Hepatic Microvascular Dysplasia

aka

Portal Vein Hypoplasia = PVH-MVD  aka (HMD) , Portal Atresia

Ron Hines DVM PhD

   

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Hepatic microvascular dysplasia is primarily a problem of little dogs - the dependent ones that love to cuddle and love to be spoiled. Like all breeds of dogs, they were created by breeding for a special talent, a special appearance or a special size. Some veterinarians suspect that in the search for tiny dogs, breeders inadvertently picked some that were small for reasons that were not, at first sight, apparent. One was an inability to process nutrients properly as they were carried in the blood stream through their livers.

The cells in your pet’s liver that do that work are called hepatocytes. They make up about 80% of the liver’s weight. Hepatocytes are arranged in circular structures (lobules) with numerous blood channels (sinusoid spaces) separate long lines (cords) of liver cells - much like supermarket isles separate the lines of produce.   For them to perform their diversified functions, those channels need to receive, at their outer lobule border, blood from the intestine that is rich in absorbed nutrients. The also need tremendous blood passage to cleans the body of toxins. Nutrient-rich blood is delivered to the liver through the portal vein that drains the intestines. Liver cells (hepatocytes) also need a lot of oxygen because their high metabolism demands it. When the amount of fresh blood bathing them is insufficient, they cannot maintain their health. That arrives via the hepatic artery.  By the time blood percolates to the center of the lobules, hepatocytes have detoxified unwanted products that were absorbed through the intestine, synthesized a number of blood proteins, produced fatty acids from the carbohydrates in the pet’s diet, converted waste ammonia into urea, and synthesized cholesterol and bile salts and stored sugar (glucose) from the blood in the form of glycogen.

Critical to the liver’s success in doing all that is a proper flow of blood bathing each individual hepatocyte. In MVD blood does not percolate around the hepatocytes as it should. Instead, the blood delivering nutrient and toxin rich blood from the intestine short circuits the hepatocytes and enters the pet’s general circulation.  So whereas portosystemic shunts do the same thing through a large, visible channel(s), PVH-MVD do a similar thing through a multitude of tiny abnormal channels present at a microscopic level. Blood is bypassing your pet's vital liver roles.

Some veterinarians refer to PVH-MVD as “liver shunts” - lumping them in with the large shunts that are visible to the naked eye. I tend to reserve that term for abnormal channels big enough to show up on doppler ultrasound. But when the two are lumped together, they are often called portosystemic vascular anomalies (PSVA).

Toy breeds (Yorkshire terriers, Maltese, Shih Tzu, Border Terrier, Cairn Terriers, Havanese, Miniature Schnauzer, Norfolk Terrier, Papillon, Pug, Smooth Fox Terrier and Tibetan Spaniels, etc. ) seem particularly susceptible to this genetic defect.

Most dogs that carry the MVD trait lead healthy lives. Only a few develop health issues because of it.

If those issues do develop, it can occur any time during their life. All degrees of PVH-MVD exist. The most severely effective become runts. Others might die shortly after birth or go on to become “fading puppies”. On x-rays or tummy palpation, your vet might describe the livers of a severely affected pet as smaller than it should be (=hypoplastic, shriveled/ atrophied, shrunken, underdeveloped liver or liver atresia).

The same tests used to diagnose portosystemic shunts (PSS) are used to diagnose PVH-MVD. To tell which it is, vets rely on the absence of visible shunts during a doppler ultrasound exam to rule out PSS and a liver biopsy to confirm PVH-MVD. Occasionally, both are present.  Of course, the fact that the patient is one of the toy breeds makes all the more likely.

Veterinarians currently have no surgical treatment to cure PVH-MVD and no medications to reverse it. The many “cures” you see sold on the internet are fraudulent; “liver support” products run a close second.  

When pets do experience health issue due to having microvascular dysplasia or portal vein blood delivery problems, veterinarians tend to focus on abnormally high a blood ammonia level as the probably cause. You see, one of the livers jobs that it can’t do well now is to convert toxic waste ammonia, a byproduct of metabolism, into less toxic urea. That high ammonia level is thought to be responsible for the mental issues many of these pets face. It is called hepatic encephalopathy and you can read about it here

However it is not that simple. Blood ammonia levels have not correlate well with the degree of mental issues an individual pet is experiencing. Perhaps the elevated bile acid levels, also found in these pets, play a part in their mental issues as well. Some vets theorize that other unknown toxins that accumulate in MVD cases altered blood amino acids and, perhaps, changes in the brain itself are partially responsible. We really do not know. Much veterinary knowledge trickles in from research aimed a treating human disease. A person facing these issues would likely be offered a liver transplant.

I want to emphasize again that most dogs with PVH-MVD NEVER develop hepatic encephalopathy.

What Signs Might I See If My Pet Has PVH-MVD ?

It might have been smaller than its littermates.
It is probably a finicky eater.
It might have bouts of diarrhea and vomiting without a satisfactory explanation. 
It might occasionally have seizures or fainting episodes (perhaps due to hypoglycemia?) or periods of mental dullness – some call it moodiness.
Thin hair coats are not uncommon.

All of the symptoms I listed could be do to something entirely different that PVH-MVD – even if it documented that your pet carries the PVH-MVD trait. One might confuse the signs of a finicky eater that is just spoiled, has dental problems,  epilepsy, toy breed hypoglycemia, hydrocephalus, inflammatory bowel disease, or simply behavioral issues with hepatic microvascular dysplasia.

A pet might with MVD might have periodic “UTI”s ( this situation is quite rare in PVH-MDV, but when it does occur, it is actually due to ammonium biurate crystals in its urinary tract).

How Will My Veterinarian Decide ?

The most important screening test for PVH-MVD is a blood bile acid test. High blood bile acids are a sign of liver problems. The bile acid test is not foolproof – it will occasionally miss a mild case. The tests are done - one before a meal after a night’s fast (preprandial) and one after a meal (postprandial). Generally, it is the postprandial test that is highest – but not always. In any case, any reading above 15-20 micromoles/Liter is suspicious for MVD when the typical symptoms are present (other liver disease sometimes elevate the readings as well) in a high-incidence breed. The test can be run on kittens and puppies as young as 8 weeks; but should be confirmed again about 8 weeks later.
 
Periodic bile acid tests are not a particularly accurate way to monitor how well your pet’s liver is working over the years. You see, the values vary greatly from day to day – even hour to hour. Of course, very large increases over time are worrisome.  Keeping a log of your pet’s body weight, attitude and energy level along with periodic general blood chemistry screens are a more accurate measure of your pets overall health (albumin level, BUN, Creatinine, and glucose, liver enzymes and perhaps Protein C). See dxme

Blood bile acid levels are usually also high in portosystemic shunts. A doppler ultrasound exam should be able to rule those large shunts out. The next confirmatory test is usually a liver biopsy from multiple portions of your pet’s liver. That can identify the liver changes that point to PVH-MVD. The biopsy might also be able to judge the severity of the problem. If the changes are mild but the symptoms severe, perhaps some of the other diseases with similar signs I mentioned early need to be ruled out.  Some advanced facilities rely on
trans-splenic scintigraphy – a procedure that utilizes radioactive markers to trace blood flow. But diagnosing PVH-MVD beyond a doubt is quite difficult. Veterinarians just don’t have a test that rules the disease in or out reliably. (ref)

Well, How Can I As A Pet Owner Manage This Problem When My Pet Is Showing Symptoms ?

DIET


We know that dogs with PVH-MVD have problems processing the protein they absorb from their meals. So for a long time, veterinarians suggested that the amount of protein that PVH-MVD dogs received be restricted. Similar advice was given to humans whose livers had been damaged by cirrhosis and other diseases. However, human physicians found that their patients with liver problems actually needed more protein, not less. They had a tendency to loose weight due to poor appetite and metabolic difficulties and protein restriction only made matters worse.

Following that lead, pet food manufacturers like Hills and Royal Canin increased the protein content of their “liver support” diets and marketed them based on their low copper level (only helpful in copper storage disease, not PVH-MVD) a “precise blend" of antioxidants to support a healthy immune system and increased flavor and density to tempt picky eaters". 

It is fine for you to feed your dog those diets – if you wish. We all need to feel we are doing all we can. However, there is really no scientific proof that they will be helpful. If, on the other hand your dog lives on table scraps now, those diets are considerably better balanced than what most toy breeds would choose to eat given the chance. 

These diets only prove their worth in end-stage liver failure when dealing with the effects of hepatic encephalopathy. My personal feeling is that any high quality, nutritionally balanced diet is fine for most PVH-MVD pets. What is much more important is that you feed it to your pet in small amounts throughout the day to keep its liver workload down. Some suggest that plant and dairy proteins might be more advisable than meat proteins. I do not know on what evidence that is based.

PROBIOTICS

Some veterinarians suggest probiotics or yogurt for its bacterial content. There is certainly no harm in giving some in moderation if it agrees with your pet. But just like optimal protein content, we just do not know if probiotics have any positive influence on liver function or lessens any of the unwanted products that might overwhelm a pet’s poorly functioning liver.

LACTULOSE

Lactulose is a complex form of sugar that is processed by bacteria in your pet's lower intestine. Besides being a laxative, it draws ammonia from the pet’s blood stream into the colon where it can leave in the stool. So lactulose can definitely be beneficial in pets, and humans, with high blood ammonia due to a failing liver. (ref)   Whether it slows the progress of PVH-MVD or benefits pets with minor cases is unknown. If the tests that your vet used to diagnose the condition improve while on lactulose, that is certainly reason enough to continue giving it. The same goes for dietary modification.

PUFAs ......Polyunsaturated Fatty Acids

Most liver diets have added omega-3 fatty acids. Omega-3 fatty acids, are the ones that tend to be high in oily fish and krill. They are thought to combat inflammation. Although they did not seem to help in humans experiencing liver fibrosis (ref) ,  I would supplement them in the diets of dogs with PVH-MVD because I see no down side in doing so. (ref) With time, fish oils become rancid. Stick with those marketed for humans in high-volume stores.

ANTIOXIDANTS

Diets rich in antioxidants seem conducive to health. Vitamin E is an antioxidant. All pet foods are enriched with vitamin E (alpha tocopherol) – both for their antioxidant effect and as a natural preservative. But it is often DL-alpha tocopherol acetate or mixed tocopherols from synthetic sources that is added to pet foods. So a modest amount of natural mixed tocopherols might be wise. (ref) Excessive vitamin E can cause bleeding. (ref1, ref2)

ACE INHIBITORS

Veterinarians dispense a lot of ACE inhibitors – primarily to pets that have heart problems, and occasionally to those with kidney problems as well. Those drugs increase blood flow and lower blood pressure. Humans take them as well.  The most common one is enalapril.
Your dog’s PVH-MVD revolves around abnormal blood flow within its liver. There is some evidence that giving these products to humans with similar liver disease can slow the process of liver failure. (ref1, ref2, ref3) But I do not know of any veterinarians who have attempted to use them in MVD dogs for this purpose. If you do, . write me

ANTIBIOTICS

These are only of possible help in dogs in which the problem has progressed to hepatic encephalopathy. Of course, the causes of ill health can be complex and your veterinarian might suggest them because of other symptoms your pet is experiencing. Of course, they need to be antibiotics that are considered "liver friendly".

TRADITIONAL VETERINARY "LIVER SUPPORT" PRODUCTS ... Like Denosyl, Denamarin, SAME-E, Silymarin, Milk Thistle, etc.

No one really knows if these products actually benefit dogs with PVH-MVD. As with "liver support" diets; If your dog improves on those products, I would continue to give them.

MORE SCIENTIFICALLY-TESTED HUMAN TREATMENT OPTIONS WHEN LIVER PROBLEMS ARE SEVERE

There is little difference in the tasks that your liver and the liver of your pet need to accomplish. So medications that help humans with chronic liver issues are good candidates for helping our pets as well.

Some forms of liver failure in humans improve or stabilize when patients are given oral Ursodeoxycholic acid (aka ursodiol, UDCA) supplements. (ref1,ref2, ref3, ref4) One study found the compound to be helpful in dogs as well. (ref) They are available as over-the-counter supplements.

A 2016 review found that branched-chain amino acid supplements (BCAAs) relieved the low blood albumin levels and hepatic encephalopathy that sometimes accompanies severe liver disease in people. They seemed to improve the general quality of life as well. You can read that article here.

Rifaximin (Zaxine®) is an oral antibiotic that does not pass through the walls of the intestine easily (It has poor bioavailability). So the majority stays in the intestine where it interferes with the growth of bacteria that are thought to play a part in hepatic encephalopathy. In that way, its effects are similar to lactulose. The two have been given together. (ref)

Propranolol and nadolol (Non- selective beta-blockers or NSBBs) generally used to treat high blood pressure. But they play a part in the treatment of chronic liver failure in humans as well. (ref) Perhaps they might be helpful in some pets with liver issues as well.

 

Be sure your dog drinks sufficient water. When organs like the liver or kidneys are not working at their best, their functional units that are still working can sometimes compensate by processing a larger fluid volume.

 

Dealing with PVH-MVD As Time Goes By

In a dog with no symptom of PVH-MVD, its generally sufficient to check their biochemical status (particularly liver function test)  - every 12 months. Do so more often when the dog is loosing weight or shows other health issues. Blood bile acids seem to go up and down on their own. That probably reflects changes in the amount and type of food consumed, the timed emptying of the pet’s gall bladder (a recent meal can increase Bile Acid levels) but sometimes we cannot explain the cause of these variations.

Remember that most pets with this problem will lead a normal life and that many of the “teacup” toy breeds share this problem to one degree or another.