Page 938 - Cote clinical veterinary advisor dogs and cats 4th

460 Hepatopathy, Copper-Associated, of Labrador Retrievers

HISTORY, CHIEF COMPLAINT Initial Database ○ Success results in histologic resolution of
• Subclinical Cu-AH Laboratory and imaging findings are similar to hepatitis; endpoint of therapy is sustained
VetBooks.ir (e.g., preanesthesia lab testing or geriatric tory hepatitis (pp. 174, 442, and 452). ○ Duration of chelation treatment varies;
those of any acute or chronic necroinflamma-
○ ALT elevation discovered inadvertently
normalization of ALT.
pre-treatment hepatic Cu concentration
panel)
Advanced or Confirmatory Testing
○ ALT may be normal in subclinically
affected dogs; it is a poor biomarker (low • Liver biopsy: laparoscopy (preferred [p. often correlates with the duration of
therapy (higher concentration, longer
sensitivity) for Cu accumulation. 1128]), laparotomy, or ultrasound guided treatment).
• Acute Cu-AH: signs due to hepatocellular ○ Ideally from ≥ 3 lobes (heterogenous ○ Repeated biopsy and Cu quantitation is
necrosis; chief complaints: disease), deeper and more surface oriented helpful for clinical decision making.
○ Can be mild to severe and develop over ○ Regenerative nodules may contain decep- ○ Although it interferes with Cu uptake
a few hours to days tively low Cu levels and should not be by enterocytes, zinc is not effective for
○ Can include weakness, lethargy, vomit- submitted for quantification. de-coppering the liver.
ing, diarrhea, anorexia, variable jaundice, • Histopathologic findings vary in severity of • Transient dosing of prednisolone may aid
coagulopathies, hemolysis (rare), collapse hepatocellular necrosis and often are worse in reducing hepatitis and improving patient
○ Hepatic encephalopathy (p. 440) in zone 3. Necroinflammatory response and well-being and appetite. However, negative
• Chronic Cu-AH: can include lobular collapse are followed by bridging concerns include potential of vacuolar
○ History of past episodes of ALT elevations fibrosis. hepatocellular swelling in a collapsed or
or unexplained illnesses • A panel of stains is superior for assessment. regenerative nodule surrounded by fibrosis
○ Slowly progressive or periods of lethargy, ○ Hematoxylin-eosin (H&E) for general with increased cholestassis.
anorexia, vomiting, weight loss, diarrhea, assessment • Supplement pyridoxine (vitamin B 6 ) because
polydipsia/polyuria ○ Reticulin stain for lobular collapse D-penicillamine increases requirement for
○ Ascites ○ Masson’s trichrome or Sirius red stain to vitamin B 6 .
○ Hepatic encephalopathy highlight fibrosis • Chronic after Cu removal
○ Rhodanine or rubeanic acid for Cu ○ Taper D-penicillamine by 50%, then every
PHYSICAL EXAM FINDINGS staining other day, and finally discontinue
• Subclinical Cu-AH: no abnormal findings • Quantitative Cu concentration often cor- ○ Lifelong restriction of Cu intake
• Acute Cu-AH: weakness, variable jaundice, relates with clinical severity. ○ No benefit has been shown for providing
pallor, abdominal discomfort, ecchymoses ○ Atomic absorption spectroscopy is most zinc supplementation to Labradors eating
• Chronic Cu-AH: poor body condition, common test for quantitative Cu only low-Cu diet.
unkempt appearance, variable jaundice, ○ Digital Cu quantification (DCQ) by • Trientine hydrochloride 5-7 mg/kg PO q
abdominal effusion, bleeding computer processing of rhodanine-stained 12h, an alternative Cu chelator, can be given
tissue correlates with the more common if D-penicillamine is not tolerated (although
Etiology and Pathophysiology atomic absorption spectroscopy, provid- it is very expensive).
• Risk increases with concentration of dietary Cu ing an alternative method, and has the Antioxidants:
and the pattern of gene mutation. It is thought advantage of assessing multiple biopsies • D-alpha-tocopherol (vitamin E 10 U/kg PO
that elevated Cu concentration increases oxida- of different regions. q 24h)
tive injury from other triggering events. These ○ Affected dogs usually have values • S-adenosylmethionine (SAMe 20 mg/kg PO
reactions induce hepatocellular death. > 1000 mcg/g (mcg/g = ppm) dry weight q 12-24h; give q 12h until the patient seems
• Eventual lobular collapse occurs predomi- liver (DWL), but normal is less than stable)
nantly in zone 3. The ensuing necroinflam- 400 mcg/g. Markedly affected dogs can Hepatoprotectants:
matory response stimulates fibrosis. Different exceed 2000-3000 mcg/g. • Ursodeoxycholic acid 15 mg/kg PO/day:
lobules and regions of liver lobes may in cases with significant necroinflammatory
accumulate Cu at different rates and undergo TREATMENT changes, notable suspected/proven fibrosis,
varying degrees of necrosis so that severity and/or subsequent reduced hepatocellular
of focal damage varies within the liver. Treatment Overview function or cholestasis
• This process allows for temporal ups and downs • Reduce Cu intake: food, supplements, • Silibinin (silybin): no proven benefit but
in serum ALT activities, clinical findings, as potentially water sources safe; commercial preparation available in
well as variable severity of biopsy findings. • Chelation therapy to help reduce hepatocel- combination with SAMe (Denamarin)
lular Cu and increase elimination Supportive care: see Chronic Hepatitis chapter
DIAGNOSIS • Antioxidants to reduce oxidative stress/ (p. 452)
reactions within hepatocytes
Diagnostic Overview Nutrition/Diet
Labrador retrievers with serum ALT elevations Acute General Treatment • Prescription diets for liver disease are low
are logical suspects for Cu-AH. Confirmation • Acute hepatic necrosis treatment (p. 442) in Cu and should be fed during and after
depends on histopathology from liver biopsies • Chelation therapy as soon as possible chelation therapy. These diets generally
showing zone 3–predominant hepatocellular contain 3.5-7 ppm dry matter basis of Cu.
necrosis, positive Cu staining, and abnormal Chronic Treatment • In one study, hepatic Cu could be normalized
quantitative Cu concentrations. Chelation: in 50% of subclinically affected dogs with
• D-penicillamine 10-15 mg/kg PO q 12h diet alone.
Differential Diagnosis chelates Cu, promotes urinary Cu excre-
• Chronic hepatitis (inflammatory, immune tion, and provides other protective effects Drug Interactions
mediated, infectious) by binding of the Cu from oxidative Oral zinc can impair chelation therapy.
• Acute hepatic injury (hepatotoxic, infectious, reactions.
other) ○ Initiate use if in affected patient hepatic Recommended Monitoring
• Hepatic neoplasia Cu is > 500 mcg/g per DWL • At 7-14 days after starting chelation and
• Pancreatitis ○ Administer 1 hour before feeding to reduce again in 3-4 weeks: include physical exam,
• Bile duct obstruction or rupture nausea and vomiting, which is common. CBC, serum chemistry profile, and urinalysis.

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