Cat has acute episodes of extreme ALT levels. Vet and we are at a loss as there's no obvious toxin access, looking for weird or uncommon ideas

Question

We've been to a pretty good vet. We know the symptoms, but we just can't figure out what might be going on, or a cause. The vet says its serious and possibly life threatening, but he's at a loss what else it might be as well. I'll write what we know - any ideas, insights, suggestions for uncommon causes, weird or exceptional toxins, ideas sparked by the information, or anything else, would be helpful, to prevent recurrence.

The cat is about 10 years old, spayed female rescue, lived with us 5+ years, 5kg, rude good health apart from occasional bouts of stress cystitis (urinary stress diet + extra soup/water + cistaid given to counter this). Also pathologically misanthropic - her general view on humans is that apart from opening doors and providing food, they should all go away. But we love her anyway :)

First episode & vet visit

About 2 months ago (25 April 2018) she had an acute episode of some kind of poisoning. She vomited a lot, but otherwise seemed fine all day. The next morning, over the course of 12 hours she went from "off her food" in the morning, to pretty much laid down and indifferent to everything waiting to die by afternoon, to the point of not even hissing, avoiding or clawing at human fingers near her face. Serious stuff for her.

We contacted the emergency vet hospital, who gave us some tips, and did some online research, and watched her a long time. She had no confusion, when pushed off the bed she didn't fail in co-ordination, no dilated pupils, tongue was very pale though.

We took her to the vet (well known to us, and competent). They identified a significant heart murmur (usual feline myopathy) in passing, did ultrasound and bloods, which confirmed no liver tumour or masses, no sign of internal bleeding, but general signs of gross insult/damage to the liver, some anaemia (25 on whatever scale is used in the UK) and off the scale for ALT (Alanine aminotransferase, an enzyme related to liver cell necrosis/toxicity: the level was 6000+ according to independent lab they asked to retest it. I gather usual is < 100 ish?). She was so gone that the vet could take a blood sample from the neck without protest or sedation (when she recovered next week, the same vet couldn't even palpitate her stomach without risk of injury!). The conclusion was liver toxicity, and indeed the next afternoon she noticeably regained her appetite, and suddenly began to recover, and the episode ended. She was put onto beta blockers and thinners (Atenolol + Plavix) for the heart condition, and tolerated them, and all was well. A retest a week later showed ALT level had dropped to ~ 600 and the anaemia had "resolved".

Today's episode & vet visit

This morning (2 June 2018) she was off her food. There hadn't been any vomiting, but she remained off food all day and by 4pm was once more showing the same signs as before - laid down, lethargic, and so on. We decided the risk was too great to leave overnight, and took her to the vet.

We arrived at 7pm, and he said at once it was serious and probably life-threatening. He expressed concern it might be internal haemorrhaging or a missed tumour, and redid the ultrasound, but there's no evidence of leakage or pooled liquid or other issues internally, and no masses in the liver or anywhere else he checked. Yet again ALT levels are sky-high - his machine goes up to 2000 and ALT is off the scale (he said done by a lab it could easily be 6000 or whatever), and anaemia is lower than last time, just 18 now, and the tongue is very pale. Most other levels are normal-ish, I gather. He didn't want to use a drip to address blood pressure as that would accentuate the anaemia issues, and said to stop giving the blood thinner until we know more, as well. We finally left about 9pm. In all, he saw her for almost 2 hours, compared to the usual 10-15 minute consultation.

We went through a bunch of possibilities but he said that the symptoms looks most like paracetamol poisoning - but that it doesn't fit that either. It could be an infection, except there's no other evidence and why would it go then return? It seems most likely she ate something - just inhaling even dust from a tablet wouldn't be enough, she would need to eat quite a lot to have this effect, and there just aren't any tablets around, and in 5 years we've never seen her scouring the floor for anything. She's in a flat (apartment) so she's isolated from any other cats and probably all/most pathogens they could carry. She has access to a terrace with some plants, but this doesn't resemble any plant poisoning he could suggest. The household products used aren't normally spilt, and those we do use he said would cause irritation, diahrrea, or vomiting, which we didn't see this time.

And.....

We're at a loss, and so is the vet. I'm staying up all night to watch her breathing, in case it worsens and she suddenly needs to go to the emergency hospital. I'm about 60/40 that she will be OK, but the fact it's happened twice and we can't think how, even after taking all the precautions we can think of against odd eventualities, is really a worry.

Like I said at the start - any thoughts, insights, suggestions or things missed, that this narrative sparks off, or that might be worth checking or considering, would be very welcome.

Updated information

Below are the actual lab/test results, maybe they help suggest ideas. I've highlighted anything marked as outside "normal" ranges. All units are metric (we're in the UK).

• First visit (25 April, weight 5kg): heart 190, total protein 58, alb 26, glob 32, A:G 0.8, Na 144, K 4.2, Na:K 34, Urea high 16.4, creat 146, ALT high 6462, alk phos 21, total bilirub 9, gluc high 7.2; red cells low 4.2, Hb low 6.3, Hcrit low 22%, MVC 52.3, MCH 15, MCHC low 28.6, Retic'cytes 55, platelets low 17, white cells 8.3, neutrophils 4.1, lymphoc 3, monocytes high 1.2, eosinoph 0, basoph 0.
  Urine normal: LEU+NIT+KET+BIL+BLD (blood?)+GLU (glucose?) all negative, UBG/URO normal, Pro(tein?) +, pH 7.5, SG 1.005, refractometer s.g. 1.040, JG.
  Lab additional comments: occasional reactive lymphocytes, occasional neutrophils have small dohle bodies, mild anisocytosis, occasional/mild polychromasia, mild echinocytosis, occasional Heinz, rare metarubicytes, occasional macroplatelets, minimum manually estimated platelet count 30, quality EDTA good, RBC agglutination RT neg @ 1.5 dilution, no azotemia, in saline agglutination included. Possible options include (for ALT): liver disease/trauma/neoplasia, (for anaemia) possible chronic disease? CBC: thrombocytopenia, anaemia - mild regeneration.

• Followup to first visit (1 May, sedation): cardiac: HCM diagnosed. 3/6 gallop, thickening/enlargement, no thrombus though. Liver scan: no masses or cystic lesions, heterogynous echogenicity throughout, granular appearance. Options: diffuse inflammatory reaction? toxicity? infection? ALT down to 600s, anaemia resolved. Options: likely toxicity? Heart meds begun: Atenolol 6mg, Plavix 19mg, both in the form of 1/4 of a tablet once daily

• Second visit (12 June, printout hard to read some letters, sorry for any typos): ALB 31, ALP 13, ALT high [off scale] >2000, AMY 365, TBIL 5, BUN high 11.2, Ca 2.1, Phos low 0.82, CRE high 192, gluc high 12.1, Na low 137, K 5, TP low 52, Glob 22, QC (quality?) OK, HEM 0, LIP 0, ICT 0, Hcrit low 18.5%, HGB low 5.6, MCHC borderline low 30.3, WBC 14.2, ?GRANS 11.7, %GRANS 82%, L/M 2.5, %L/M 18%, platelets "extremely low" 15, retics 2.7%. v pale mm, heart 200, very (vv) weak pulse, no respiratory distress, well hydrated, no free fluid in abdomen/chest, liver darker than normal/granular pattern, signs of regen(eration?) with reticulocytes, no reaction to jugular blood, concerned re depressed appearance. Plavix on hold due to anaemia.

Answer 1

Given the information in your question – and I haven't evaluated the cat or seen the full lab work or diagnostics – I am less inclined to think this is an acute hepatopathy as would be caused by toxin ingestion. The repeated episodes point towards more of a chronic condition, and I would be concerned that there may be an underlying cancerous process.

The anaemia in itself is in my view more immediately concerning than the ALT elevation. I hesitate to speculate on the cause of the anaemia without more information, but it seems this is likely one of those anaemia of chronic or inflammatory disease that is hard to pinpoint. It could be due to inflammation in the liver, cancer, and any number of other causes. Blood loss seems fairly unlikely given the normal ultrasound. Was a reticulocyte count run to assess whether it is a regenerative anaemia, to help rule out causes? Or better yet was a blood smear done? A hematocrit of 18% is getting to a point that is quite concerning; if it gets to 15% then a blood transfusion has to be considered.

My assumption is that all the other liver enzymes are normal, with no evidence of cholestasis (elevated Alk Phos, elevated bilirubin, etc)? With only ALT so elevated, there is certainly hepatocellular injury occuring, but the cause is more challenging to say.

ALT can come from other sources, such as red blood cell destruction, muscle disease, etc, however given the degree of elevation it is unlikely to be anything other than hepatocellular injury.

The fact that you have no identified tumour on ultrasound is good, but does not rule out cancer. Cancers can hide, they can be disemminated throughout tissue, there could be metastatic cancer from another organ which has not yet formed tumors visible on ultrasound. Lymphoma can look strange, and show up in strange ways.

Other possible causes are a flare up of cholangiohepatitis (usually not just ALT, but possible), or pancreatitis. The latter would sometimes show up on ultrasound, and can cause surprisingly severe ALT elevations. Then there are the causes of infectious hepatitis, which are more challenging to test since there are many. Outdoor cats are more likely to pick up these sorts of infections, but they don't have to go outside to the get them. With this sort of liver disease the infection that comes to mind is toxoplasmosis. Your vet could run toxoplasmosis titres if wanting to rule this out.

For the liver I would recommend sampling. This is not usually indicated in acute toxic episodes, but I am concerned that there could be something more chronic occuring here. The liver can be aspirated with a needle under ultrasound guidance. This is useful to assess for things like lymphoma, which may not appear as a discrete tumour. There is a risk of bleeding, which is always of concern especially in an anaemic cat. I would usually give a vitamin K injection prior to this type of sampling to minimize this risk. Really the best way to sample the liver is by exploratory laparotomy (abdominal surgery), but your cat is not presently a good candidate with the anaemia. It would however allow full evaluation of the liver and to take large samples of the liver, and other tissues if needed.

Best of luck with your cat, I hope you find an answer soon. Please keep us updated.