We constantly get called in for a sonogram owing to simple non clinical liver enzyme elevations? you know the ubiquitous SAP of 500-800 and change, ALT of 250 and change? and we scan the liver and it may be a bit lumped up like this attached image (Image 1, video 1) but only mildly so. Do I Bx? Sure why not? Do I perform an FNA? Yeh, maybe for usually unrewarding results because coarse livers have structural disease and need a core bx for an adequate Dx usually. But if the liver is smooth and structurally uneventful then FNA may give some cursory information like predominant inflammatory cell type such as Lymphoplasmacytic inflammation (LP). Also we may want to assess for copper storage disease, see how the inflammatory cells are treating the hepatic infrastructure i.e. the portal triads?. If they destroy the portal triads then this may be a lymphoma vs. a lymphoplasmacytic (LP) hepatitis or antigen surveillance ?reactive hepatopathy?. But we need a core biopsy for this. But more times than not there are no significant sonographic changes with the liver enzyme chase or only minor ones (Image 2) and tough to merit sticking with a core bx and spending $400+ of the owner?s hard earned $ for something likely benign? again we are talking asymptomatic patients and benign sonographic changes. So what do I do with these? Well I reason a bit I call upon a few of the pillars in the field?. I.e. Twedt has shown spurious elevations in liver enzymes that come and go. But in the course of chronic hepatitis (CAH) the ALT spikes early and then diminishing over time until fibrosis, cirrhosis and portal hypertension/liver failure shows up with low cholesterol bun and albumin may all occur-disastrous end stage liver failure. The liver has spilled all its enzymes at this point in these CAH cases so the levels aren?t high any more and the plump liver has now become a raisin with ascites from portal hypertension (see attached Image 3). So if I see a coarse liver, ?of coarse,? I encourage a stick and preferably a core or at least an FNA if it’s a money case and maybe a rhodanine stain as this may show copper? not quantifiable copper but at least we know its there and may be secondary or primary?. This rhodanine issue is something to look hard at in the future as its a bit lumpy as far as diagnostics go?..may be valuable maybe not and an fna is very easy to grab and get a few more pieces of info such as predominant cell type in inflammatory disease?. But aside form this crash and burn grape to raisin scenario with CAH>fibrosis/cirrhosis> portal plumbing stasis & portal hypertension>ascites that a Dobie or Bedlington or other dogs +.- cats (vanishing bile duct syndrome for example)(Image 4) may have. BTW I had a new appreciation for Sharon Center at Cornell when I saw that dx of ?Vanishing bile duct syndrome? come across the histopath read on that cat, which is why I keep that old image in circulation. I thought that was one of the coolest diagnoses I had ever heard?. End stage liver aside, I am particularly interested in the ?antigen surveillance liver? or benign ?reactive hepatopathy?. If I stuck every one of these benign livers (Image 2) that I see daily I would be sticking at every stop on a 10-hospital day and burning a lot of client?s college savings funds in a pet that is non clinical and minimal to no structural disease on the sonogram. This benign reactive hepatopathy honestly I see 10 x as much as I see significant liver pathology on a daily basis. So how do we reason through these benign liver cases and try to do something for the pet and do the best by the owner of course diligently following the patient and LEs to ensure more significant disease is not ?emerging.? BTW key buzz term to a client ?emerging pathology.? You want to get them to follow-up use this term and watch their eyes light up?.. ?Hmmm, Fido might have ?emerging pathology? we had better keep an eye on him.:)? So lets call these benign livers ?reactive hepatopathy? (RH). But if a structurally normal looking liver with LE elevation on follow-up becomes more coarse with increased portal markings (thickened and brighter) and the liver is getting a bit ?lumped up?, then we need to core bx which is why a 4 week follow-up US is important especially if LEs are still elevated. (Videos 2 & 3). This also gives the owner time to process the reason for bx if reluctant during the initial conversation. So in the title I said ?Grandma? & The Liver Enzyme Chase–What do they have in common? What the heck is Lindquist talking about here? Well to name drop another pillar in this discussion is a quote from Willard: ?Liver enzymes are elevated more often from non hepatic disease than from hepatic disease.? This is what I mean by reactive hepatopathy (RH). So when you slice up a ton of histopath in liver, GI, pancreas in clinical and non clinical dogs and cats you will find a lot of LP inflammatory disease in all 3 organs. Clinical disease and histopathological disease are 2 different issues. Just search the sonopath archive and it keeps coming up and my personal archive is 20x the size of what?s online for members so you get my point here. How do we explain this phenomenon? Well my analogy of the body organs? dog, cat, you, me, Joe the plumber, a stinky adrenal ferret, a bearded dragon, it doesn?t matter we are essentially made up of an archipelago of organ systems/islands or essentially a family? the blood and lymph is the way they are all connected and there are things we family members keep to ourselves but when there are issues with us that are ?emerging? then actions or subtle communication may spill out (antigens). Then when one of us (an organ system) throws a tantrum everyone knows about it (systemic disease)! So which organ is ?grandma?? Of course ?grandma? is the liver because she has to deal with everything upstream coming down to her in the portal system. Here?s the modern ?organ family?: The GI is the ?center of attention? child in the family. The pancreas is the shy child that builds up stress and eventually throws a tantrum. The twin kidney brothers always do things together and dress the same way and you sometimes can’t tell one from the other. The adrenals are the low maintenance older brothers that are steady and ready to kick in when needed but may drop off the map and be unreliable in certain families (Addisons). Dad is the ?heart? of the household being a good provider (oxygen and exchange of nutrients) and causing household hypoxia of he starts to fail. Other members include the good aunt thyroid that gets old and cranky (hypothyroidism), grandpa full of wisdom (or not) is the brain, and mom is the skin that holds us all together. See its just one happy family that goes through ups and downs and internal fighting and quarrels and sometimes disasters. So when you think of it this way then you get a better idea of what that enzyme chase is all about for ?grandma?? I mean ?the liver?. When I was a kid my grandmother would sit in her chair at Easter, Christmas, or New years and all my cousins and 2 sisters (13 girls altogether) would one by one come to grandma with their issues usually having to do with other family members (organs) to grandma would take ?hit? after ?hit? from each of the household ?pathologies.? She could deal with them all fine because she was a ?liver?, a very resilient organ made to ?deal? with the body?s issues. But when my crass uncle Gail would get under her skin over the course of the day grandma would eventually get pushed over the edge (Liver failure) and she would have to adjourn to the kitchen for some ?treatment? making an apple pie or something (SAMe). My brother and I would be in the corner of the room watching the New Years day football game ?walled off? from the cousin insults with uncle Gail spitting out his crassness (sepsis) sitting next to us and grandma systematically would deal with his insults along with all the others, and somehow seemingly enjoy doing it. So you can see the body is essentially a ?modern day family?. Technically here is my thought process regarding liver assessment and the sonogram. No worries its not like I think of my cousins and grandma during a sonogram? If there is something ?off? upstream in the portal system like the spleen (splenic vein to portal vein) such as reactive ?hypersplenism-lymphoid hyperplasia? owing to some antigen stimulus like pancreatitis in cats or lyme disease in dogs, or if there is IBD or worse in the GI (mesenteric vv and gastric & pancreatoduodenal vein + other vv to portal), or maybe acute (less frequent) or chronic active pancreatitis (most frequent form in vet med dog or cat) or worse (pancreatoduodenal vein to portal), or any other insult that enters the portal system, then essentially grandma has to ?deal? (SAP, ALT +/- AST). Even systemic disease such as hypo or hyperthyroidism, passive congestion and liver hypoxia from right heart disease, systemic hypoxia from left sided congestive heart failure, azotemia from kidney disease when the ?twins? both get sick at the same time, or azotemia from Addison?s because the ?big brothers? haven’t been heard from for months? all these systemic diseases eventually get there to grandma and affect her in some way. Grandma Kupfer responds with a reactive spilling of SAP (congestion brush border enzyme) and ALT (cytosol enzyme) and if the insult is more significant then AST (mitochondrian enzyme) or GTT get involved. If grandma can?t deal with the household any more and her parenchyma is saturated or if her plumbing doesn’t work then bile acids and bilirubin are elevated. If interfamily communication has been compromised (hemolytic disease) then pre-hepatic hyperbilirubinemia may be the problem. Ok have you all cancelled your SonoPath membership now thinking that the founder has seriously lost his crackers? Maybe it was all those cases processed over the last 8 years?or just too many holidays with the extended family ?.who knows. But I fall back on what a great speaker in vet med once told me regarding speaking advice in, of all places, Fiumicino airport in Rome, Italy in a by-chance meeting before I spoke at ACVIM on the UGELAB procedure a few days later. Yes, I was a bit nervous as it was my first big time talk. He said ?no matter what or if you get in a pickle at the lectern, just tell them how you think.? Hence why I am producing this blog entry on liver assessment. Telling you how I think?..for what its worth?Scary isn?t it! So as wacked as it may seem this is how I think through these liver changes especially the liver enzyme ?chase? in non-clinical patients. I go looking for portal or systemic insults, I may FNA for more info, if the LE?s are climbing I may core bx and chase copper or other, or I may do this empirical protocol (listed below) especially with pet owners that don’t want a needle in their pet?s liver. Given that most of these antigen surveillance livers are LP infiltrates then I try to reduce antigenicity as these may be non-clinical IBD dogs and cats especially if I see chronic changes in the pancreas (coarse parenchymal markings and irregular capsule from scar retraction) and GI (increased muscularis/mucosal ratio, thickened submucosal layer, mucosal striations or speckling): Lindquist Antigen surveillance/reactive hepatopathy empirical tx: Fenbendazole if no recent worming Metronidazole for immune modulation +/- antiparassitic 14-21 days Clavamox for potential bacterial infection 14-21 days Actigall if the Gall bladder aspires to be a mucocele 8 weeks + Hypoallergenic diet with separate protein source than the patient has been ingesting historically SAMe if I want to get grandma some apple pie. Recheck LEs in 4 and 8 weeks. You will not need all of this just plug and play based on the presentation and patient. Then, let me know if it worked for you would love to do a study and it would be great if we at least had fna to support the LP phenomenon and not just empirically attempt to chase away the reactive enzymes. The common denominator in the success in these cases I surmise is likely the diet change but I can reason through doing all these measures in certain cases. I have seen many of these ALT issues resolve this way. In dogs, SAP usually is there to stay once its started in my experience. I just don’t like when it rises rapidly. Look for LSA Lipidosis, suppurative hepatitis, biliary disease/mucoceles/plugs and such when SAP jumps form 400 to 1400 in a couple of weeks in dogs. But once SAP is in town, no matter why its there (idiopathic thyroid, Cushings, the wind changing direction, whatever?) it may diminish here and there but its usually there to stay. Cats are different in that SAP is important in any cat and warrants an fna. CAVIAT: This empirical Tx for presumed antigen surveillance livers is NOT an approach to take with significant parenchymal disease as enzyme levels drop as the liver ?smokes? its parenchyma into a raisin with CAH so there is less enzyme to spill as the cells are replaced with fibrosis. These cases need core bx (Video 2), portal vein Doppler, copper staining, and aggressive treatment if treatable. So after all that what does the community do when faced with the liver enzyme chase?