Question Details
Copper Storage Disease And GI Signs In A 4yr Corgi
by lrf9187 - April 17, 2024
Hi Steve!

I have a 4yr Corgi with chronically elevated liver enzymes and intermittent anorexia and vomiting (yellow/bilious, no blood or mucus). Does not get diarrhea. Parents moved to US from Poland in late 2023. An abdominal ultrasound in Poland June 2023 was normal. Blood work with me 11/2023 showed ALT 543 (high), AST 83 (high), Phos 2.4 (low), normal bilirubin and ALP. Normal PT/PTT. Liver values had improved previously on liver supplements. At this time (11/2023) while she had GI signs, her tongue was pale pink and pulse was weak, mid-depth, thin. She has significant dental disease with gingivitis. Overconditioned (BCS 7/9).

On a fresh food diet (Ollie initially, but I've since changed her to Just Food For Dog's cod-based liver diet since it's low copper).

Liver biopsy (wedge):
Examined were two sections of liver made from one submitted liver wedge biopsy. Around some central veins were lymphocytes, plasma cells and a few neutrophils, that only rarely extended into the hepatic parenchyma. Significant hepatocyte necrosis was not observed.
There were rare random lobular microgranulomas. Some portal triads had increased profiles of arterioles but portal veins were not diminished in the sections examined. There was diffuse mild hepatocellular vacuolation of glycogen like type.

SUPERLIVER PANEL:
A panel of histochemical stains (Masson's trichrome for fibrosis; Reticulin for scaffold matrix; Rhodanine for copper and Perl's for iron) was applied to assess and to better characterize liver architecture and heavy metal content. The results are as follows:
Trichrome, Fibrosis - There was no significant fibrosis. STAGE 0
Reticulin, Scaffolding - The reticulin scaffolding was unremarkable.
No parenchymal collapse, no parenchymal extinction and no nodular regeneration was identified.
Rhodanine, Copper - Nearly all centrilobular hepatocytes contained scant to small amounts of copper. This corresponds to a grade 2-3 out of 5 on a scale where grade 0 indicates no stainable copper and grade 5 corresponds to panlobular copper. Typically grades of 0,1 and 2 do not indicate pathologic copper accumulation and grades of 3,4 and 5 do indicate pathologic copper accumulation.

Perl's, Iron - There were low numbers of iron laden macrophages around central veins and in microgranulomas.


COPPER STORAGE DISEASE: results= 1890 ppm(dw)
Dry weight analysis of copper concentrations in canine liver tissue:
Deficient: <80 ppm
Normal: 120-400 ppm
Toxic: >1,500 ppm


***************** ADDENDUM COMMENTS - 12/18/2023
I reviewed analytic copper levels which were greater than 1000 ug/g DW liver. This would suggest that this animal would benefit from copper elimination therapy and dietary copper restriction. As mentioned, necroinflammatory changes were minimal to mild and there was no significant fibrosis suggesting this is early copper associated hepatopathy and a good prognosis is expected.

Liver pathologist that I spoke to suspected there might be underlying GI disease in addition to copper storage disease and possibly Portal hypoperfusion or mild Microvascular dysplasia. She recommended chelation with D-penacillamine for any dog with copper over 800.

In addition to the low copper diet change, I started her on antioxidants, pre-/probiotics, RX Vitamin's Hepatosupport, D-penacillamine (130mg daily) chelation, and Xiao Yao San.

One month later (it took a while to sort everything out), she's doing really well clinically, and her blood work looks great (ALT 44, AST 22, TBili 0.2, ALP still normal, Phos now normal at 2.9). The hepatic pathologist recommended that I keep her on D-penacillamine for at least 9 months total even though her ALT is now normal because of how high her copper levels were, but that I might be able to start weaning it at about the 6 month mark.

So my question: Given the potential sulfonamide side effects, I'm wondering if I could try reducing weaning the d-penacillamine faster than this in the hopes that Xiao Yao San is potentiating the effects and healing. Any thoughts or experience with this? Are the herbs, antioxidants and diet potentially enough on their own?
Replies
by naturevet
April 27, 2024
Lisa, what a great case. You've assessed and done everything perfectly! Well done!

Most overt copper storage disease seems to be characterized by Shao Yang disharmony. This dog presented with classic Liver Blood deficiency (causing a Wood Earth disharmony). I would bet a lot of the improvements are due to Xiao Yao San. The arteriolar dilation, lymphocytic plasmacytic cell population and the microgranulomas smack of endothelial dysfunction and likely secondary microvascular dysplasia, which you have addressed with Xiao Yao San. The fall aggravation is also classic for Liver Blood deficiency.

Since everything points as much to that as the primary pathology as to copper storage disease, I would guess you'd be able to wean off the chelation much faster. I'd be tempted to start finding the lowest required dose of penicillamine even now. My guess is that if you continue the herbs, diet and supplements, the liver enzymes will stay tamed

If you do go in that direction, please let us know how things go. Meanwhile, thank you so much for sharing your inspiring case!

Steve
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