Let's Talk Liver Disease

For Episode 13, we want to talk about liver problems in dogs and cats, and give you an overview of the potential causes of liver disease, some of the solutions, and some of the thought processes that go into figuring out how to determine which cases need a big workup, what are the potential pathways that we can go down, and try to chip away at this very confusing, but super common topic to affect the health of dogs and cats.

So as a very broad overview: a lot of you all are going to have a conversation at some point with your veterinarian that your pet's liver enzymes are abnormal. And as an extremely brief overview of that, all we're seeing are liver enzymes that are elevated in the blood that indicate that there's some part of the liver cells that are unhappy, and undergoing some degree of damage, and those enzymes are leaking into the bloodstream and we're picking those up when we check the blood.

They mean different things based on different enzymes, and whether it's a dog or cat, and the severity of the enzyme elevations will provide different information. In general, in a dog, we have three different categories of things that can cause liver enzymes to be elevated. And that is: 1) hormonal conditions such as Cushing's disease or hypothyroidism, 2) primary liver disease, which includes about a dozen different problems that can affect the liver on a primary basis, diseases that are actually happening in the liver itself, and 3) secondary liver disease, which is the bulk of our dogs that are dealing with abnormal liver enzymes. That is because the primary condition is in the gut, and the liver in that way functions as a big lymph node in the abdomen, draining all of the blood that goes to the intestine. If there's something wrong with the intestine, usually inflammation, the liver is going to take the brunt of that and be secondarily inflamed, and release those enzymes into the bloodstream.

In cats, they don't quite have the same story. Cats usually, when they have elevated liver enzymes, it's primary liver disease. Occasionally, you'll have a situation where you have a secondary component, but that is not as common. And the causes behind the liver enzyme abnormalities in a cat are going to be different. So we'll save them for last because cats are special and they're the cherry on top of our story today.

That's the 30,000 foot view on liver disease. Probably 80 to 90% of our dogs are going to have secondary liver problems. A very small percentage, probably 5% at the most, of our dogs overall that have elevated liver enzymes are going to have primary liver disease. And then the rest of them are going to be hormonal. And in cats, it's complicated, of course, because they're cats.

So let's dive into a little bit of this and I'm going to give you a primer on the liver enzymes and how they work, and then we'll go deeper into the potential causes.

Abnormal Liver Enzymes

At any rate, you do your labs, we give you a call and say: “Your pet has an abnormal liver enzyme". So let's talk about what the significance of that is. Let's go through some of these things. The most common liver enzyme that we're going to see abnormal in a dog is going to be alkaline phosphatase. We also call this ALK Phos. Alkaline phosphatase is a nonspecific liver enzyme, which means that it comes from places other than the liver. So we can see this elevated from one of the most notorious things. Maybe something that people think about a lot is with cortisone, and that can be external cortisone that we're doing via a pill or some other medication. Prednisolone or prednisone is a common one that will cause this. But, internal cortisone called cortisol, that's coming from the adrenal glands and it can also cause this to be elevated.

And that is actually an interesting wrinkle on this enzyme situation that those things cause elevation of an isoenzyme. And the isoenzyme is not exactly the same as alkaline phosphatase, but the machine sees it as the same result. So it's not exactly ALK Phos, but the machine is going to spit it out as ALK Phos.

I'm getting a little deep in the weeds already, but one of the things that can cause that ALK Phos to be elevated is Cushing's disease, which is too much cortisol coming from the adrenal glands, or externally because of medication. It seems like there's some degree of knowledge out there with some of our clients on that side of this.

Alkaline Phosphatase aka ALK Phos

Alkaline phosphatase is an enzyme that we'll see elevated in a dog, and there are other liver enzymes. ALT, which is the more common enzyme that we see elevated in cats. It's frequently elevated in a dog. It's probably the most important liver enzyme that we see. And that is because it's a primary liver enzyme. So it only comes from the liver. It doesn't come from anywhere else. Those are from the actual hepatocytes or the liver cells that are leaking this enzyme into the bloodstream, and we're picking it up when we take the blood. So we'll get back to that.

There's a couple other enzymes that are minor players: AST, which is another nonspecific liver enzyme. So we can see that coming from muscle tissue. And then we have GGT, which is a special liver enzyme. That points to a particular area of the liver associated with: the bile system (aka the Biliary system), the gallbladder, or inside the liver itself, the biliary tree or the cells that are actually secreting bile. So that's a bile avenue that we go down.

The only other liver test that is really just a liver test is called a bile acids test, which is a liver function test. And then we have some liver associated tests that can be things that go up or down depending on liver function. So I'm going to back up.

Let's say your dog has an elevated ALK Phos in the blood test. We are going to call and have this conversation, and we're going to say there are three potential categories of things that can cause this particular enzyme to be elevated. And I would say this stands true for a cat with an elevated ALT, and a dog with an elevated ALT, and a dog with an elevated AST, and maybe we can throw GGT in there to some extent, although that deserves its own little special conversation. So primarily, it's ALK Phos and ALT in a dog.

We look at three different categories within this: hormonal causes, primary liver disease, and we look at secondary liver disease. So let's talk a little bit about the hormonal causes in the dog.

Hormonal Causes

Cushing's disease and hypothyroidism are the main ones that we think about. Cushing's disease is extremely complicated and it deserves its own podcast episode, so look for that as a future offering by us. But Cushing's disease briefly is an overproduction of cortisol, which is natural cortisone from the adrenal glands. 15% of the time that that happens in dogs, it comes from a primary adrenal tumor. So the adrenal glands are little, teeny tiny glands that are next to the kidneys. Adrenal glands produce hormones. They are told to produce hormones various ways. The part of the adrenal gland that produces cortisol is told to do that by the pituitary gland in the brain.

So 85% of the time that we have Cushing's disease in a dog, it's going to come from a pituitary tumor that is producing too much adrenocorticotropic hormone, aka ACTH. So, it's producing too much ACTH and that's stimulating the adrenal gland to produce too much cortisol. That's going to cause that ALK Phos potentially to be elevated. And, that can happen and affect ALT as well. So that's Cushing's disease as far as the potential contributor.

There are some common symptoms associated with Cushing's disease. So when we're having this conversation, generally we'll ask if you are seeing any of those common symptoms. The four common symptoms that we see with Cushing's disease in a dog are: 1) drinking excessive water, 2) producing a dilute urine. So you're going to have a higher volume of urine that's being produced. Potentially your dog is going to stand there for a longer amount of time urinating and producing a larger pool of urine. 3) increased appetite. That could potentially be something that you're not going to notice if, say, you have a Labrador retriever that wants to eat everything under the sun, you're not going to probably know when there's an increased appetite because it's relatively high all the time. But some dogs will really go crazy for this.

I've had people bring their Cushing's dogs in for diagnosis because they are really causing havoc at home. They're breaking into the kitchen cabinet, and they are getting the food out of the cabinet. I have had dogs present with this symptom that have taken cans of food (literally a tin can), and the owner comes home and the cabinet is open, and these cans are just flattened because the dog has actually taken the can in its mouth, punctured the can, gotten everything out of the can, and squished the can with its jaw, basically getting every speck of food out of the can. Crazy stuff. These dogs truly and literally go insane with hunger. Oftentimes those are dogs that have pituitary tumors and those tumors are potentially pushing on things, making the dog extra hungry. But an excess amount of cortisol can do that.

Then the 4th and final symptom is panting at rest. So you'll find that your dog may potentially not be in a hot environment and will be sitting there panting. Panting is a really tough one to pin down because there are a lot of different potential causes for excess of panting in a dog. The most frequent cause is anxiety, and anxiety is going to be secondary to something. Typically that might be pain. That could be some sort of illness. A dog that is nauseated or a dog that is extra itchy, potentially will pant because of anxiety associated with the symptom that's underlying that. But the Cushing's dogs will just pant excessively because of metabolic changes that have happened inside their body, and that is all associated with the excess of hormone from the adrenal glands.

The other hormonal problem that we see is hypothyroidism. So that's a low thyroid hormone coming from the thyroid glands, and that's not an uncommon problem in dogs. It's extremely rare in cats, but in dogs it's relatively common. This is the typical issue that we see in people as well. The mechanism of why hypothyroidism causes alkaline phosphatase to be elevated is still complicated and a little bit confusing, and I am not going to go in depth on that here. But know that that is one of the potential conditions that can cause that ALK Phos to be elevated in a dog.

Half of the time, Hypothyroidism, by the way, is going to have completely no symptoms being noticed at home. Nothing seems to be wrong with your dog. And some of the time you're going to have the classic thing where you have an overweight dog who can't lose weight, who's very low energy overall, maybe a poor coat, maybe some skin problems, not necessarily itchy, but some skin problems can be going on. Skin infections, flaky skin, yucky dull coat. But a lot of times there's nothing to see there. So we diagnose that a lot of the time as a surprise to people as well. And oftentimes when we supplement them with hormones, people notice that there's a big difference in their overall energy level and the dog's back on track.

So we can sometimes get some hints of this and we're having our conversation with you that, "Oh yes. Over the past six months I've noticed that my dog is really, really hungry and panting a ton, even when it's in an air-conditioned house. Yeah, there's actually a lot of water that's being consumed. I'm filling the water dish up more frequently." So, some of these things can be obvious that they might be contributing in that hormonal bucket.

With some of the things that we see with Cushing's disease, we’ll also be able to determine based on lab work. So sometimes when we do the labs, we can say that Cushing's disease is not likely at all because the urine is very concentrated or something else along that line. So all of that falls within the hormonal bucket.

Primary Liver Disease

Then the next bucket is primary liver disease. And this would be, I think, what most people think when they are being told that their dog has a liver enzyme abnormality is that the primary liver disease is what's going on. But that's actually less than 10%, maybe 5% of the actual dogs that have elevated liver enzymes will have true liver disease.

So, with primary liver disease, something happened directly in the liver. So our common things in dogs are chronic active hepatitis, which is inflammation of the liver. That is not a viral cause like it is in people. This is an inflammatory condition. Oftentimes it's linked to other things going on in the gastrointestinal tract. You can also have cancers of the liver. So if you have cancer of the liver, even if it's benign, it potentially is angering some of those liver cells. And when the liver cells are angered and they're undergoing some degree of damage or inflammation, you will have the enzyme leak into the bloodstream and then you're going to pick that up.

You can also have degenerative changes. So there are several different types of degenerative conditions that can happen to the liver of dogs. And they're all a little bit different, but there's some degenerative changes. Then there are some issues associated with the gallbladder that will affect the surrounding liver cells, and that's not just GGT that's going to be elevated with a gallbladder issue, but potentially just ALT or ALK Phos.

So with primary liver disease in dogs and an ALK Phos that's elevated, oftentimes that pushes us in the direction of the biliary tract, although not entirely. Again, GGT is the special one that would really help with that. GGT is not on every blood test, by the way. So if we were to do a mini panel that doesn't include GGT, we're not going to have that particular enzyme being measured. One of the benefits of doing a more comprehensive panel is we get more information about the liver, in particular. But if GGT was elevated and ALK Phos was elevated, we would have concerns about the dog's biliary tract, which would be the gallbladder and everything that leads into that.

At any rate, ALK Phos can give us a little bit of a hint on that as well with primary liver disease. There are about 12 different conditions, minimally. There are some really rare ones too, of course, so the list actually goes on a lot longer than that, but there are a number of different conditions that are primary liver disease.

And these are things that are all treated differently to some extent. So you don't have a “one size fits all” as far as medicine goes with primary liver disease, and those are all things that would really be determined by a liver biopsy. So we'll get there. That's about the bulk of the story with primary liver disease as it pertains to an ALK Phos.

Secondary Liver Disease

Our third category is secondary liver problems, which certainly we'll see ALK Phos elevated with this as well. And this is our most common problem that we see causing liver enzyme elevations in dogs. Secondary liver problems are going to typically relate to a primary cause of intestinal disease, and usually intestinal inflammation. And usually, that intestinal inflammation is coming in the form of inflammatory bowel disease. In a human, this would often be called Crohn's disease, which is a chronic inflammatory condition of the gut. So, if you have inflammation that's happening in the gut, your main lymph node in your abdomen is going to be your liver. Your liver does lots of different things. One of its functions is to function as a big lymph node. And if your intestine is inflamed, your liver will be secondarily inflamed and then you're going to see those enzymes light up.

So with ALT, which is a different enzyme, we will often see a similar type of causation behind that, where you have the same three buckets still in play. But ALT is going to be less commonly associated with Cushing's disease. It can happen, but it's not the common enzyme. Hypothyroidism, again, is not as common as ALK Phos being elevated, but it can happen. Primary liver disease: this is where we see the ALT almost always elevated because ALT, remember, is a primary liver enzyme. So it oftentimes will be elevated in a primary liver condition because the liver cells are undergoing some degree of damage from the actual condition that's happening in the liver itself.

Let's use Hepatitis as our good example for this. You have inflammation in the liver. That's going to cause death of cells. When the cells die or are damaged, they're going to release that enzyme into the bloodstream and we pick it up. So that is very commonly associated with primary liver disease.

Secondary liver disease, we actually have quite a bit of this as well. And that's really because the end result is the same. You have the root problem in the intestine, but the liver is dealing with that. So the liver ends up being secondarily inflamed, and then you have cellular death and damage, and release of the enzyme into the bloodstream. So that's ALT.

So, let's talk a little about AST, which again can be elevated with muscle cell damage. We don't see this a lot, but occasionally you'll have, let’s say: a Labrador that comes in who has exercise-induced rhabdomyolysis. "Myo" means muscle. So rhabdomyolysis is where the muscle cells undergo damage during exercise, and they break apart, and they then spill their enzyme into the bloodstream. And that's a bad thing for a Labrador to have; that's a genetic condition typically. It can frequently happen to dogs that are active... including, but not secluded to, hunting dogs. It's basically an overexertion thing. But it's not just overexertion. It's going to be a special version of overexertion in a particular individual that is potentially going to then spin them into having a severe problem with their liver. You have to do something with these muscles when they get broken down and damaged that then filters through the entire system and causes all these secondary issues. There's very, very few dogs that we see with rhabdomyolysis. But another potential cause of that AST being elevated would be muscle damage. Most of the time, it's actually coming from the liver. That is going to fall into those same categories that are going to cause it to be elevated.

And then you have GGT, which is much more specific, like we talked about before. Could you see it with a secondary liver problem? It's not very likely. With intestinal disease, you're likely not going to have this unless you have some kind of problem with the biliary tract, which can happen because these things are all intimately associated with one another. So the liver is producing that bile and putting it into the small intestine. If you have inflammation in the upper part of the small intestine near that outflow tract from the gallbladder, you can then pinch off that tube and potentially end up with a partial biliary obstruction, which makes it so that the gallbladder can't get the fluid out.

Or, you can have an infection in the intestine, which of course you have bacteria in the intestine all the time. But if you have inflammation that's happening, that's potentially diminishing the body's own ability to fight off infection. And you have an ascending infection that goes from the intestine up through the gallbladder, up the biliary duct, and can infect the gallbladder. And then you're going to have GGT be elevated because the gallbladder's infected or the gall bladder's inflamed, or you have a partial biliary obstruction and the gallbladder is very angry because it can't get that bile out. So there's lots of different ways that GGT can be elevated that has its root in intestinal disease or pancreatic disease.

The pancreas has its own outflow right near the gallbladder's outflow. So all these tubes are all conjoined in this weird, busy intersection. When you have that kind of situation, you have a lot of overflow from a lot of different areas. And that's kind of what happens in that upper part of the small intestine called the duodenum. That's where all those tubes come into play. And if you have disease in the upper part of the small intestine, which is not unusual in a dog, you potentially have interplay of all these things.

It's so complicated. It's actually "fun" as a veterinarian to figure this stuff out. And we are ready for the challenge, by the way, at Alicia Pet Care Center. But, it is very complicated. So it's impossible (as you can probably tell) to give a lot of information. That's why, when I have these conversations, I will tell people the extent of my knowledge at this point is that the liver is not happy about something. That's what we know. We don't know what the problem is. We typically won't know what the problem is unless we do extensive diagnostics, which we don't always do. And that is really dependent on the individual patient's struggles and whatever limitations are put on us by pet owners, or whatever the individual case may be.

Let’s Talk Cats

Let's move to the kitties because they are much more simple. A cat can have an elevated GGT, and that is not unusual because they are little bit more likely to have biliary disease. That is because they frequently have inflammatory bowel disease much more commonly than dogs, and that biliary tree can be impacted by that.

More commonly, you're going to see an elevation of ALT -- that's going to be the most commonly elevated liver enzyme in a cat by far. An ALT is going to be elevated most of the time from something called cholangiohepatitis, which is inflammation of the liver. Especially the part of the liver associated with biliary production for the biliary tree. And that is because that is the area that's susceptible to inflammation creeping up from the duodenum and affecting that biliary tract of the liver.

But we will also see ALT elevated in a cat due to inflammatory condition without involvement of the gallbladder. And we can see that with cancers as well. So if you have a 17 year old cat, we don't really love to see elevated ALT's because sometimes that means that there's a tumor that's growing in the liver itself.

And we can also see that the other liver enzyme, alkaline phosphatase is elevated in a cat. And that is almost always associated with something called hepatic lipidosis; the common term for this is "fatty liver syndrome". That's a condition that happens to cats when they are not eating. If a cat tries to produce energy from fat in its body, it has to go through this process that's very complicated. It basically turns its fat into energy via the liver. When a cat does this, it does it in a very particular way, and it will clog the liver up with these fat cells. That will impair the ability of the liver to function. The liver basically gets clogged up with fat, and that causes a cat to become sick with hepatic lipidosis or fatty liver syndrome.

So most of the time, we can get an idea that this is happening because we've had a fat cat that, for whatever reason, went off of its food and lost a lot of weight. And the owner might be actually excited about that. But we do lab work on them, and oftentimes we do this when they're sick. And we see that their alkaline phosphatase is elevated, which points in the direction of this fatty liver syndrome.

Occasionally, we'll see ALK Phos elevated just as a normal screening tool in cats. It's really uncommon that that's the case. Usually they're sick when they have an elevated ALK Phos as an adult.

We talked about ALK Phos at the beginning of this: remember, it's the nonspecific liver enzyme. One of the things that we can see in our young dogs and cats that are growing is that the alkaline phosphatase would be elevated in a growing bone situation. The bones when they are growing are releasing enzymes into the bloodstream as well. And those alkaline phosphatase elevations in a young, growing puppy or kitten are things that we expect and we blow off because, even though it's falling outside of the normal range, it's very common to see it elevated and it's not really meaningful outside of a normal bone growth situation in a young animal.

The Conversation and Decision-Making Process With Our Clients

So let's say we are having this conversation about liver enzyme abnormalities in your dog or cat, and we've now explained (in an extremely confusing way) that there are a number of different conditions that can cause it to be elevated, and we don't know what it is. And there is a real limitation on our level of being able to interpret these results. We can kind of guess a little bit, but that's dangerous. And so we're going to have a conversation of: “What do we do next?”

Of course, part of that is guided by you. So we really do rely on our pet owners to be historians for us, because we're not at your home. So we need to hear, regarding a dog, let's say: is the poop intermittently soft? Is it a little bit soft every single day? I have found over time that no dog owner is going to call soft stool "diarrhea". They will only call it diarrhea if it's liquid stool. So we have to be careful also about how we ask our questions, because chronic, intermittent soft stool in a dog is the number one symptom that we see with inflammatory bowel disease. And if we have inflammatory bowel disease going on, we very well might get a secondary liver problem happening and see this elevated liver enzyme.

So when we ask the question how is the stool, we are not asking it just so you can say everything is great. We want to hear the real report that's happening at home. Because if we have an inkling that we might have inflammatory bowel disease going on, that's going to change the way that we're going to approach that particular case. So it's important to be very critical.

It’s All About The Poop

Just as a side note, you really should be expecting a normal poop from every dog every time. We are going to release a new episode shortly called “It’s All About The Poop”, so keep an eye out for that. In the meantime, let's talk about the idea of "normal" poop. I think we all kind of know, I guess we assume that we all know what normal poo is. It should be dense and easily picked up with no residue. Color's not so important; it's the consistency of the stool. So it should be a nicely formed, dense stool, that doesn't leave a residue when you pick it up. It's not really extra moist. It doesn't squish easily when you pick it up, you're kind of like picking up a soft serve ice cream cone.

So we will go down this question & answer sort of situation and determine what the next step is. Oftentimes, we're going to want to prove a second data point. I think, if the dog is not sick or the cat is not sick, maybe in a cat it's a little more meaningful in a cat if we see liver enzymes, so we might move quickly. But if we see that the enzymes are elevated, we might wait a beat and recheck that enzyme in 1-3 months, something along that range. It's a little bit up to the veterinarian's discretion. And if we get a second data point, we see that those enzymes are elevated again, the important part is not that they are a little higher or a little lower, it's really that they're persistently elevated. So if we see that they're elevated again, we're going to have a deeper conversation of, "Well now what do we do next?"

So what we do next is really going to be up to the team making this decision with whatever limitations, philosophies, urgency from the veterinary side… all of those things in mind. Not every dog is going to get a full liver workup. I would hazard a guess that the vast majority of them are not going to get a full liver workup, at least not at Alicia Pet Care Center. This is because we are a very results-oriented practice. So we have found at the beginning of the story of us determining patients having liver enzyme abnormalities, we have determined that not every single one of these needs to be worked up fully. Oftentimes you have a dog who has a mild liver enzyme elevation throughout its entire life with no clinical significance.

But every dog is different. Every situation is different. So we have to operate in a way that is going to protect the group against having those rare situations come to a higher level, and us losing our opportunity at minimizing progression and creating a disease state.

Different Tools To Dig Deeper Into Liver Issues and/or Abnormalities

So, our next move might be that we want to look at that individual's liver with an ultrasound. And if we do an abdominal ultrasound on a dog or cat, we're going to be able to evaluate all of the liver, the gallbladder, the intestines, the stomach, the pancreas, and the rest of the organs in the abdomen. But those are the big things. Those organs are all going to relate to potential liver enzyme abnormalities that we might pick up.

So that's a great tool because it's a noninvasive tool. It doesn't require anesthetic, it's not going to require surgery or anything like that. Most of the time it's not going to require a sedative for that pet. So it's a pretty good test, like an x-ray. It's relatively easy to do and relatively easy to interpret. It's a little more complicated to interpret than an x-ray, but our doctors at Alicia Pet Care Center are all highly trained in ultrasounds. So we should be able to give you a pretty good idea of what's going on based on our doctor staff performing the test and giving you that feedback.

Some of the things that we're going to be able to determine on an ultrasound right off the bat are: 1) is there a lesion in the liver that we can see inside the actual structure of the liver? 2) Does the gallbladder look normal or not? 3) Is the biliary tree, the part of the liver that leads up to the gallbladder, or the biliary duct that leads from the gallbladder out to the intestine, are those things normal? 4) Is the liver small, or is the liver big, or is the liver misshapen, or is there an obvious tumor? Those are all things that we'd be able to determine on an ultrasound.

Now, there are massive limitations to ultrasound. And with the liver primarily, there is a big limitation because you can have advanced disease in the liver and not have any structural changes on the liver that the ultrasound would pick up. So it is not a perfect test. It's going to miss some things.

We can also look at the pancreas. So if the pancreas is abnormal, we're going to see that on the ultrasound, and it's going to look a couple of different ways depending on what the actual problem is with the pancreas. We're going to be able to look at the small intestine. This is an important thing as it pertains to intestinal disease. If you have inflammatory bowel disease, there's a good chance that your intestine wall is going to be thickened because of inflammatory cells that have gradually added on top of each other in the intestinal wall. So that may cause intestinal wall thickening that we would also be able to determine based on an ultrasound in a dog or cat.

And, we may be able to determine that there are no abnormalities associated with either one of those things, which puts us into a position of breathing a sigh of relief, potentially, that we don't see anything. So we just gradually keep watching these enzymes, unless our patient is acting sick.

So that's one thing that we can do to flesh this out a little bit more. One of the other things that we can do is called a bile acids test, which is a liver function test. The liver function test tells us just that: what is the function of the liver? Is it normal or is it abnormal? And if the liver function is abnormal, if the bile acids test comes back abnormal, that is concerning because the liver has a lot of redundancy. Just like our intestinal tract, there's a lot of redundancy there as well. But with the liver, if you were to chop out a third of the liver surgically, you would have no negative consequences of doing that. Which reflects this redundancy thing that we talk about, which means that you can have a lot of disease in the liver and still have a very functional liver.

So, if you have an abnormal bile acids test, it does put a little bit of a fire underneath you to figure out what is going on, because this condition is so significant, that it's now affecting the function of the liver. And I'm extra concerned about that because the liver has a ton of redundancy.

The bile acids test is not going to tell you what the problem is, but it may tell you how severe it is and may push one case or another to do more definitive testing to find out what the actual issue is.

The main test that's going to tell us exactly what's going on in the liver with primary liver disease is a biopsy. And we are in a great place at Alicia Pet Care Center now to obtain liver biopsies because we can do that with our laparoscopic surgery equipment.

Our doctor team is fully trained for laparoscopic surgery. This is a very routine and relatively easy procedure to perform with laparoscopic equipment, where you now are making a very small incision in the abdomen. It does require a general anesthetic, but you're able to go in with a camera, visualize the outside of the liver. You obviously can’t visualize the inside of the liver; you're doing that with ultrasound primarily. But you can go and look at the outside of the liver with your camera and determine exactly where you want to take that biopsy. You can see that you're doing it very safely. You can obtain that biopsy and a very nice-sized sample that the pathologists are appreciative of, not having these tiny fragments to work with.

So, we'll get a great quality biopsy sample, and we're going to be able to determine with the camera viewing it the entire time that there is no problem with bleeding after the fact. If we do have a little bit of bleeding, we can use a blood clotting sponge that we can put in there with the laparoscopic equipment. And then, again, monitor and make sure that the liver is not continuing to bleed. So that's an excellent way to get a liver biopsy.

There are two other ways of getting a liver biopsy that are not as preferable to laparoscopy, because they're either more invasive or they're more dangerous / also not giving us a great sample.

So the more invasive way to do it is with an abdominal exploratory surgery, where you're going in surgically and you are taking chunks of the liver out with your hands and instruments. The benefit of doing it that way in certain cases is that we can also do intestinal biopsies at the same time if we have a concern that we might be dealing with intestinal disease as the primary condition. As stated before, this is a really common scenario. So, that is not necessarily a bad test. It's a more comprehensive test, and it actually might tell us a lot more than just getting a simple liver biopsy in certain cases.

The other way of doing the liver biopsy is to do it via ultrasound guidance with a biopsy needle. The biopsy needle goes in externally. Usually the patient is heavily sedated for this. And the biopsy can be monitored through the ultrasound and directed towards a specific area of the liver. Then your biopsy is a core biopsy, which is a little worm fragment taken from inside the liver. This can work out relatively well, but you do have some potential downsides of: sometimes your sample quality is not great, because you're blindly going in. It's not entirely blind cause you can see it with the ultrasound, but it's not perfect. You can have bleeding, and the bleeding is problematic because you're not in there, you're not able to actually do anything externally except for just monitor it with the ultrasound. And you're also not entirely able to visualize the area that you want. Because with liver disease, oftentimes you have widespread disease so you're not able to actually see anything other than the internal structure of the liver with the ultrasound. Sometimes, you can see that there's a lesion there. And quite honestly, sometimes we get a little scared about sticking a needle into a lesion in the liver without being able to see what's going to happen afterwards. So there's some risk associated with a guided biopsy of the liver via ultrasound with a needle. There's some potential for not getting the samples that we want, and there's potential for some negative consequences from taking that sample itself.

Liver Shunts

That's primarily it as far as diagnostics go for the liver, aside from something that we might do in particular breeds and particular circumstances. One of the things that we haven't talked about yet is something called a portosystemic shunt, or a liver shunt. These are special circumstances that tend to happen in particular breeds. So we think about the Yorkie as the number one breed for this condition. The Yorkshire terrier has a very high risk genetically of developing a liver shunt. A liver shunt is a blood vessel that was supposed to go away when the embryo developed that did not go away. It takes blood away from the liver when it's coming out of the intestinal tract.

So normally, what happens is: blood vessels (like we talked about before)… the blood goes from the intestine to the liver back up into the circulation. That works really, really well for life because the liver is going to detoxify the things that are coming out of the intestines. It's going to break down waste products and toxins, in a way of working as a filter and a detoxifying organ. But that's not allowed to happen because the blood vessels didn't go away. So this blood vessel potentially stays there and shunts blood away from the liver. And now the liver is not able to do its job. So we have a consequence from that: generally, our young patients have toxins that are going straight to the brain instead of going through the filter of the liver. So it will cause potentially neurologic disease in a younger patient; it can make them have ataxia, which is incoordination. They can be very dull, and they're basically being poisoned all the time, a little bit, from their own body because the liver is not able to do the normal job that it's set up to do because the blood is not getting to it.

So there's a really great test for this that can be done at one of our neighboring specialty hospitals up in Tustin that's called a shunt scan. It is a radioactive enema. This is sometimes called a “tech scan”. The technology is called technetium, and it is radioactive. So, you put this radioactive substance up into the colon. The normal liver is supposed to be taking that out of the intestine through the blood, through the vessels that lead straight to the liver. So in a normal patient, you would be able to see this radioactive marker on a computer screen that's assessing the radiation in the patient. It goes into the colon, and then it goes up to the liver and then it goes back up into the heart. But in a patient that has a liver shunt, the liver just gets bypassed. It just goes straight into the colon because we put it up there, and then it goes straight up into the heart and bypasses the liver entirely. You can see this in the monitoring equipment that's looking at these radioactive markers that we just put up in there.

Now, rest assured, it's not dangerous to do this process. This is a benign radioactive material that is just excreted, and no bad things happen to the individual patient. But it's a great test for a shunt. We're actually very lucky in the country to have a facility so close to us that does this because a lot of the country has to travel hundreds of miles to get to a specialty center that would offer something like this. But we have it right in our backyard. It's a really quick and easy way to get to the answer of: "does my dog have a shunt or not?"

There are other things that we can do for diagnosing a shunt. Usually what happens is: your puppy has an abnormal liver enzyme. Oftentimes, this is being done prior to a spay or neuter. And we see the ALT is five times normal. Let’s say you happen to have a three-pound Yorkie, maybe that's also doing some odd things at home by acting a little weird, especially around meals. After a meal, it gets a little quiet, a little lethargic. Maybe it's having more symptoms than that. But we immediately say okay, we need to do a bile acids test on this dog before we spay it because we're going to put anesthesia in that's going to have some degree of an effect on the liver. We don't want that to happen, because the shunt patients will potentially take two days to wake up from their anesthetic event. That's one of the big reasons why we do blood testing in regards to an anesthetic patient, because the liver is going to play a big role in detoxifying all the anesthesia that we put in.

At any rate, we're going to do a bile acids test on that patient and the numbers are going to come back super high, typically. Because the liver is not functional. Remember, the liver is not getting blood flow. So not only is it not able to do its job, but it's also not getting nutrients that it needs to be able to successfully grow and be a healthy organ. So the liver function is going to be bad and your bile acids are going to be almost always relatively high.

If we have that scenario play out, then we're going to send a young dog up for a shunt scan up to Dr. Broome in Tustin. Dr. Broome is going to do his shunt scan and he's going to call us back and say: "Your patient has a liver shunt." So that's the story of shunts in a puppy.

Quick reminder, we got to liver shunts because we were talking about bile acids being abnormal.

Cats’ bile acid will be abnormal relatively infrequently because they usually don't have such severe disease, that it actually causes them to go into liver failure. But remember, the bile acids test is a liver failure test or a liver function test. And so some dogs that have primary liver disease will have, at the end of their liver disease playing out, significant decrease in function because they've eaten up their liver cell's normal abilities to do their normal thing.

We sometimes get ourselves into a situation where we have very difficult decisions to make. With liver disease, I think it's especially challenging because much of the time, we don't know what the actual problem is. And that's because much of the time, we're not going to do a liver biopsy because the patient's symptoms don't necessarily warrant it. Maybe we measure these liver enzymes over a period of 6 to 12 months and we see that they don't really elevate all that much above the mild elevation that they had. Or maybe they fluctuate and they normalize, and then they come back up again. And maybe our patient doesn't really seem to care whatsoever. We don't want to get lulled into a place of complacency because that can end up biting us in the butt. But we also don't want to do a liver biopsy on every single patient because there is some risk associated with that test. So we don't want to paint every single patient into the same place. They're all different. And it's all very complicated.

With liver disease, especially, we have to practice veterinary medicine as an art. A lot of this also has to do with our owner limitations. So if we have a financial restriction, that's going to limit what we can do test-wise. It is also really common for us to have an owner that's having a hard time getting their head around this. Honestly, I understand this a lot. People look at their dog, the dog is totally normal. And the ALT might potentially be 600 and it shouldn't be above 130; it's a super high number. And maybe the patient is walking around like nothing's wrong. It's going to be very difficult for most owners to say: "Let's go and spend $400 to do an abdominal ultrasound, and go pursue a laparoscopic liver biopsy at a cost of several hundred dollars." Most people are not going to want to do that unless there is a significant reason to do so. So, we have to balance out the search for knowledge based on our patient's needs and what the likelihoods are and our clients' hopes, dreams, desires, limitations.

So it's super complicated, as you can tell. And we are only scraping the surface here. There's so much to talk about with various liver diseases. In theory, a whole podcast episode could be done on cholangiohepatitis in a cat or copper storage disease issues in a dog.

It’s Extremely Complicated

I think the main takeaways that we want you to get with this podcast is that it's extremely complicated. It is not necessarily the end of the world to get your pet diagnosed with a liver enzyme abnormality, but it is also something that we can't blow off. It's something that we have particular treatments for based on the individual diagnosis that is made if we get to the point of making a solid diagnosis.

I think the thing that I would want to leave with is a discussion about liver supplementation because that is oftentimes what we end up doing, in a dog especially. Oftentimes, again, the best we're going to be able to do is to say that we know that there's something that's making the liver unhappy about things. And we (our doctor team at Alicia Pet Care Center) don't want to get super aggressive. The client doesn't want to get super aggressive at diagnosing the liver problem itself. So we're not going to get a liver biopsy done. We might not be able to do a bile acids test. We might be put in a position where our monitoring is not happening as often as we would like. And the patient potentially is not showing any degree of illness associated with this.

The nice thing about the liver is that we can actually play this supplementation card to enhance the special things that we have about liver cells. And one of the things that's special about the liver is that it's like a lizard's tail, where it can regenerate. Besides the fact that there's a ton of redundancy, a cool thing about the liver is that its cells can actually regenerate. So if we set the liver up to improve its health, we're going to have the potential of helping that liver regenerate itself and protecting ourselves against chronic degeneration of the liver that eventually can lead to a very bad situation where we don't have a whole lot of functional liver cells left.

Liver Supplementations

So we think about three different categories of liver supplementations as well. These are all evidence based things, which means that there are studies that have been done multiple times to prove that these are very effective moves that can help with the liver cells being more healthy and being able to regenerate themselves.

So those three liver supplements are Omega-3 fatty acids, milk thistle, and SAM-e. So we'll start with SAM-e. SAM-e is an amino acid that has various properties, but one of the things that it does is it helps the liver cells be more functional. It decreases inflammation mildly in the liver, and stabilizes the cell membranes. So it resists ongoing damage to the liver. Interestingly, SAM-e in people has lots of different uses including treating depression. So it actually can do a lot of different things. One of the things that I would say about SAM-e is that it's one of the more expensive products that we're going to use. And, ideally (it doesn't always have to happen this way), it's given on an empty stomach. So most of the SAM-e is going to want to get to the mid-intestinal zone. And it can only do that if it's not being digested in the stomach.

Once you feed a pet, there are all of these digestive enzymes that are going to be released from the pancreas and from the gallbladder. All of these things that are happening in the stomach and upper small intestine that are going to break things down, we don't want that breakdown to be happening there. So we want to try to slide into the mid-intestinal zone so that the product can actually be taken up there rather than being broken down and digested in the stomach and upper small intestine.

In my own personal practice [Dr. Matthew Wheaton], and I don't mean Alicia Pet Care Center, because we're all a little bit different in this: I will save SAM-e for my patients for last, because I think it's a little harder for the client to do this particular supplement because the timing is important and it's a little bit more expensive.

I like going with Omega-3's first, and that's because it's also going to help with a lot of different areas of the body. So Omega-3 fatty acid supplementation absolutely deserves its own podcast. But that is a product realm that can help almost every cell in the body improve its function or health. So everything that ends in 'itis', every inflammatory condition. So gastroenteritis, hepatitis, arthritis… all of those inflammatory conditions will be helped by Omega-3's because Omega-3's are natural anti-inflammatories. They also stabilize cell membranes and decrease ongoing damage to cell walls. They have some degree of an antioxidant property to them as well. So, there are a lot of cool things that come from Omega-3's. So you're not going to only get your effect in the liver, but you're going to get it all over the place. And if you have a situation where we have intestinal disease as our primary condition and our liver is taking the brunt of that; then again, Omega-3's are a great choice because you're going to get anti-inflammatory on both ends of the problem.

Omega-3's, again, deserve a long talk. But the really, really brief statement on this would be that fish oil is a middle of the road choice. It would be an affordable choice for dogs and cats to get Omega-3's from fish oil. They're readily available. They're pretty affordable. You are going to be getting primarily DHA and EPA out of that and it's easy to do.

The stronger Omega-3 is going to be from green-lipped mussel oil. Briefly, on green-lipped mussel oil, you are dealing with a much stronger anti-inflammatory because of the spectrum of Omega-3's that are in green-lipped mussel oil. Green-lipped mussel comes from the sea creature in New Zealand and there are 18 different Omega-3's associated with green-lipped mussel oil and they are going to be produced in a low heat environment. So it's going to maintain the structure of those long chain fatty acids.

And maybe most importantly, there is a fatty acid called ETA that is coming from green-lipped mussel oil that's found nowhere else in the world (as of yet) that is very, very similar to something called arachidonic acid. So that is the thought of why it likely is much better on the anti-inflammatory side: it is potentially being substituted into the inflammatory cascade instead of arachidonic acid. So, ETA becomes a very important Omega-3 that is only found in green-lipped mussels. Omega-3 is definitely a helpful move and something that is potentially going to provide widespread benefits.

Milk thistle would be our third supplement that we would think about. And milk thistle is, again, affordable. It is pretty widely available, although you're going to find different forms of it. We have a great supplement here that comes from an organic farm up in Montana. Milk thistle is a product that has been around obviously for an extremely long time. Indigenous population has been using this as a liver supplement since probably prehistory times. And it just does really cool stuff for the liver cells in that it decreases inflammation, increases the ability of them to regenerate and heal, and is a very benign, safe medication that doesn't have to happen on a particular time schedule like the SAM-e does.

Oftentimes, what's going to end up happening is we're going to identify that the liver enzymes are abnormal. We may do some additional testing. If we don't do a liver biopsy, frequently the end result is that we're going to use liver supplementations and ongoing monitoring to determine what the next move is. If we move somewhere else to do more diagnostics, that's probably going to take the form of either doing an abdominal ultrasound or a bile acids test. Either one of those tests may lead us to doing a liver biopsy, which is where we're going to actually find the real cause of the liver enzyme abnormalities themselves; that is very occasionally done. But that would tell us the full story.

And this is why we love looking at our blood tests when we get to work in the morning. If we did maybe half a dozen wellness labs on our patients the day before, when we get in we look at our labs almost as our first thing. We commonly will see that we have two or three dogs that have abnormal liver enzymes. We get relatively frustrated because we feel compelled to give our clients the answers to their questions and to give them a clear understanding of what's going on. And, much like so many things in this world, it's very complicated. So we feel compelled to have some degree of this conversation.

Hopefully this podcast will serve as a resource for pet owners to get an extended version of that talk. Potentially even for pets that we are not actually vetting across the world. But hopefully, this has been helpful to you all to understand the complicated nature of liver enzyme elevations and what they might potentially mean, and how to deal with them.

Question from podcast host: "I know that I've had my understandings from the outside world of liver issues and maybe not so much as with animals as with humans. But can you talk about: what about the people who get very yellow and they're very sick when they have liver issues. Is this not something that carries over to the animal world?"

Dr. Matthew Wheaton's response: That's a great question. We do have that in dogs and cats, but it has to be advanced disease. Generally, that can happen actually from things that are not liver problems. So your red blood cells can break apart and cause that same kind of thing. But if it's liver disease, you will potentially become jaundiced. So you've likely heard that word: jaundice. It's sometimes used with babies. I think that's the most common thing that we hear about is "my baby was born jaundice and I need to do those special UV lights". That's a whole different thing entirely. We don't deal with that at all in dogs and cats.

But you can become jaundice with end stage liver problems. That's really bad. So when we have a patient that comes in yellow, it's usually a very advanced liver condition that's going to be difficult for us to actually get back to normal. We may be able to manage that patient for a time, but usually those are our more severe liver problems. And generally it reflects, unfortunately, conditions that have been allowed to progress for a long period of time and they've just eaten away the function of the liver over time. And then you have liver failure in the area of the biliary tree, and you get a buildup of those 'dyes', so to speak. It's different colors that happen that the liver is supposed to be taking care of, and then your body will show that yellowy color. It's very bad in a dog and cat to have that sort of thing show up. Because it's now so late in the game. A lot of times there's not a lot that we can do to reverse the problem and we end up just managing that end stage liver disease patient for as long as we can based on their quality of life maintaining “okay”.

The symptoms are tough because they're usually very vague. The most common thing is that you're going to see chronic intermittent soft stool with a dog that reflects intestinal disease, that then reflects back on the liver and you get a secondary liver problem. Beyond that, unless your dog is extremely sick, you're probably not going to know that there's liver disease going on at all. So symptoms are tough. Most of the time, this reflects an owner that is allowing for us to do our normal annual wellness panels and finding these markers before the clinical symptoms come.

Question from podcast host: "I have a friend of mine from years ago whose dad died of cirrhosis, and you didn't really mention that at all. Is cirrhosis even something that goes on with pets?"

Dr. Matthew Wheaton's response: It is. Cirrhosis actually just really means “scarring”. So you can absolutely have cirrhosis of the liver in a dog or cat. That is going to end up being a very bad scenario, again, because you're going to have scarring in the liver. And that's typically an end stage liver disease sort of scenario. There's different conditions that can lead to cirrhosis in people and in animals. But in people, the vast majority of it is going to be related to alcoholism; you're just basically damaging your liver cells all the time. They're functioning as a toxin remover, but you're killing them and doing it in a consistent way. If you're an alcoholic, and let’s say you're drinking every single day, potentially, and never really giving your liver a chance to regenerate. So you just destroy your liver that way.

It can also happen secondary to inflammation. So, on the human side, another cause for cirrhosis would be any of the hepatitis viruses. So there's different types of hepatitis in people, but hepatitis means inflammation of the liver. So you have a chronic smoldering inflammatory condition of the liver that's caused by a virus.

In dogs and cats, it's not typically viral. We actually have vaccines against those things that are routinely done. That's another reason why you want to stay on top of your vaccines. Beyond that viral cause are inflammatory causes. And those are a very high cause for our primary liver disease patients to present. Dogs and cats having hepatitis are common types of primary liver disease. If you have hepatitis that's going on for a long period of time, you eventually will take away the ability of your liver to function properly because you have replaced liver cells with inflammatory cells. And you now have scarring that results from that, and you end up with a cirrhosis scenario and typically a yellow patient.

The podcast host: "Well this is all, as you said, extremely complicated. I didn't realize, personally, what we were walking into as we started this episode. And I feel like I understand it a lot more. I know that we already have some of these things planned to go into other podcasts, and I think we've opened up a couple more that we now know we need to record. So I will tell you all: make sure you look at the list of our different episodes so you are linking some of these things together.

Thank you to Dr. Wheaton for taking this time out of one of your days off to educate us on liver disease and liver enzyme abnormalities. I know that this will be a huge resource for a lot of people. Like you said, potentially not just patients that we are vetting in the hospital… but pets around the world."

Dr. Matthew Wheaton: I hope that it's going to add to your normal veterinarian's talk that maybe was confusing to you. Because, again, I feel really bad having these conversations with people because we're trying to dump literally two years of physiology and specific learning that we have obtained on liver conditions into an owner's brain in, hopefully, no more than 15 minutes on the phone. It's really challenging to do that. So hopefully this will be an added resource to a lot of people out there to enhance the conversation that you've already had with your veterinarian and to be able to understand it a little bit better.

Okay, and that is the end of this episode on liver disease. Thank you so much for joining us. We hope this answered a lot of your questions and provided some extra clarity. If you have more questions or if you have more topics that you want us to discuss, send us a line. You can drop us an email at: wecare@mypetsdr.com. You can also contact us through social media.

You can find Alicia Pet Care Center on Instagram, Twitter, Snapchat with our username @APCCvet. We are on Facebook as Alicia Pet Care Center. You can send any questions and topics you'd like us to discuss on a future episode to wecare@mypetsdr.com. Our hospital's website is www.mypetsdr.com and the podcast website is www.PetTalkPodcast.com.

The podcast is available on the Apple native app, and for you Android users, it’s available on Google Play and the Stitcher Radio app. You can share those with your neighbors, or friends, or family members that may be dealing with any of these issues as well.

Thanks for listening!