Hepatic Encephalopathy

By Krista Williams, BSc, DVM, CCRP

What is hepatic encephalopathy?

Hepatic encephalopathy (HE) is a neurologic condition that develops secondary to liver disease. When the liver cannot work properly, it causes changes in blood chemistry that alter normal brain function. Although all the changes are not completely understood, high levels of ammonia, which are toxic to cells of the nervous system, appear to play a major role in the development of hepatic encephalopathy.

What causes hepatic encephalopathy?

HE is most commonly associated with a portosystemic shunt (PSS), a condition that prevents blood from being filtered by the liver (see handout “Portosystemic Shunt in Dogs” for more information). HE can also occur with acute liver failure and with severe liver disease, such as hepatic lipidosis in cats. As hepatic encephalopathy is prevalent in pets with PSS, commonly affected dog breeds include Yorkshire Terriers, Old English Sheepdogs, Irish Wolfhounds, Cairn Terriers, and Beagles. Cat breeds with higher incidences of PSS include Persians and Himalayans.

What are the clinical signs of hepatic encephalopathy?

The clinical signs of HE are varied and may appear shortly after a pet eats. Pets may seem dull, have an unsteady gait, drool heavily, and seizures may occur. Some pets will cry or whine, experience muscle tremors and/or sudden blindness, or might press their heads into objects. The underlying liver disease may cause weight loss, decreased appetite, jaundice (yellowing of the whites of the eyes and gums), vomiting, diarrhea, and increased urination.

There are five grades of HE that range in increasing severity from Grade 0 (no clinical signs) to Grade 4 (severe lethargy, coma).

How is hepatic encephalopathy diagnosed?

Your veterinarian may suspect HE based on your pet’s medical history, physical examination findings, and laboratory test results. Affected pets may have elevated liver values. They may also be anemic (low red blood cell count) or have other abnormalities seen in their blood work results, including abnormal 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 acids test may be recommended. This test measures the concentration of bile acids in your pet’s blood before and after a high-protein meal. Your veterinarian may also recommend testing your pet’s blood ammonia level, although levels can sometimes be normal in patients with HE.

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

"Cytology or a liver biopsy may be recommended to further assess the liver disease."

Cytology (a small cellular sample 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?

If the condition is severe and acute (sudden), your pet may need intravenous therapy that includes mannitol or hypertonic saline to reduce edema (swelling) in the brain and/or L-ornithine L-aspartate (LOLA) to decrease ammonia levels. Seizures are controlled with anticonvulsant medication, such as diazepam, levetiracetam (Keppra®), or phenobarbital. Enemas may be used to reduce colon bacteria that produce protein metabolites that can be absorbed into the blood worsening hepatic encephalopathy.

Once stable, treatment typically relies on two major components. First, the protein content of the diet is decreased to help lower the quantities of protein breakdown products, such as ammonia, that contribute to the signs of HE. Second, antibiotics, such as metronidazole, amoxicillin, and neomycin, or other medications, such as lactulose, are used to alter the bacterial population within the intestines and further decrease the production of certain protein metabolites, including ammonia. Zinc supplementation and probiotics may also be recommended to help lower ammonia levels. With these measures, the signs of HE can often be minimized.

Hepatoprotective supplements intended to protect the liver may be recommended to treat the underlying liver disease. Examples of commonly used hepatoprotectants include S-adenosylmethionine (Denosyl®, Zentonil®), vitamin E, milk thistle (silymarin), and ursodeoxycholic acid (Ursodiol®). These supplements are thought to decrease ongoing liver damage and help keep the remaining functional liver tissue healthy.

What is the prognosis for pets with hepatic encephalopathy?

Prognosis depends on the severity of your pet’s liver condition and the ability to treat the underlying disease.

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