What is current thinking in Cocker Spaniel chronic hepatitis?

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Penny Watson — Fri, 09 Feb 2024 14:34:44 GMT

Difficult to know then whether the cyclosporin is doing anything or not. Also difficult to know whether you should be chelating this dog as well because of the originally high copper. A repeat biopsy would help you but difficult to justify with the lack of clinical signs. I would certainly take the copper seriously and double check it is still on the hepatic diet. You could try weaning off the cyclavance and see if the ALT goes up? If it stays the same, it is likely not doing anything and not worth the time, expense and risk of long term side effects

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Thu, 08 Feb 2024 17:22:47 GMT

ALT has remained similar to what was 5 months ago (i.e. down on what had been before that). still on 75mg ciclosporin once daily (cyclavance - getting harder to get...) and liver diet.

Remains conlincally well (other than arthritis).

ALT (VS2, previously done on VetTest): 486 U/L (10-118)

ALKP (VS2, previously done on VetTest): 304 U/L (20-150)

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Thu, 04 Jan 2024 20:06:24 GMT

Only that was stiff before Xmas and got a librella injection - haven't seen back myself.

I'll try to get ALT and ALKP repeated if I can. Still on ciclosporin, not sure re nutramarin if continued or not, think hepatic diet has continued.

Still clinically well (other than the arthritis).

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Sarah Keir — Thu, 04 Jan 2024 18:00:03 GMT

Hi Beats, Any update on this case?

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Alasdair Hotston Moore — Sun, 10 Sep 2023 13:31:13 GMT

Thank you Penny

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Sun, 10 Sep 2023 09:27:11 GMT

Thanks. Is on royal canin hepatic. Will see what alt is in couple of months. Thi

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Penny Watson — Sun, 10 Sep 2023 07:55:30 GMT

The response to the cyclosporin sounds encouraging. Is the dog also on a low copper diet? I am even more convinced the copper was significant in your dog because with a normal bilirubin it isn't going to be 'secondary to cholestasis'. A low copper diet would be a good start and you could consider chelation in a couple of months if the ALT stays significantly elevated

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Sat, 09 Sep 2023 08:47:06 GMT

Thanks Penny!

Bilirubin was not elevated.

Have continued the diet and s-adenosyl-methionine.

the quantitative was half of a biopsy, the other half going to pathologists and all pathologist biopsies were reported as similar, however there were some regenerative nodules and it is possible that the half that went for quantitative was different from the half that went to pathologist. Method was whatever is done at lab in USA where VPG send them on to - I'm pretty sure was dry weight based.

The ALT did not reduce with the pred.

After 6 weeks on ciclosporin once daily (with no GI signs) ALT down to 441 and ALKP is 497.

Going to continue ciclosporin once daily on that basis and probably check again in couple of months.

Dog continues to have no clinical signs.

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Penny Watson — Sun, 09 Jul 2023 15:22:37 GMT

Hi Beats (??) Glad to join this discussion - only just changed my Vet surgeon settings to get weekly updates of all discussions, not just Samsoc and clearly an area I am interested in! I agree with all the previous comments (except metronidazole which I haven't found to be particularly helpful - even in young dogs with congenital shunts where I prefer ampicillin- and your dog is unlikely to have HE unless he has other evidence of portal hypertension). A comment on the copper - it does sound as if there was a lot on histology (3/5) and this won't be "secondary to cholestasis' (as often reported by pathologists) unless your dog is significantly cholestatic - ie was bilirubin elevated? If not, it is likely significant (and even if he was cholestatic, it is likely still significant) so certainly continue the diet, use anti-oxidants and consider chelation longer term. The low quantitative may be because you always send off another piece of liver to that the pathologists looked at so may have sent a fibrotic bit or a bit with regenerative nodules which tend to have lower copper. What method did the lab use? If they used wet weight measurements these are unreliable - you should have dry weight atomic absorption spectrometry - we haven't found anywhere in the UK who will do that for us and now send samples to Colorado. For the immunosuppression: in n=1 I have had great success in a cocker with similar histology to yours (but without the copper) both in reduction of clinical signs (which yours hasn't got!) and reduction in ALT. I chose to use it first because the dog had a lot of fibrosis on histology and I was worried about developing portal hypertension, Did the pred reduce the ALT in your dog? The clinical signs triggered might suggest the dog has incipient portal hypertension which the pred would destabilise, Not aware of anyone using omeprazole with cyclosporine and I would avoid this in a dog with liver disease as you don't actually want to increase the ciclosporin dose any more than already with risk of liver toxicity

PS to join the other thread - blue green algal supplements seem to be popular as well in humans....honestly, google them....clearly not good for the liver either

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Thu, 06 Jul 2023 18:44:43 GMT

[quote userid="16471" url="~/f/clinical-questions/30683/what-is-current-thinking-in-cocker-spaniel-chronic-hepatitis/241908#241908"]

Must admit I hadn't heard about the omeprazole theory. The only research I could find just now suggests not much effect (in people).

https://pubmed.ncbi.nlm.nih.gov/8443034/

Would be interested to know more

[/quote]

Sounds like I dreamed it up! Could have sworn I read that on VetSurgeon once upon a time, but searched just now and hit a blank. Must have been someone verbally suggested it on some occasion to me.

All I found when googled was this:
https://todaysveterinarypractice.com/wp-content/uploads/sites/4/2016/06/T1501C13.pdf

(and is very irritating searching for a drug with different spellings)

I guess, of drugs on that list in table 1, while erythromycin or ketoconazole might increase serum ciclosporin levels more convincingly, it's frowned upon to use antimicrobials like that. And grapefruit juice isn't very palatable.

Sounds like giving omeprazole alongside ciclosporin makes no difference though (I think it would be well known if it did given the price of an omeprazole capsule!)

I make it £63 a month if giving 5mg/kg once daily for a 15kg dog, i.e. 75mg (0.75ml) once daily (and gets 50ml cyclavance from VetUK), so that would be sustainable in this case. My concern is if I end up doubling that it would not be. But seems reasonable to try at that dose and see if works.

Thanks!

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Roger Wilkinson — Thu, 06 Jul 2023 17:16:00 GMT

There was a big dose range of CsA in that paper. I usually choose a dose depending somewhat on severity of illness in each patient (lower if less severe) and work upwards. If this one is asymptomatic then I agree it would be reasonable to start low end. 5mg/kg Sid po sounds fine.

Must admit I hadn't heard about the omeprazole theory. The only research I could find just now suggests not much effect (in people).

https://pubmed.ncbi.nlm.nih.gov/8443034/

Would be interested to know more

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Thu, 06 Jul 2023 16:43:03 GMT

Thanks Roger, I've read that article and wasn't totally sure on what starting dose of ciclosporin to try (5mg/kg q12hrs?). Also do you start on once daily and then increase to twice daily after a copule of weeks if tummy OK? Could afford 5mg/kg once daily I think..., but even that is pushing it, so not sure that going higher if needed will be an option.

Dog has no clinical signs (or at least didn't have anything the matter until I started it on preds!), I don't want to make it ill with ciclosporin now also!

Finally, do folks still give with omeprazole with idea of getting more of the ciclosporin through the stomach and needing less dosed then given the cost of it, or is that out-dated?

Really appreciate you chiming in, Roger!

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Roger Wilkinson — Thu, 06 Jul 2023 15:09:40 GMT

onlinelibrary.wiley.com/.../jvim.15591

That article was a game changer. Previously the rationale for immunosuppression was weakly evidenced: there being no prospective studies.

And even though there was some evidence of response to steroids, many cases still have disappointing outcomes.

With CsA, 80% of cases achieving remission (our experience mirrors this) means it's got to be treatment of choice I think. I've found it really amazing that even dogs with marked hyporexia, ascites and portal hypertension will still respond.

All the best

Roger

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Richard Carter — Thu, 29 Jun 2023 17:04:46 GMT

I know it’s no longer politically correct but I really like metronidazole at 10 mg/kg sid on relapsing hepatitis/ pancreatitis- essentially the rationale being reducing ammonia and assisting RE system if liver function compromised either with disease or fatty changes. It’s kept many from relapsing to point of needing hospitalisation

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Richard Carter — Thu, 29 Jun 2023 16:58:31 GMT

St. John’s wort is very popular and very poisonous

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Alasdair Hotston Moore — Thu, 29 Jun 2023 07:36:06 GMT

Can you update your profile so we know who you are! This makes all our contributions more valuable

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Wed, 28 Jun 2023 19:59:25 GMT

so on 1mg/kg daily (15mg preds) was unmanageably PUPD, reduced to 10mg/day (0.67mg/kg), but was in today V+. Was apparently clinically healthy prior to preds, so can't help but feel I'm not helping here. still plan to give one more week and then recehck ALT most likely.

Cu staining showed intracytoplasmic hepatocellular staining in groups of hepatocytes throughout the lobule, but most prominent periportally (score 3/5). But then the tissue Cu was not dramatic: 478ppm. Think will jsut continue on RCW Hepatic food with added chicken based on this, and not consider chelation therapy with d-penicillamine.

Might try ciclosporin if pred side effects are not good is my only other thought really.

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Gillian Mostyn — Thu, 22 Jun 2023 09:30:40 GMT

[quote userid="2675" url="~/f/clinical-questions/30683/what-is-current-thinking-in-cocker-spaniel-chronic-hepatitis/241702#241702"]Interesting they say up to 18% of human hepatic [/quote]

I was also surprised at this! To be fair, it says 18% of drug-induced liver injury, not all liver injury, but that must still be a hell of a lot of cases!

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Beats — Tue, 13 Jun 2023 13:13:10 GMT

That consensus paper link was brilliant, Sarah, just what I was looking for - thanks!

It does seem to have high copper also on staining, especially peri-portally. I've requested copper quantification.

Will probably keep on the RCW Hepatic diet (+ extra chicken) that had been placed on then. I'm not sure that the cost of the penicillamine for 6 months will be viable unless there is a cheaper source somewhere I haven't found yet.

Still thinking of giving 2 weeks on 1mg/kg pred and rechecking ALT at this stage. Might consider ciclosporin also, but again cost...

The dog is clinically well presently, so I'm reluctant to make unwell at present time with treatments potentially. Difficult balancing act.

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Richard Carter — Sat, 10 Jun 2023 06:02:49 GMT

Interesting they say up to 18% of human hepatic caused by herbal and dietary supplements!! You never see that in the advert
Also the increase in Cu related diseases following changes to dog foods in the 1980’s

Also the recommended rx of dexamethazone over pred if ascites present to avoid mineralocorticoid effect

Slightly over 50% complete or partial remission on pred rx

RE: What is current thinking in Cocker Spaniel chronic hepatitis?

Sarah Keir — Thu, 08 Jun 2023 17:12:56 GMT

Penny Watson at Cambridge is the person to speak to about liver disease.

There is relatively recently published consensus guidelines for chronic hepatitis - https://onlinelibrary.wiley.com/doi/10.1111/jvim.15467 free access

High copper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272033/O ) and even lead (https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.16149 ) are now recognised to be very common and important in canine hepatitis