to rule out other causes of your pet’s clinical signs.

Liver sampling. Cytology (a small sample of cells taken with a needle) or a liver biopsy may be recommended to further assess the liver disease. This biopsy may be performed at the same time as the ultrasound, using the ultrasound to guide an instrument into the abdomen to obtain a sample. In some cases, your veterinarian may instead recommend a surgical biopsy of the liver. The collected sample will be sent for assessment by a veterinary pathologist.

How is hepatic encephalopathy treated?

Ideally, treatment is directed at resolving the underlying cause, but this is not always possible. Medical treatment focuses on managing the signs and reducing ammonia levels. 

Reducing ammonia and controlling neurologic signs

• Lactulose traps ammonia in the gut, preventing absorption into the bloodstream. It also increases defecation frequency, moving ammonia out of the gastrointestinal (GI) tract more quickly so it cannot be absorbed. It is often given orally but may be given as an enema in emergency situations.
• Certain antibiotics, including ampicillin, metronidazole and neomycin, may be given to reduce intestinal bacteria that produce more ammonia.
• Seizures may be controlled with anticonvulsant medications, such as levetiracetam (Keppra®) or phenobarbital.

Nutritional management

Although low-protein diets have been recommended in the past because they can reduce ammonia concentrations, it is now recognized that low-protein diets may have negative consequences. Nutritional recommendations have shifted toward providing highly useable proteins and avoiding proteins that promote increased ammonia production by certain GI bacteria.

Lower protein may be recommended initially, but it is generally returned closer to normal once the patient is stable. Ideally, consult a veterinary nutritionist for recommendations specific to your pet.

Emergency treatment

Pets with acute (sudden) severe hepatic encephalopathy may require hospitalization for emergency treatment, including:

• Intravenous fluid therapy to maintain hydration and electrolyte balance and lower blood ammonia levels.
• Mannitol or hypertonic saline if cerebral edema (swelling in the brain) is present.
• Enemas to remove substances produced by bacteria in the colon, preventing their absorption into the bloodstream.
• Treatment of underlying conditions, such as hypoglycemia and urinary tract infection.

Liver support

Your veterinarian may recommend medications and supplements that help protect the liver, including:

• S-adenosylmethionine (SAM-E)
• Vitamin E 
• Milk thistle 
• Ursodeoxycholic acid

These treatments are thought to decrease ongoing liver inflammation and damage and help keep the remaining functional liver tissue healthy.

What is the outlook for pets with hepatic encephalopathy?

The long-term outlook depends on the severity of your pet’s liver condition and the ability to treat the underlying disease.