Hepatic Encephalopathy (HE)
In Your Dog Or Cat
Not all cases of hepatic encephalopathy are the portosystemic type
Ron Hines DVM PhD
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Hepatic encephalopathy describes a situation in your dog or cat that results from a failing liver. When you pet’s liver is no longer healthy, it looses its ability to detoxify waste materials (eg ammonia, glutamine, ɣ-aminobutyric acid agonists, benzodiazepine-like substances as well as proinflamatory cytokines). Ammonia levels becoming too high in your dog or cat’s blood stream are a major marker for this problem. Ammonia is normally produced by the bacteria in your pet’s intestines and as a normal byproduct of everyday metabolism within your pet's body. Its the liver's job to convert that ammonia into less toxic urea. The traditional explanation of HE is that ammonia buildup in you pet’s blood stream affects the animal’s brain, leading to confusion and mental dysfunction.
The most common cause of HE in dogs and cats is an abnormal blood flow from the veins that drain their intestines. The major vein that does that (the pet’s portal vein) normally leads to the animal’s liver where these toxic wastes are detoxified or re-excreted into the pet’s bile. These abnormal veins are called portohepatic shunts. You can read my rather complex article through the link or just look at a simplified diagram of the problems here. Most are birth defects, but some occur as a result of chronic liver inflammation. Hepatic encephalopathy can also occur when the pet’s liver has been damaged by medications such as Tylenol, sulfa antibiotics, moldy food, toxic mushrooms, artificial sweetener (just xylitol) and a number of poisonous plants. Hepatic encephalopathy can also result from liver damage caused by canine hepatitis, FIP in cats, toxoplasmosis, leptospirosis and neospora infections. It can also occasionally seen in very severe cases or the end-stage results of hepatic microdysplasia.
In dogs, heavy burdens of heartworms (caval syndrome) have been known to cause HE. In cats, it has been associated with abnormally low levels of the amino acid arginine. In some dog breeds, due to a genetically based problem in storing copper. (copper storage disease ref1, ref2 ). In pets with copper storage disease, restricting dietary copper sources can slow the disease process.
You can read an extensive review of the many things that have been linked to the liver failure that can bring on HE here.
Hepatic encephalopathy is somewhat more common in the breeds of dogs and cats that are the most prone to liver problems (portosystemic shunts are a predisposing factor in toy and small breeds of dogs and in Persian cats; English cockers, Labs, Westies and dobies because of their increased susceptibility to liver disease of other sorts).
Humans suffer from hepatic encephalopathy too. The most common cause in us is cirrhosis of the liver and a common cause of that is alcoholism. (ref)
What Signs Would I See If My Cat or Dog Had This Disease ?
Hepatic encephalopathy is a disease that begins gradually. Generally, the first sign that owners notice is the pet’s lack of interest - a sort of preoccupation – as if the dog or cat was contemplating things far away. That can progress to confusion when decisions need to be made and even snappiness when urged to move or perform some task.
Because you know your pet so well, none of these signs might be apparent to visitors or even to your veterinarian. As liver damage increases, some pets become unsteady on their feet and disoriented or “spacy”. That can progress to getting trapped in corners, pressing their heads against objects, blindness, drooling, and even aggression when handled or disturbed. In middle-aged to old dogs and cats, those signs need to be sorted out from early onset dementia. Other owner descriptions of their pet’s changed behavior include wandering, circling, stargazing, pacing, sleepiness, apathy, dementia and compulsiveness.
Signs can progress to prolonged seizures/ convulsions and a semi-comatose condition. Pets with these more critical signs are approaching the end of life. In some, heroic emergency treatment will restore a semblance of normalcy and gain time. But in many, it will not.
In some cats with HE, the iris color of their eyes are said to assume a light metallic color.
Normal liver function is essential for many of your pet's body processes; so a lot of other, non-specific symptoms such as poor hair coat, diarrhea, weight loss and vomiting can occur as well.
It is common for the signs of hepatic encephalopathy to come and go – becoming worse at one time and better at another. That is not the case with things like brain tumors, brain inflammation or hydrocephalus - all of which can result in symptoms similar to HE. Sometimes owners notice that symptoms of HE are worst soon after their pet has eaten.
Are There Things That Might Make The Symptoms Of Hepatic Encephalopathy Worse In My Pet From Time To Time ?
Any form of stress tends to make the symptoms of hepatic encephalopathy worse. As I mentioned earlier, a recent meal sometimes triggers an episode – perhaps because the pet’s body has to deal with more free ammonia produced (indirectly) by the food it ate.
What Test Will My Veterinarian Use To Diagnosis This Disease ?
There are a number of health problems that are not liver-related that could explain some or all of the symptoms your pet is experiencing. Some of the tests your veterinarian might suggest are designed to rule out those other issues.
Things that pet owners describe that might bring HE to your veterinarian’s mind are an unusually strong or persistent effect of tranquilizers and anesthetics (prolonged recovery) or sensitivity to flea and tick products, or medications used to control epilepsy. That is because many medications are eliminated/detoxified by the liver and a weakened liver is inefficient in doing that.
Liver function tests (ALT, Total bilirubin, Alkaline Phosphatase) are indicated. But normal results do not rule out HE. Those tests tend to be high early in liver disease when liver cells are inflamed (leaking) or destroyed, but the test results can be normal when liver problems are long-standing.
Many dogs and cats with failing livers will also have lower than normal blood albumin levels because their liver can no longer synthesize sufficient albumin. Some have reduced blood-clotting factors in tests that measure their blood clotting time (CT, PT,CTG, etc.) because blood clotting also relies on compounds produced in a healthy liver.
Measuring your pet's blood ammonia levels can be helpful in diagnosing hepatic encephalopathy. But the test is quite difficult to perform because ammonia is so volatile (evaporates quickly). So it is a test best performed at advanced institutions familiar with this difficult assay procedure. When your pet's plasma ammonia level is high, it is a good indicator of HE. But some pets with normal reading still have the disease. Also, the degree (amount) that the pet's ammonia level is above normal does not appear to directly influence the severity of the symptoms the animal is experiencing. (ref)
Because of the difficulties in accurately testing for blood ammonia, many veterinarians measure the pet's blood bile acid levels instead. However, like ammonia, normal bile acid results do not entirely rule out HE either.
X-ray, Ultrasound And Other Imaging Techniques
Many pets with HE have a smaller-than-normal liver or liver tissue that has abnormal texture (echogenicity) when viewed with an ultrasound machine. That is due to fibrosis (scaring). There are advanced imaging methods that are excellent for identifying abnormal liver blood flow (as in portosystemic shunts) that account for a large portion of the pets with HE that you can read about here.
Dogs and cats with HE are also at an increased risk of developing urinary tract stones and crystals composed of ammonia compounds (ie ammonium biurate urolithiasis = calculi = “stones”). They can be detected and are generally checked for during imaging exams whenever chronic liver disease is suspected.
Dog and cats brought to their veterinarian in hepatic encephalopathy crisis need intravenous fluids to rehydrate them. They may also need products to coat inflamed intestines - a common finding. Any other life threatening symptoms need to be addressed appropriately. Some dogs and cats with HE are thought to have increased pressure upon their brain. Those pets are often given manitol in an attempt to alleviate that.
Dogs experiencing seizures are often given levetiracetam or sodium bromide. Both are anti-epileptic drugs. Both medications tend to have the potential to cause more worrisome side effects when given to cats than when given to dogs.
If constipation is thought to be a contributing cause to the problem, enemas are useful to solve that immediate problem.
What Long Term Treatments Are Available For My Dog Or Cat ?
The best hope for dogs and cats with hepatic encephalopathy are for those in which the source of their problem is a surgically-correctable hepatic shunt. That surgery is quite expensive. It can only be performed by a limited number of trained veterinary surgeons. It is not always successful and some cases do not lend themselves to surgical correction. Read about that in another article of mine I mentioned before. (ref)
If your veterinarian suspects that a liver infection might be the cause of your pet's liver failure, antibiotics are indicated. Antibiotics (like neomycin and metronidazole) are also thought to be helpful because they reduce the number of ammonia-forming bacteria in your pet’s intestine. So in almost every case of hepatic encephalopathy, they are part of the veterinarian's long-term treatment plan.
Pets with hepatic encephalopathy should avoid medications used to sedate them or they should be given those drugs in reduced doses and the pets then closely monitored. Those medications include benzodiazepines (like Valium), barbiturates (like phenobarbital given for epilepsy or thiopental to anesthetize pets), and narcotics and pain-control medications of any kind. Bouts of constipation, dehydration or prolonged fasting can precipitate (cause) an HE attack in dogs with the problem.
Lactulose, a non-absorbable sugar, is one of the most widely used medications to lessen the symptoms of hepatic encephalopathy. An alternative is lactitol. Both work only in the pet’s intestine and are not absorbed. Added dietary fiber (soluble and insoluble) is also thought to be beneficial. Fiber and fiber fermentation in the dog or cat's intestine may allow more ammonia to leave as ammonium (salts) via the feces. Be prepared for looser stools and/or bloating on all three of these products. Oral neomycin might reduce those problems.
Folks generally believe that neomycin is not absorbed into the body when it is given orally....
But that is not entirely correct. Drugs of that class have the potential to cause kidney or hearing problems. So pets on long-term neomycin need to be monitored (kidneys, hearing, etc.). When neomycin can not be given, metronidazole (Flagyl) at a reduced dose has been used to keep intra-intestinal bacterial ammonia production as low as possible. In humans, rifaximin (Xifaxan) is sometimes given for HE [rifampin as well [ref] . I am told that rifaximin has been given successfully to dogs and cats when neither neomycin nor metronidazole were effective in keeping the pet’s blood ammonia levels under control.
Omega-3 polyunsaturated fatty acids (PUFAs) are thought to reduce inflammation throughout the body. (ref) In experimental systems, these PUFAs also appeared to protect liver cells from the toxic damage caused by abnormally high bile acid levels. (ref) So a krill or cold water fish oil supplement, marketed for humans, might be a helpful addition to your pet's diet as well - particularly if its bile acid test results are high.
You might recall that earlier I mentioned that veterinarians use high ammonia blood levels to confirm that your pet has HE - but that normal ammonia levels do not rule it out. I also gave you a link to a recent article that found that the level of ammonia detected in your pet's blood stream does not correlate well with the severity of the symptoms the pet is experiencing. (rptref) That led some of us to question if high blood ammonia was really the cause (or only cause) of the mental problems your pet is experiencing or if other toxic substances that build up in the blood stream of pets with failing livers might also be involved. One of those other substances are the bile acids your veterinarian used to confirm the diagnosis. Abnormally high blood bile acid levels are also toxic. An interesting experiment was performed in 2016. Mice were intentionally given compounds that caused their livers to fail. Some were fed supplemental bile acids and some where given medications that lowered blood bile acid levels. Those authors reported that the mice fed supplemental bile acids developed mental problems early than mice that did not. They also reported that the medication (cholestyramine aka Questran ® , Prevalite ®) delayed or minimized those problems. (ref) Cholestyramine is one of a group of medications called bile acid sequestrants used in human medicine to lower cholesterol - but also to treat the itching that commonly occurs in chronic liver disease in humans. I do not know of any veterinarians who have attempted to use cholestyramine or similar medications to lower high bile acid levels in HE pets or if they were helpful. If you do, please let me know.
There are other medications that sometimes help humans facing hepatic encephalopathy issues similar to those your pet is facing. You can read about some of them here.
What Would Be The Best Long Term Diet For My Dog Or Cat With Hepatic Encephalopathy ?
Many veterinarians believe that reducing your pet’s protein intake and upping its carbohydrate intake might reduce the symptoms of hepatic encephalopathy. That is because protein breakdown is the source of much of the blood ammonia that plays a part in your dog or cat’s symptoms. But other veterinarians (and human physicians) avoid low protein diets because pets (and humans) can develop malnutrition when fed low protein diets and the protein requirements of ill pets can be even greater than the protein requirements of healthy ones. Those veterinarians simply suggest that the pet’s protein intake not be “excessive”. Pets would probably also benefit from frequent small meals rather than one or two large ones. Once you dog or cat is on medications, its ability handle protein should also improve.
Veterinarians will often also suggest you give your pet antioxidants, supplementation with added vitamin E and/or C, silymarin (milk thistle) and/or s-adenosyl-methionine (SAMe). There is no harm in that.
Other veterinarians suggest that supplying you pet with vegetable or dairy-origin protein rather than protein from meat might be helpful. To the best of my knowledge, none of those suggestions have been scientifically proven to be helpful. Humans, in a similar hepatic encephalopathy situation to your pet would be offered a liver transplant. Your pet does not currently have that option. But there are visionary veterinarians pioneering other options right now. (ref1, ref2)
My personal believe is that it is quackery for anyone to offer to “regenerate” your pet’s liver with fat-derived stem cells. There are companies currently marketing those "treatments" for pets. Although it is the current rage, others have no faith in those procedures either. (ref)
What Is The Long Term Prognosis For My Dog or Cat ? What Does The Future Hold ?
You have to realize that many of the suggested treatments in dogs and cats are, as of 2015, of unproven value in extending the pet’s life and that we have nothing that will regrow or regenerate a failing liver in man or beast. When veterinarians locate a particular, correctable reason for your pet’s liver failure, its options for a long life increase. If you go to the human Wikipedia entry. you will see than many of the standard treatments we veterinarians still use in confirmed cases of HE have been discarded in human medicine as being ineffective. If you pet can be stabilized, the progression of liver failure is quite variable and not inevitable. I have two of the most current diagnostic and treatment guidelines but I can not post them here. Email me if they are of interest to you.