Hello, welcome to the 2nd webinar. We're gonna be talking about feline, liver diseases, and, what's new in the diagnosis, and particularly the management of those diseases. So this is what we're gonna be doing in this session.

We're gonna review the major liver diseases to affect cats. And then we're gonna look at two of the sort of major inflammatory liver diseases that we see in cats being. Lymphocytic cholangitis and neutrophilic cholangitis.

They're relatively common in the UK and they've both got quite different presentations. And then we're going to discuss how we diagnose and how we manage those, and then we'll finish by touching on congenital port of systemic shunts in cats. So just to start, let's have a look at some sort of differences between, cats and dog liver.

So, compared to dogs, cats tend to develop biliary tract disease. So in the previous session we saw that inflammatory parentymal disease was very common in dogs. Chronic hepatitis was the really big one, but cats don't develop that as a disease.

They tend to develop biliary tract disease. So both those two that I've mentioned, on the previous slide, lymphocytic cholangitis and neutrophilic cholangitis. If there's the word cholangitis in there, that refers to the biliary tract.

They don't get very much fibrosis, so they don't really ever develop cirrhosis, and so they don't get all the consequences of cirrhosis you might see in a dog or a human with advanced liver disease. They are more susceptible to drug and toxin induced liver injury than than dogs, so they've got a reduced level of one of the enzymes that's involved in drug, detoxification. They can't synthesise arginine and so it's an essentially amino acid to them, and arginine is part of the urea cycle, so the thing that converts ammonia into urea for excretion.

So, if they've got liver disease and then particularly if they've got reduced intake of food, so arginine, and they can be predisposed to developing high levels of ammonia and so hepatic encephalopathy may only be just subtle signs of that, not those really severe signs. And they require taurine as an essential component in their diet, and that's of course involved in bile acid metabolism. The other big thing that you might remember about difference between sort of the cats and dogs is that.

Some cats get this combination of liver disease, pancreatic disease, and inflammatory bowel disease, and that's what's often referred to as triiditis. It's probably not as common as we think, and I, I, I never like to refer to triiditis as a specific disease, because it isn't a specific disease. I guess it's a sort of a syndrome really, when a, when a cat's got those three different diseases.

As we'll see in a moment, it tends to be a bit more with the neutrophilic cholangitis that cats may get, some cats may get pancreatic disease and, inflammatory bowel disease. And in part that's because of anatomical differences, . So cats have got a, a shared pancreatic duct and billary duct compared to dogs that have got a separate ducts and so dogs are not commonly associated liver disease, pancreatic disease, and IBD.

So this was a study that we did a few years ago now, actually, and, and published in the Journal of Small Animal practise in 2018, and that should be freely available for you to access online. We worked with a very large commercial histopathology laboratory that receives samples from practises all over the UK, mainly primary care practises, I guess there's probably referral practises in there as well. We basically just looked at the submissions from cats that have had liver biopsies to try and determine what sort of liver diseases were out there in the cat population, at least in the UK.

And you can see the various diseases that we identified, and I've sort of put some in slightly light grey because things like reactive hepatitis and reversible hepatocellar injury are not primary liver diseases, and I'll explain in a moment what we mean by that. So important things are that biliary tract disease is quite common, so neutrophilic cholangitis and lymphocytic cholangitis. So a few animals with biliary cysts.

Yes, they develop acute hepatitis, particularly drugs and toxins, and then neoplasia, a poetic neoplasia will be lymphoma, so. Much more common, hepatic lymphoma in a, in a cat than it would be in a dog. You're much more likely to see hepatocellular tumours in a, in a dog.

And then there's one or two other conditions, so, cats occasionally get systemic shunts and other, other tumour types. So, you know, these were, as I say, cats from a sort of a UK general practise population, and these are the sort of conditions which are, which are being diagnosed, which I guess are out there in the, in the cat population. As an aside, you know, we are, as practitioners, taking samples from cats that don't have a primary liver disease.

They have a secondary or reactive liver disease, so reactive hepatitis, which basically means the liver is reacting to something often within the gastrointestinal tract. And so, you I. Ideal world, you know, you want to be determining what that gastrointestinal tract disease is and not taking a liver biopsy, because these patients will probably have, should have slightly increases in liver enzymes.

I suspect that's the reason why they've had liver biopsies taken. So it's always important when we're investigating liver disease to think about this concept of a primary liver disease like neutrophilic cholangitis, lymphocytic cholangitis, or whether it's a secondary or reactive condition. And because the liver has got such a central role in metabolism and it's particularly, you know, philtres the blood that comes from the gastrointestinal tract via that patic portal vein, it becomes damaged with what we call secondary hepatopathy.

So particularly things like pancreatic disease, gut diseases, inflammatory bowel disease, you know, bacterial overgrowth, other types of gas. Gastrointestinal disease, neoplastic disease, and others, you know, of course, cats with endocrine conditions, so hyperthyroidism can get secondary liver damage and get elevated liver enzymes, and that's usually thought to be because the high levels of thyroid hormones are directly toxic to the liver. You see increased liver enzymes in cats with diabetes mellitus because they've got hepatic lipidosis, excess.

Etc. So these are secondary rather than primary hepatopathies, and so it's about good clinical examination, other testing, pattern recognition and things to try and, you know, make sure that these patients with elevated liver enzymes don't have a secondary liver disease before you maybe go on and image their liver and possibly take liver biopsies, but sometimes easier, easier said than done. So what the liver, signs of liver disease in cats, well, unfortunately they are relatively non-specific and so that will also makes the diagnosis quite challenging sometimes.

So lethargy and anapittens, weight loss, vomiting and diarrhoea, PUPD, so we saw those signs when we were talking about, canine liver disease. So they're relatively, you know, non, non-specific. PUPD is not all that common in cats with liver disease, and that may be just because it's quite difficult to, for owners to pick up on increases in drinking in their, cats.

You may see pyrexia, particularly in neutrophilic cholangitis. You may see jaundice in neutrophilic cholangitis. We sometimes see it in lymphocytic cholangitis as well.

And in the ascites as we'll touch on, we see that in lymphocytic cholangitis. Most cats with liver disease, be it acute or chronic, get an enlarged liver. Whereas in dogs, they tend to get an acute with tend to get an enlarged liver with acute disease and a smaller liver with chronic disease, and that goes back to the fact that dogs get fibrosis and cirrhosis, whereas cats don't get significant fibrosis which might lead to cirrhosis.

So when we're investigating the cat with suspected liver disease, you know, we think about history, clinical examination, signalment can sometimes come into it. We'll touch on that in a moment. We normally move on to do clinical pathology, some diagnostic imaging, which is ultimately ultrasonography, and then maybe think about sampling the liver, fine needle aspirate or moving on to do a biopsy, a bigger tissue sample.

Or you may be sort of entering this, this pathway partway through, so maybe you'll do, you know, routine bloods as a health screening or pre-anesthetic check and find that that patient's got increased liver enzymes or maybe you will, you know, be doing an ultrasound scan and find that there's abnormalities of the liver or the biliary system, and that leads you into sort of working out whether this patient has got liver disease and particularly primary liver disease. So you'll remember about, liver enzymes, we touched on them in, in dogs, just as a recap. ALT and AST are markers of hepatocellular damage.

ALP and GGT are markers of bile stasis. Liver enzymes in cats, there's a few important differences when compared to, to dogs. So, ALP and ALT have got very short half-lives, so in the few hours versus in a dog, you know, a day, 2 days.

Very importantly, feline ALP lacks a steroid-induced isoenzyme as compared to the dog ALP. So actually you, you're far less commonly going to see increases in liver enzymes in cats, period, because they've got very short half-lifes, and also, you don't get that stress induced or steroid-induced form of ALP that you're very commonly see in dogs with a whole range of conditions. GGT we may try and look at a bit more in, in cats than we do in dogs.

It's possibly a more sensitive marker of biostasis. So there's gonna be a few more cats that you'll pick up with biostasis because they've got an elevated GGT and their ALP is, is normal, but it's less specific, so there will be some cats that have got increases in GGT that turn out not to at least have any histological evidence of biostasis. So, well, firstly, I, I take note of any elevation of liver enzymes in cats because it's far more likely to point to a primary liver disease, like a poystemic shunt, hepatic lymphoma, lymphocytic neutrophilic cholangitis, the ones we touched on in the earlier slides.

But caveat that it still. Indicates a secondary liver disease like the cat could be diabetic, could be hyperthyroid, could have significant GI disease, but hopefully you will have sort of looked for those other things based on your history and clinical examination. But you may have to do other tests.

So yeah, more likely to suggest a primary hepatopathy. So any increase in liver enzymes in cats should start to ring alarm bells and you should start to be thinking about investigating for liver disease, whereas, of course, in dogs, that's not true, as we mentioned in the last session. We see a lot of dogs with elevated liver enzymes, and they're more likely to have a secondary, so a reactive liver disease than a primary liver disease like chronic hepatitis.

And the other important thing about clinical pathology in cats is because they don't get much fibrosis, they don't get loss of significant function. So unlike in a dog, we don't see evidence of reduced liver function commonly, at least on clinical pathology. So we don't see the classical markers of low urea, low albumin, possibly low glucose.

But they, they can still have elevated bile acids, and that's not because of reduced liver function, but that may just be because of bile stasis. So remember that bile acids will increase with reduced function, but also with bile stasis. So if liver cells swell and bile doesn't move so well through the liver and so you get bile stasis, so that is a cause of bile acids, increased bile acids.

So if you take your dog or cat with diabetes that's got degrees of hepatic lipidosis, swollen liver cells, bile stasis, you will find they've got mild to moderate increases in bile acids and it doesn't necessarily mean they've got reduced function. So yeah, again, the liver diseases that we saw, neutrophilic cholangitis was high up there and lymphocytic cholangitis were the top two primary liver diseases. So let's touch on neutrophilic cholangitis first.

It's occasionally called by other names, so sparative or acute cholangitis, but the correct terminology should be neutrophilic cholangitis. Sometimes you may hear neutrophilic cholangio hepatitis, which basically means the inflammation has spread to the hepatic parenchyma away from just the biliary system. It's seen, at least in the study that we published, in middle-aged cats.

So the median age of these cats was 9 years of age, and in our study, there were certain breeds that were predisposed to this disease. British shorthair, Burmese, Persian, and Siamese, but that's not necessarily going to be the same, in every country or even if studies are done in the, in the same country. So middle age, with certain breeds that are predisposed, but potentially any breed of cat can develop this disease.

It normally presents as an acute disease, so these cats are relatively acutely unwell, a few days, very short history of clinical signs, which often but not always include things like pyrexia, lethargy, anorexia. These cats are relatively frequently, but not always jaundiced, and that's because they can get obstruction, so their biliary tract gets lots of inflammation and neutrophilic inflammation and debris, which can cause obstruction to their biliary tract. So these cats are generally unwell and they've become unwell relatively acutely, and this is quite different presentation to the other disease we'll move on to lymphocytic cholangitis.

So yeah, how do you go on to try and diagnose these cats? Well, you know, you're likely to do in this cat with, you know, non-specific signs and maybe it is jaundiced as well. You're definitely gonna do haematology, biochemistry, and we're likely to see increases in one or more of the liver enzymes we just talked about, but.

Not every cat with neutrophilic cholangitis has an increase in all the enzymes, and in fact, some don't have an increase in any enzyme. It's unusual, but it does occasionally occur, and that might be again, in part because of the very short half-life of these liver enzymes in cats. And then if we're thinking about the sort of two major primary liver diseases in cats, neutrophilic and lymphocytic cholangitis, there's nothing on clinical pathology that differentiates the two.

But you will more likely see increased bilirubin than neutrophilic disease, and, as we alluded to earlier, they're more likely to be jaundiced, and that's because of obstruction, their bili traced by, by debris. You might see a band neutrophilia, left shift neutrophilia, possibly toxic changes to the neutrophils as well. What about diagnostic imaging?

So it can be normal. It's important, important to remember, you don't always see abnormalities, and you may be aware that there's studies out there that actually show there's a relatively poor correlation between the ultrasonographic findings and the ultimate histopathological diagnosis in cats and dogs with a range of liver diseases. And in that study there were animals that had normal appearing livers on ultrasound that had severe disease and conversely, some animals had very abnormal appearing livers and actually had a relatively benign disease.

So, you know, diagnostic imaging, ultrasonography is useful, but you have to remember that there are caveats with it. But anyway, in neutrophilic disease, you tend to see, if you're gonna see abnormalities, they're more likely to be of the biliary tract, so there may be some dilation of biliary tracts, thickness and irregularity of the gallbladder wall, maybe dilation or a tortuous common bile duct, and maybe a bit more likely for the parenchyma to be relatively normal in appearance. So changes to the biliary tract.

What else are you gonna do, maybe around about the time of, anaesthesia, sorry, ultrasonography is possibly take a, sample of bile. And this has been done with a cat that's sedated heavily under ultrasound guidance. It's something you should never do blind, should always be done, at least under ultrasound guidance, if you're, you know, doing an exploratory laparotomy, that's another, obviously very good time to do it, or if you're doing laparoscopy, that's again another good time to do it.

So, ultimately, it's a, it's a way to try and diagnose this disease, but We don't necessarily stick needles in every cat that we're suspicious of having neutrophilic cholangitis. That cat with a, you know, acutely ill, classic presentation maybe jaundice, neutrophilia maybe pyrexic, increased liver enzymes, increased bilirubin if we're imaging and finding some abnormalities to their biliary system, we may have enough evidence that they're likely to have neutrophilic cholangitis. And so we don't stick needles into their gallbladder.

Although the risk is, is very low, the risk of any significant bit of re peritonitis is in the very low single figures in studies of cats and dogs that have had this done, but it's critical that this animal is very still when you do this, because you don't want any movement because of course that could create damage within the gallbladder, gallbladder wall. And this is just an image of it being done at laparoscopy in a, in a cat, so, . Ideally, what you need to do is to try and drain as much of the bile as possible.

That's probably one of the key things to reduce the leak leakage afterwards. So drain as much, as much bile, monitor them afterwards. You will always get a little bit of leakage, but that's always magnified on a video like this, so that's relatively normal, but, yeah, try and drain as much of the bile as possible.

Maybe using, you know, a, a 19 gauge needle, green needle, sometimes it can be quite thick bile, particularly if there's disease in the gallbladder. So yeah, what's the cause of this disease then we said that, you know, these cats are, you know, often unwell and pyorexic and maybe jaundiced and got neutrophilia, maybe a left shift as well. Well, the thought is it's an ascending bacterial infection from the gastrointestinal tract and the majority of these cats have a single species, and it's, it's E.

Coli, but there can be multiple bacteria, found, and there can be cats that have a single bacteria that's, that's not E. Coli, but, the majority of cases do have E. Coli, so that already helps you to decide what Antibiotic to use.

The problem is with all this data, there's studies of very small numbers of cats, and you can see this is one here, which is probably one of the bigger studies of, but still only 44 cats, published, many years, many years ago now. So yeah, how do we, how do we manage these cases? So the other thing I should have said about diagnosis is, you know, taking a bile is, is a nice thing to do.

We uncommonly take liver biopsies from these cats because they are, you know, acutely unwell and they're not a good candidate to have a general anaesthetic and a laparoscopy or a celiotomy to take liver biopsies. If you were to take a liver biopsy, it'd be critical that you assess coagulation beforehand. Some people do that prior to sticking needles into the gallbladder, but I personally don't, but also I would consider doing that if you were to do a fine needle aspirate of the liver, which actually in.

With inflammatory liver disease, it's got a very low diagnostic yield. So unless you're suspicious of lymphoma or primary hepatic lipidosis in a cat, I, I wouldn't do an FNA because it's not good at diagnosing inflammatory liver diseases like like this one. So if you've got sensitivity results from your bile culture, you know what type of you know which antibiotic to use, otherwise you're gonna be using a, you know, relatively broad spectrum one, definitely something that kills E.

Coli. Achieves therapeutic levels in the bile and isn't, you know, activated or excreted by the, by the liver. And so classical ones that most people reach for because it's, you know, commercially available and it's licenced in the UK and, you know, it's relatively safe, it's potentiated amoxicillin.

Unless your sensitivity results say otherwise, I wouldn't reach for a fluoroquinolone as a, as a first line. But if the cat isn't responding to potentiate the amoxicillin, you could then potentially reach to a fluoroquinolone. Occasionally people use men metronizole.

I personally don't. It's quite challenging often to administering cats, particularly over the longer term. And I would treat these cats for a minimum of 4, but probably sort of 66 weeks.

You're probably gonna use other things. So, we mentioned this previously, also deoxychoic acids. It's a great drug.

It's a hydrophilic, water-loving bile acid. It displaces the bad hydrophobic bile acids. It's, it stimulates bile flow.

It's got immune modulatory and other actions. There's no Good data on this drug's use in any liver disease, for that matter, but it's likely to be safe and be effective, so I would, I would use this. The time not to use odeoxychoic acid is if there is suspected complete biliary tract obstruction, which is not that common, but could occur in these cats, so that'd be a time not to use it.

Other things, you know, these cats need to eat because we don't want them developing hepatic lipidosis, but a bunch of them do. So high protein diets, antiemetics, you know, nasalesophageal tube, possibly esophagostomy tube if they're not eating. Again, they need things like taurine, they need things like arginines essential amino acids, so make sure they're eating or use appetite stimulants and other things if they're, if they're not.

Antioxidants might be useful, but for me, I would definitely prioritise antibiotic. Secondly, I would then prioritise usodeoxychoic acid, desylate, and if I was still able to get an additional drug into that cat, then I would consider an antioxidant. They're more likely to be useful in acute disease, and this is an acute disease, but there's no specific studies on them in this disease in cats.

And you know, this is an LA that's maybe being anorexic and vomiting, so you may need other symptomatic supportive measures, some of which we've touched on, like the antiemetics or nasal esophageal or esophagostomy feeding tubes, but maybe you'll need potassium supplementation, for instance, IV fluids, potassium in the IV fluids, etc. They, these cats do sometimes have concurrent conditions. Unfortunately, there isn't very good data.

This is a very old study now looking at the association between inflammatory liver disease in cats and IBD and pancreatitis, but this is, this was published before even the histological standards were out there for neutrophilic cholangitis. So it was caused by called a whole bunch of different names. So, I think the take home is that some of these cats have got concurrent inflammatory bowel disease and pancreatitis.

So, particularly if they don't respond very well or they, they relapse once treatment's stopped or they, you know, develop the disease again, it might be worth investigating or trying to manage concurrent IBD, plus or minus pancreatitis. And the prognosis is relatively good, providing you get on top of their, therapy relatively quickly. They survive for prolonged periods of time, but they can relapse, as I say, and that may be because they're just developing the same disease again or probably more likely they've got concurrent inflammatory bowel disease or pancreatitis.

In that patient, if the serum bilirubin is rising or they become more clinically jaundiced, then it may suggest that surgery is required to relieve a biliary tract obstruction. And yeah, if surgery is required, as you might expect, the prognosis is worse. So that last one was neutrophilic cholangitis.

This is the, at least in our study, the 2nd most common liver disease in cats, lymphocytic cholangitis. Old names were things like non-supperative cholangitis, chronic cholangitis, and again, sometimes cholangio hepatitis is, is used as an alternative and correct terminology. And this has got a very different presentation, as we'll see from neutrophilic cholangitis.

And maybe sort of in, previous texts, it was suggested this was a disease of younger cats, but actually our study looking at quite large numbers of cases suggested that this was, a disease that was diagnosed with a median age of 11 years, so, much older than previous studies. But there's no, at least in our study, there was no good pre predisposition. So this is, as I say, got a very different presentation to neutrophilic cholangitis and that these cats generally remain bright and are well, so they're active, you know, they're going outside, they're playing and things, but, you know, they may be losing weight, they may be polyphagic, they may have variably reduced appetites, they may occasionally vomit, they may have polyurea and polydipsia, but they generally are relatively bright cats.

Significant numbers of them, about 30 or so, have ascites, and that can be a very high protein ascites, and this is just the example of one of the fluids we retrieved from one of these cats with lymphocytic cholangitis. So, high protein content in a, you know, medium to high cell content. And this is a sort of an exudate or a protein-rich transudate, what people used to refer to as a modified transudate.

So that can be difficult to distinguish from, from, FIP sometimes. So yeah, that can be there. Some cats it's just a cat that's, you know, losing weight over time, and is otherwise relatively well, not normally pyrexic.

They've often, but not always, and it might depend how you can examine the cat. They've often got an enlarged liver, on examination, or at least you go on to find one on, you know, images. Or I suppose necropsy, because it's not always possible to do a good cranial abdominal examination in a cat, but because it's a chronic disease and cats with liver disease and chronic disease, the liver tends to swell and yeah, often they've got an enlarged, liver.

Yeah, what about the clinical pathology? Well, similar really to, neutrophilic cholangitis that, you know, many cats are gonna have an increase in, in one or more liver enzyme, but not every single cat, . And they're not, you know, changes in liver enzymes, functional markers, which don't commonly occur, are definitely not sort of pathomonic for this disease.

There's, you know, nothing that separates lymphocytic from neutrophilic cholangitis based on clinical pathology alone. And as I say, not just like lymphocy, just like neutrophilic cholangitis, not every cat is necessarily gonna have an increase in one or more liver enzymes. The majority do, but there are some cats out there that have this disease that have normal liver enzymes.

And then what about the, about the imaging, . They less commonly have abnormalities of their biliary tract. So if you see abnormalities of the biliary tract, particularly if, you know, history, clinical signs fit, then you're gonna be moving more towards neutrophilic cholangitis.

These guys are more likely to have changes to their, hepatic architecture or at least echo texture. So again, a big liver, changes to their echoexture, their hepatic parenchyma. Occasionally see abdominal lymphadomegaly, but just like for neutrophilic cholangitis, the ultrasound can look relatively normal.

And this one is definitely a a condition when you, you know, need histopathology to try and differentiate it. You're not gonna find anything by aspirating bile on these, on these cats, it should be normal, no bacteria in there, no signs of inflammation. So these cats have got increased numbers of lymphocytes, which tend to be T lymphocytes, they've got loss of bile ducts, they've got a little bit of fibrosis and lipogranulomas around their portal system.

Can be quite different, difficult to differentiate from, hepatic lymphoma sometimes. Again, another lymphocyte rich fluids, occasionally from FIP, but of course the macrophage component of FIP should, should help differentiate the two. And yeah, very importantly, don't forget to check coagulation status.

So that's APTT and OSPT or partial thromboplastin time and prothrombin time as pre-biopsy assessment. And if those are prolonged, then these patients need vitamin K. And normally we give the cats.

Vitamin K for 2 days, so 44 doses, and then recheck coagulation, and if it's normalised, get on and biopsy them sooner rather than later. If it hasn't normalised, maybe they need a little bit more vitamin K, but sometimes that's just not enough and they need, you know, fresh frozen plasma and other things to try and get their, coagulation factors back up to a suitable level. So what's about the aetiology?

Well, we don't completely understand the pathogenesis, the sort of histopathology, and particularly the response treatment suggests it may be an immune-mediated cause, but there's lots of studies done and lots of studies to look for signs of, evidence, sorry, of bacteria within the liver of these cats, but, you know, you, you, you do find some bacteria or evidence of. Bacterial genetic material in there, but it's just not, not sure whether it's actually, causal or not in, in these cats. So, yeah, occasionally, as I say, lymphocytic cholangitis, fishes, fluorescent in situ hybridization.

So it's not nec it's not looking for live bacteria. So that is an important thing. Just finding some parts of bacteria in there doesn't mean they're necessarily live, but a few of them do have bacteria are associated with the capsule or the, or the ranula, but We don't still tend to necessarily treat these cats with antibiotics first.

We normally go straight in with immunosuppression, so prednisolone is normally the, the starting drug, and there's a variety of publications looking at this, but quite small numbers, and publications have looked at prednisolone versus ursodeoxychoic acid and shown that Prednisolone is more effective than ursodeoxychoic acid. But, I think these cats probably benefit from having ursodeoxychoic acid as well, if you're able to administer multiple medications to them. So we normally start on about 1 milligramme per kilogramme per day.

There is a study suggesting that, you know, 1 milligramme per kilogramme per day is an appropriate dose and there's no benefit from using 2 mg per kilogramme per day. And we gradually reduce that dose over a sort of about 2 to 3 month period, but some of these cats have repeated bouts of clinical signs, so you may need to restart the drugs occasionally we need to keep using the prednisolone. It's a sort of a, a low, long term, .

Dose so yeah, also dooxyoic acid again. Remember, it's a hydrophilic bile acid, it displaces the hydrophobic bile acids. It has other actions.

There's no data again on its use in this disease, but it's likely to be very safe. These cats uncommonly get any sort of complete obstruction, but if they did have the time not to, not to use it. And we might use other things, we might use antioxidants, Sami-based drugs, but again, it may be that you can't get multiple medications down these, these cats.

Some people do reach for antibiotics because of the concern about an underlying bacterial infection, but I don't think that that is, I don't think that that is, is necessary. Of course, if you start immunosuppressive drugs and the cat worsens, then, you know, you're gonna, you're gonna rethink. If they aren't responding sufficiently to prednisolone alone, then we use additional or alternative immunosuppressants, and the one that's in most texts is carambail.

And then we also make sure that these cats are eating, so it's, relatively critical, of course, cats being cats, so they continue to have protein and have, a high protein, high protein diet. So, yeah, definitely don't, you know, definitely don't, you know, restrict them of, restrict them of protein. .

So, yeah. Those are the sort of things we, we want to use. And you know, these are generally not systemically ill cats that need hospitalisation and things, so they can usually be treated in the outpatient environment.

You know, occasionally they may have reduced appetite and you have to keep them in and support their nutrition. Occasionally we have to remove fluid because there's significant amounts of fluid that might be compromising respiration or compromising . Their ability to eat because of pressure on their gastrointestinal tract, but we try not to remove this fluid because it's high protein fluid and so by removing it, A, it's gonna come back, but B, we're gonna reduce this cat's total body protein.

The fluid is there because it leaks across the hepatic capsule because of the increased oncotic pressure in this big, big swollen liver. So it's not the same reason that we see ascites develop in dogs with liver disease, which is due to portal hypertension. That's not the case in these cats.

Cause again, dogs get portal hypertension when they get chronic liver disease, and fibrosis, which these cats don't get. We don't really understand a lot about the concurrent conditions, that, that these cats have. But there are a couple of studies out there to show, well, one study showed no apparent increase in inflammatory bowel disease in, in these cats, but, again, quite an old study before we had these good histological characterizations of the diseases, whereas another one, a bit more recently did show that a bunch had concurrent IBD and even some had lymphoma as well.

I suspect that the 17% that had non-hepatic lymphoma may, some of them may have also had hepatic lymphoma. It's just that it wasn't differentiated appropriately from lymphocytic cholangitis. So we do need to sometimes do other things to try and differentiate, lymphocytic cholangitis from hepatic lymphoma.

So obviously your histopathology laboratory can, can advise you on that. So as a sort of conclusion to the inflammatory liver diseases section, then we see two, important inflammatory liver diseases in, in cats. We see neutrophilic cholangitis and those cats are generally unwell.

They have, may have pyrexia, there may be jaundice, they've got an acute history of unwellness, . They may have increased bilirubin on their bloods, neutrophilia, liver enzymes, although again not in every species, and imaging they're more likely to have abnormalities of their biliary tract. And to diagnose them, well, taking a liver biopsy would be optimal, but, you know, we rarely do that in this unwell cat that's not a good candidate for general anaesthesia.

So one thing that you could do is take an aspirate of bile and do cytology and bacterial culture of that. And then remember we said that we treat those cats with antibiotics, most likely one that's good at killing E. Coli, and other symptomatic and supportive therapists, particularly osodoxychoic acid, Sami or antioxidant-based drugs could be good, fluids, nutritional support, antiemetics, appetite stimulants, and other things.

And then we talked about lymphocytic cholangitis, so those cats are generally quite well with a chronic disease, nothing that differentiates them from neutrophilic cholangitis on clinical pathology. On imaging, they're more likely to have abnormalities of their parenchyma and biliary system and This is a disease that you diagnose based on liver biopsy, making sure you've done coagulation testing first. Can occasionally be difficult to determine whether a patient's got apatic lymphoma or lymphocytic cholangitis, but there's a variety of immuno immunohistochemistry and other things that can be done to try and differentiate them.

And lymphatic cholangitis may have got an immune mediated aetiology, so it's usually managed with prednisolone, occasionally carambasil, if we don't get a good response. Also the yoic acid is probably good and occasionally other supportive things are needed and of course, correct dietary management is pretty essential in these cats. OK, let's just have a look at this case now, so we'll move on to different liver disease now, away from the inflammatory liver diseases, but continuing with our theme of primary liver diseases.

This is Phoebe, who was a, a young, domestic short hair cat, not being neutered yet, and she was brought to us with a 2 or 3 month history of intermittent diarrhoea and lethargy. And the owner sort of noted some odd behavioural signs. She was hiding, not really behaving like a seven month old kitten you would expect to do.

But on clinical examination, she was pretty bright and alert and, you know, no abnormalities were detected and decided to perform biochemistry and haematology and neuroanalysis as a minimum database looking for systemic or metabolic causes of her signs. And this is a result of the serum biochemistry, so very, very slightly low potassium, maybe decreased intake, increased loss, very slightly reduced urea, which is a bit unusual. Increase alkaline phosphatase, but that could of course come from the bone isoenzyme which, which cats do have like dogs have.

Remember, cats don't have a steroid-induced isoenzyme. A slightly increased glucose, it's likely to be stress, and a mildly increased creatine kinase, which is not likely to be clinically important, probably just suggests some, you know, mild muscle damage, maybe around the time that you've taken the, you know, the blood sample or possibly if the cat's had any sort of intramuscular injections or other things. And yeah, what about, haematology?

Well, you know, relatively, relatively normal. You can see the hematocrits right on the bottom end of the reference interval, so that's something that's just worth, you know, keeping, keeping an eye on, because particularly if you maybe, you know, rehydrate this cat, for instance, it's, number of red cells might, might fall. So yeah, we should definitely keep an eye on that.

The mean opusa volume is, is reduced, that's, you know, a little bit, a little bit unusual. We don't often see that. We might see it in an anaemic patient, associated with a reduction in iron within the red cells, so reduction in MCHC in, of course, iron deficient anaemia, but that's not the case here.

A, because the cat's not anaemic, and B, because the MCHC is, is normal. But we do see microcytic cells, which is what these guys are, if they've got a reduced MCV. In, cats and dogs with, liver disease as well, so, so look out for that.

This urinalysis, nothing too remarkable on there except there's some bacteria in the sediment, but we need to know how that was, collected. But also, we did, and sorry, it's become a little bit out of focus here. We also did, Sediment analysis of the of the urine and saw these which are ammonium urate or ammonium biureate crystals.

So that may start to ring alarm bells if you see those in a, you know, a young cat that's presenting with these non-specific signs, particularly some behavioural signs in there. So, yeah, what further, what further diagnostics could you do? Well, we assess bile acids and this is a good example of when not to rely on just a, a single resting bile acids.

So, the resting pre-randial bile acid in this cat was normal. But we gave it a very small amounts of food. You don't need very much food in these, in these cases.

Don't feed them, you know, super fat restricted food, but we don't need to feed them, you know, a whole bowl of food. They need very small amounts of food really to stimulate gallbladder contraction. And then you can see that the postprandial, so two hour post feeding, sorry, sample was significantly elevated.

So, yeah, just remember about the value of postprandial bile acids. And as we alluded to earlier on, bile acids increase if there is reduced function. If there's biostasis, but the other reason that we didn't say earlier is if there's an anomalous vessel that's taking those bile acids directly from the portal circulation, back into the systemic circulation and bypassing the liver.

So that's, i.e. We see those in animals with a porter systemic shunt.

We can go on and determine that with ultrasonography, although in, you know, small cats it can be quite difficult to see the shunting vessel, just like in big dogs, big deep chested dogs, it can be challenging to find them, or we do, what's thought to be the gold standard, which is CT CT angiogram. So, injecting iodine-based contrast, under the CT to identify the shunting vessel. And as you would expect in a cat or a small dog, this cat was diagnosed with a single extrahepatic portosystemic shunt, whereas your larger dogs are more likely to have an intrahepatic shunt.

So remember, portal systemic shunts were abnormal connections between the portal system, hepatic portal vein ultimately, and the systemic venous pressure. And they take blood coming from the guts directly into the systemic circulation, bypassing the liver. It can be a congenital or acquired.

We're really talking about the we are talking about the congenital shunt in this particular case. Acquired shunts you will see with advanced liver disease, really only in dogs when you get lots of fibrosis and cirrhosis and portal hypertension. And acquired shunts of multiple small shunts, often round about one of the kidneys.

They're ones that shouldn't be surgically managed because there was sort of an escape valve that allows the pressure in the guts in the portal system to reduce. So the congenital shunts then are usually a single, very occasionally a a double anomalous vessel, and again they're either outside the prankima are so called expato, so cats and small dogs, or intrapatic, which you're more likely to see in larger, larger breeds. So in cats, then, as I say, the majority of them are, extra hepatic.

But there are raw, there are some cats that have got intrapatic and just like in dogs, they're divided into, different forms, depending on which liver lobe is, is involved, and I've written those, forms for you there, and that's, very similar to what can be seen in dogs. Yeah, domestic short hairs, make up the, the majority, but they're a common, common breed in many countries, but there might be some breed predispositions to some of the oriental breeds, the Siamese, Persian, Himalayan cats. May have a predisposition and most of these cats present within the first few months of life, but we do sometimes see, you know, middle aged or older animals even with congenital port systemic shunts, both both cats and dogs, and that's usually because something has changed because they've obviously been born with the anomalous vessel and had it all their life, but often something's changed and.

They may well get an inflammatory disease, an infectious disease, or a concurrent disease that then suddenly, later in life causes them to present clinically with a portosystemic shunt. So often young animals, but don't exclude it in middle-aged or sometimes older dogs and cats. And many of these cats show signs of hepatic encephalopathy, which is this sort of neurophysiological disorder of the central nervous system, and we think it's predominantly related to ammonia, of course, and that's something we can measure.

Luckily, we don't see very often cases of acute hepatic encephalopathy. It's mainly chronic AG, which is You know, behavioural changes, vague signs, so lethargy and depression, anorexia. Some animals with hepatic encephalopathy can become hyper excitable, so it's not always sort of depression, but I think for me, these owners bring the young cat or dog in and you're expecting a lively kitten or puppy and, you know, don't, don't have that.

So, you know, depression is something I think we see quite, quite commonly. Yeah, pathogenesis of phatic encephalopathy. We don't completely understand it, but at least the, one of the main substances which is leading to patic encephalopathy is, is, is ammonia, but there's a whole bunch of other, compounds as well that can lead to hepatic encephalopathy.

And we also understand that inflammation is very important as well in changing the blood brain barrier per mobility to ammonia. So, that's why we always try and get on top of, of inflammation in these cases. And there is a grading system for clinical hepatic encephalopathy.

But as you can see, these are sort of based on the human grading system and it's very subjective, you know, in, in, in cats. Other things you might see there sometimes, but not always, poorly grown, stunted, smallest of the litter. A whole bunch of cats are reported to have copper coloured irises.

We don't really understand why, but quite common in cats with shunts. Yeah, they may have gastrointestinal signs, vomiting, diarrhoea, changes in appetences, weight loss. We don't commonly see PDPU like we might in dogs with shunts, and, some cats like this cat might have a urinary tract disease related to the presence of ammonium urate.

And other congenital abnormalities are sometimes seen. So I've seen a cat before that was cryptaled, it had retained sciduous teeth, it had umbilical hernia as well as the congenital cord systemic shunt. So the diagnosis just like in this, this cat we looked at, so thinking about doing blood work, particularly to identify mild, moderate increases in liver enzymes, and then on to imaging.

So yeah, you may see decreased serum urea, just like Phoebe had. It's in part thought to be reduced due to reduced hepatic synthesis. So these cats, like dogs with a poor systemic shunt, they actually have a.

Generally slightly smaller liver that's lost some of its functional mass and that's thought to be because they don't have as many patotrophic factors throwing flowing through their liver in in early life. So they've got sort of a functionally small liver. So that can be why you see things like low albumin, low, urea as well, whereas in Patients with inflammatory liver disease and things, because they don't get fibrosis and cirrhosis, you'll be unlikely to see reduced functional changes.

You may see low glucose, not commonly, elevated bile acids, like Phoebe heads, importance of a postprandial test. If you can measure ammonia, but it's only something you can measure in practise, it's very labile. Some might have.

An increase in ammonia, but many times when they're actually with us in the consulting room or in that clinic, ammonia can be normal. So finding a normal ammonia definitely doesn't rule out a poor systemic shunt bi bile acid stimulation test followed by diagnostic imaging are the are the best things to do. And they managed medically or, or surgically and Surgical management is is thought to be the the better management option for cats.

This is relatively old article now, but it's still quite a good, good review article if you're really interested in reading more about this, this disease, and maybe surgical management is a better option because of the difficulties we sometimes have medically managing cats, period. But the issue is that significant numbers of cats do get neurological signs in the sort of postoperative periods, and that can be relatively mild or it can be, you know, full-blown seizures and status, epilepticus, and seizures are reported in, you know, up to nearly 25% of scent of cats. Seizures, seizures occur generally within the first sort of, you know, 3 days of surgery, and so hence why we keep these, keep these cats in after the surgery.

And then some of those cats never seizure again. Some have got a, a lifelong history of seizures, which, to be honest, you can usually control with drugs. Just have to be a bit careful about the drugs you sometimes use, make sure they're not hepatotoxic.

What about medical management? Well, maybe show that used in, cats that have got milder signs, those where surgery is not possible. If you were to ever see an intrapatic shunt in a cat, then surgery can be very challenging, maybe an older cat, cat with comorbidities.

But medical management can work quite well, particularly if you're able to medicate that cat, and it's probably one of the key things. And we aim at trying to reduce the number of gut derived toxins, particularly ammonia, and we sort of hypothesise that ammonia is produced, in the gastrointestinal tract from bacteria that, you know, break down urea, so urea is producing bacteria, so we Try and reduce the numbers of those bacteria and give them less substrate, so we change diet as diet as well. But as I mentioned, the other really important thing that's come out of human and laboratory animal studies is that inflammation or inflammatory cytokines are very synergistic.

With ammonia, so they increase the permmobility of the blood brain barrier to ammonia. So it's pretty critical that we try and control inflammation, infectious processes, and cats and dogs with poor systemic shunts are increased risk of developing, particularly infectious diseases, and that's in part because of bacteria that are going straight from their GI tract into their systemic circulation. So diet is probably the key.

It's definitely the key in in dogs and probably the key in cats. And so, you know, one of the main things is that they should not have protein restriction, particularly important in cats, of course, they've got an obli high requirement for protein. But you should feed them normal or slightly increased amounts of protein, good quality, highly digestible protein, and split the food probably into several times per day.

Particularly important in cats and, and probably important, sorry, particularly important in dogs, probably important in cats to try and reduce the hit of protein and hence ammonia on their, gastrointestinal tract at once. We use lactulose as well, so this disaccharide that gets degraded to short-chain fatty acids in the colon that trap ammonia is ammonium ions and also cause a bit of osmotic diarrhoea, so reducing the time there's contents in the colon for urea splitting bacteria to act on. And standard sort of doses to allow the animal to produce sort of 2 to 3 soft stools per per day.

We often use antibiotics. I don't necessarily reach for them as a first line. I'll reach for diets, so a good quality, highly digestible diet, GI diet or other, several times per day along with lactulose.

But if those are not effective, or if you have a cat with very severe patetic encephalopathy, you could use concurrent, antibiotics. And probably using amoxicillin or if you need to potentiate the amoxicillin. People do reach for metronidazole, but as we said, it's quite challenging in many cats to medicate them with metronidazole.

So you're looking for antibiotics that are effective against those urease producing bacteria and not commonly in this country, but in the US at least, neomycin is commonly used, but I think for me amoxicillin, ampicillin all potenti amoxicillin. So yeah, summary just to finish off managing these cats support systemic shunt, definitely and importantly look for infectious inflammatory causes and treat those. So urine tract infections are quite common and and others and, you know, as that cat ages, dental disease and skin disease, etc.

Etc. Don't restrict protein, high quality, highly digestible, normal to slightly increased amounts of protein, but feed them frequently. Think about lactulose and then possibly antibiotics if they're not responding, very well, or they have very severe signs of hepatic encephalopathy.

So I hope that's useful. We discussed sort of three of the more frequently identified liver diseases within the UK lymphocytic cholangitis, neutrophilic cholangitis, and then, cats with portistemic shunts. So yeah, thanks for listening.

I look forward to seeing you at the next session.