Guide to copper-associated liver disease

Not advice, just good questions. Each one comes from an entry in this guide, so you can read the source behind it.

1. 1

   Was my dog's liver copper measured on a biopsy, and what was the number?

   A biopsy with a copper measurement is how it is diagnosed. Above about 1000 micrograms per gram of dry liver is typical, and 600 to 1000 is a gray zone.

   From: How copper-associated hepatitis is diagnosed

2. 2

   How will we know the treatment is working: ALT alone, or a repeat copper measurement?

   A normal ALT is a stand-in for success, but it can miss mild leftover copper. Repeat measurement is described as the best check.

   From: Monitoring treatment response: ALT and repeat copper measurement

3. 3

   Which side effects of the copper-binding drug should we watch for, and what do we do if he vomits after a dose?

   Nausea, vomiting and reduced appetite are the common side effects, and the statement lists ways to ease them.

   From: D-penicillamine: dosing, maintenance and side effects

4. 4

   Is anything we give, including supplements, getting in the way of treatment?

   Zinc is not used together with penicillamine, so any supplement is worth checking with the vet.

   From: Copper-restricted diet for life, and zinc as maintenance

5. 5

   What copper-restricted diet is right for him, and who will tailor it?

   A copper-restricted diet is advised for life, and a veterinary nutritionist tailors the plan to the individual dog.

   From: Copper-restricted diet for life, and zinc as maintenance

6. 6

   How much copper could our drinking water add, and should we do anything about it?

   The statement advises limiting copper in drinking water and suggests flushing copper pipes for a few minutes.

   From: Copper-restricted diet for life, and zinc as maintenance

7. 7

   Have other causes of the raised liver enzymes been looked for before any immune-suppressing drug is started?

   The statement advises a careful search for an underlying cause, such as copper, first.

   From: Immune-suppressing drugs in chronic hepatitis

8. 8

   How long will he be on each medication, and how will we decide when to lower or stop it?

   One practice article describes penicillamine as usually lasting six to nine months with a copper-restricted diet. Your dog's course may differ.

   From: Copper hepatopathy in dogs: a practical overview

9. 9

   If pancreatitis is part of the picture, how do the two conditions affect each other, and which signs mean call right away?

   Pancreatitis can block the bile duct, and recovery can be slow. A dog can seem better while the blockage still shows in blood tests.

   From: When pancreatitis blocks the bile duct: what 46 dogs showed

• Copper hepatopathy in dogs: a practical overview

  A veterinary practice article by Tinoco-Najera and Lidbury (updated February 2023). It says copper accumulation comes from an inherited defect in how the liver handles copper, from too much copper in the diet, or both, and can occur in any breed or mixed breed. Biopsy with special copper stains is the only way to diagnose it. It gives normal liver copper as under 400 mg per kg dry weight and abnormal as over 600. Penicillamine is the usual chelator, typically for six to nine months, with a copper-restricted diet. It notes zinc takes at least three months to work and that its effectiveness is questionable. Progress is followed by ALT or repeat copper measurement.

  • Biopsy with copper stains is the only way to diagnose
  • Can occur in any breed, including mixed breeds
  • Penicillamine usually for 6 to 9 months, with a copper-restricted diet
  • Progress followed by ALT or repeat copper measurement

  Who the evidence is about. A practice-oriented review for veterinarians. It states that copper-associated hepatitis can occur in dogs of other breeds or mixed breed, which is relevant to a Shih Tzu mix.

  Checked against the sourceCopper Hepatopathy in Dogs (Clinical reference · Today's Veterinary Practice (Tinoco-Najera and Lidbury) · 2023).Read the original

• How copper-associated hepatitis is diagnosed

  Diagnosis needs a liver biopsy that shows chronic hepatitis together with copper building up in liver cells, usually around the central veins of each liver lobe. The tissue is stained for copper and the copper is also measured. Measured levels above about 1000 micrograms per gram of dry liver are typical, and the statement describes a gray zone between 600 and 1000 where the picture is judged together with the tissue findings. Copper can vary from one lobe to another, which is why samples from several lobes are advised.

  • Diagnosis needs a liver biopsy with copper staining and a copper measurement
  • Levels above about 1000 micrograms per gram dry weight are typical; 600 to 1000 is a gray zone
  • Copper varies between lobes, so samples from several lobes are advised
  • The statement advises checking every liver biopsy for copper, because it is common and treatable

  Who the evidence is about. Written by specialist veterinarians for dogs with chronic hepatitis. The evidence on copper-associated hepatitis comes mainly from Bedlington terriers, Labrador retrievers, Doberman pinschers, West Highland white terriers, Dalmatians and cocker and springer spaniels. Shih Tzus are not among the breeds with strong evidence, although copper-associated hepatitis can occur in other and mixed breeds.

  Checked against the sourceACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs (Specialist consensus statement · Journal of Veterinary Internal Medicine (Webster and colleagues) · 2019).Read the original

• Raised liver enzymes in a dog that looks well: why ALT matters

  The ACVIM consensus statement calls ALT, a liver enzyme measured on routine blood work, the earliest indicator of chronic hepatitis in dogs and the best screening test, because early signs of the disease are vague and nonspecific and obvious illness usually means a later stage. Its key point says a persistent, unexplained ALT increase lasting more than 2 months, with or without other lab changes, is the best screening test currently available for early detection. It notes that up to 20 percent of dogs with chronic hepatitis have raised liver enzymes without any clinical illness, so a dog can look fine while the disease is active. It also says tissue changes of chronic hepatitis can be present even when liver enzymes are not raised, so a normal ALT does not fully rule it out. Bile acid tests are described as too insensitive in early disease to be the reason for deciding on a biopsy.

  • ALT is described as the earliest indicator and the best screening test for chronic hepatitis in dogs
  • Key point: an unexplained ALT increase lasting more than 2 months is the best available early signal
  • Up to 20 percent of dogs with chronic hepatitis have raised enzymes but no signs of illness
  • Early signs are vague. Obvious illness usually means later-stage disease
  • A normal ALT does not completely rule chronic hepatitis out
  • Bile acid tests are too weak in early disease to decide whether to biopsy

  Who the evidence is about. Specialist consensus, based on expert opinion and published studies of dogs that have the disease. It is not a study that screened healthy dogs. It covers chronic hepatitis from any cause, not only copper. Whether and when to investigate a particular dog's liver enzymes is a decision for that dog's veterinarian.

  Checked against the sourceACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs (Specialist consensus statement · Journal of Veterinary Internal Medicine (Webster and colleagues) · 2019).Read the original

• D-penicillamine: dosing, maintenance and side effects

  D-penicillamine binds copper in the liver so that it leaves the body in urine. The statement lists a typical dose of 10 to 15 mg per kg twice daily, given 30 minutes before or 2 hours after a meal, and a lower maintenance schedule of once a day, two to three times a week, at about half the dose. Common side effects are nausea, vomiting, reduced appetite and skin reactions. Less common are protein in the urine and a raised ALP. Rare are immune reactions and bone marrow problems. Suggested ways to cope include raising the dose gradually, giving it with a small piece of meat, or adding an anti-nausea drug. The statement says that treating with penicillamine and zinc together is strictly contraindicated.

  • Typical dose 10 to 15 mg per kg twice daily, on an empty stomach
  • Maintenance: once a day, two to three times a week, at about half the dose
  • Common side effects: nausea, vomiting, reduced appetite, skin reactions
  • Penicillamine and zinc together are described as strictly contraindicated

  Who the evidence is about. Written by specialist veterinarians for dogs with chronic hepatitis. The evidence on copper-associated hepatitis comes mainly from Bedlington terriers, Labrador retrievers, Doberman pinschers, West Highland white terriers, Dalmatians and cocker and springer spaniels. Shih Tzus are not among the breeds with strong evidence, although copper-associated hepatitis can occur in other and mixed breeds.

  Checked against the sourceACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs (Specialist consensus statement · Journal of Veterinary Internal Medicine (Webster and colleagues) · 2019).Read the original

• Immune-suppressing drugs in chronic hepatitis

  Immune-mediated chronic hepatitis is presumed to occur in dogs, but there are no validated criteria or commercial tests to confirm it. The statement advises a careful search for an underlying cause, such as copper, before immune-suppressing treatment, and says such treatment should rest on tissue evidence of a suspected immune process. It does not give drug choices, doses or durations.

  • No validated test for immune-mediated hepatitis in dogs
  • Look for a primary cause such as copper before immunosuppression
  • Drug choices and durations are not covered

  Who the evidence is about. Written by specialist veterinarians for dogs with chronic hepatitis. The evidence on copper-associated hepatitis comes mainly from Bedlington terriers, Labrador retrievers, Doberman pinschers, West Highland white terriers, Dalmatians and cocker and springer spaniels. Shih Tzus are not among the breeds with strong evidence, although copper-associated hepatitis can occur in other and mixed breeds.

  Checked against the sourceACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs (Specialist consensus statement · Journal of Veterinary Internal Medicine (Webster and colleagues) · 2019).Read the original

• Copper-restricted diet for life, and zinc as maintenance

  The statement recommends a copper-restricted diet for life, at less than 0.12 mg of copper per 100 kcal, and limiting copper in drinking water (flushing copper pipes for a few minutes is suggested). It says most dogs do not need protein restricted. Zinc can be used as maintenance treatment because it makes the gut bind copper, but it works slowly and is not suited to removing copper. It is not used together with penicillamine.

  • Copper-restricted diet for life, below 0.12 mg per 100 kcal
  • Limit copper in drinking water
  • Zinc is a slow maintenance option, not a way to remove copper
  • Do not combine zinc with penicillamine

  Who the evidence is about. Written by specialist veterinarians for dogs with chronic hepatitis. The evidence on copper-associated hepatitis comes mainly from Bedlington terriers, Labrador retrievers, Doberman pinschers, West Highland white terriers, Dalmatians and cocker and springer spaniels. Shih Tzus are not among the breeds with strong evidence, although copper-associated hepatitis can occur in other and mixed breeds. A veterinary nutritionist tailors the plan to the individual dog.

  Checked against the sourceACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs (Specialist consensus statement · Journal of Veterinary Internal Medicine (Webster and colleagues) · 2019).Read the original

• Monitoring treatment response: ALT and repeat copper measurement

  A return of ALT to normal is used as a stand-in for treatment success, but ALT is not sensitive enough to show leftover mild copper accumulation. The statement recommends continuing treatment for a month after ALT normalizes. It says treatment is best judged by measuring liver copper again. With penicillamine plus a copper-restricted diet, copper up to about 1500 micrograms per gram usually normalizes within six months, and higher levels within about nine months. It does not set a fixed re-biopsy schedule or discuss tracking scarring over time.

  • Normal ALT is a stand-in for success but can miss mild leftover copper
  • Keep treating for a month after ALT normalizes
  • Repeat measurement of liver copper is described as the best check of efficacy
  • No fixed re-biopsy schedule is given

  Who the evidence is about. Written by specialist veterinarians for dogs with chronic hepatitis. The evidence on copper-associated hepatitis comes mainly from Bedlington terriers, Labrador retrievers, Doberman pinschers, West Highland white terriers, Dalmatians and cocker and springer spaniels. Shih Tzus are not among the breeds with strong evidence, although copper-associated hepatitis can occur in other and mixed breeds.

  Checked against the sourceACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs (Specialist consensus statement · Journal of Veterinary Internal Medicine (Webster and colleagues) · 2019).Read the original

• The 1 to 7 fecal score chart

  A widely used chart for describing stool. Score 1 is very hard, dry pellets. Score 2 is ideal: firm but not hard, pliable and segmented. Score 3 is log-shaped and moist, leaving a little residue but holding its form. Score 4 is very moist and soggy and loses its form when picked up. Score 5 is very moist piles with a distinct shape. Score 6 has some texture but no defined shape, in piles or spots. Score 7 is watery with no texture, in flat puddles. The chart describes appearance and is not a diagnosis.

  • Score 2 is ideal; scores 3 and 4 are softer
  • Scores 5 to 7 are progressively looser
  • It describes appearance only

  Who the evidence is about. A general fecal scoring tool for dogs. A dog's own normal can sit a point or so away from the ideal, so his own baseline matters most.

  Checked against the sourcePurina Fecal Scoring Chart (Clinical reference · Purina).Read the original

• Triglycerides and pancreatitis: what one study found

  A 2020 study compared dogs with naturally occurring pancreatitis with healthy dogs. Most dogs with pancreatitis (over 70 percent) had triglycerides within the reference interval. About 18 percent had high triglycerides, compared with 7.5 percent of healthy dogs, a difference that was not statistically significant. Samples were taken after fasting for at least 12 hours. The study measured how common high triglycerides are in pancreatitis. It does not give advice on diet or drugs, and it does not say whether very high triglycerides can contribute to pancreatitis in an individual dog.

  • Most dogs with pancreatitis had normal triglycerides
  • Blood is drawn after fasting for at least 12 hours
  • The study does not cover treatment
  • It does not rule in or out a contribution from very high triglycerides in one dog

  Who the evidence is about. General population of dogs with pancreatitis and healthy controls. The very high triglyceride level documented in the chart (above 1000 mg/dL) is far above the mild increases seen in this study, and the specialist's report states that high triglycerides can contribute to recurrent pancreatitis episodes.

  Checked against the sourceSerum triglyceride and cholesterol concentrations and lipoprotein profiles in dogs with naturally occurring pancreatitis and healthy control dogs (Peer-reviewed study · Journal of Veterinary Internal Medicine (Xenoulis and colleagues) · 2020).Read the original

• When pancreatitis blocks the bile duct: what 46 dogs showed

  A 2020 records review from one university hospital looked at 46 dogs whose pancreatitis was linked to a blocked or narrowed common bile duct, the tube that carries bile from the liver to the intestine. A dog was counted if its bilirubin reached 2.0 mg/dL or more and an ultrasound showed the common bile duct wider than 3 mm. Dogs with primary liver disease, gallbladder mucocele, bile duct tumors or obstructive gallstones were left out on purpose. Most dogs got better with medical care alone: 33 of the 42 dogs with a known outcome (79 percent) survived to leave the hospital, and 31 of those 33 had no procedure to drain the bile system. Of the 4 dogs that did have a drainage procedure, 2 died. Recovery was slow. The median time from first signs to the first fall in bilirubin was 15 days. Fever, vomiting and poor appetite often eased before bilirubin peaked, and the authors suspect those signs come mostly from the pancreatitis itself rather than the blockage, so a dog can seem better while blood tests still show it. How wide the duct was and how high the bilirubin went did not predict who survived.

  • Pancreatitis is a recognized cause of bile duct blockage in dogs
  • 33 of 42 dogs with a known outcome (79 percent) survived, and 31 of the 33 survivors needed no drainage procedure
  • Recovery was slow: about two weeks (median 15 days) from first signs to the first fall in bilirubin
  • Vomiting, fever and poor appetite often eased before bilirubin peaked, so a dog can look better while the blockage still shows in blood tests
  • Duct width and peak bilirubin did not predict survival
  • Dogs with primary liver disease were excluded, so the study cannot say whether liver disease changes the risk

  Who the evidence is about. 46 client-owned dogs seen at one university hospital between 1999 and 2017, median age 9 years, 18 breeds including 15 mixed-breed dogs and one Shih Tzu. It is a retrospective records review, so treatment varied and tests were not done on a fixed schedule. The authors could not tell acute from chronic pancreatitis without tissue samples. The study does not discuss diet, triglycerides, medications or copper, and it excluded dogs with primary liver disease.

  Checked against the sourceBile duct obstruction associated with pancreatitis in 46 dogs (Peer-reviewed study · Journal of Veterinary Internal Medicine (Wilkinson and colleagues) · 2020).Read the original