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Should liver biopsy be done?

Species: Dog
Breed: Maltese-Bichon
Age: 8-11 years
Dear Dr Haines,

I have a 10 year old Bichon-Poodle-Maltese mix male dog (Max). In April 2012 Max went in for a teeth cleaning under general anesthesia, and routine preop labs showed an ALT of 167 and alkaline phosphatase of 533. In October of 2012 labs were drawn again as he has a large chalazion removed under general anesthesia. His ALT was 391 and Alk Phos was 864. Our vet told us this were mildly high, but nothing too alarming. However, we tested him for Cushing’s and the test was negative. In July 2013, Max went in for another teeth cleaning. Preop labs showed ALT 491 and Alk Phos 1181. We were referred to a veterinary internal medicine specialist. The specialist did an ultrasound that showed mild bilateral adrenal gland enlargement with no evidence of masses or malignancies. He was started on Flagyl, Amoxicillin, and Denamarin at the appropriate weight based doses and given these for one month. This was done to treat any underlying infection such as cholangitis. A test for atypical Cushing’s was also done at the initial appointment and 2 weeks later came back strongly positive with significant elevations in cortisol, androstenedione, estradiol, progesterone, 17-OH Progesterone. His aldosterone was normal. So, we were planning on starting Lysodren. However, we decided to wait for 2 weeks to start the Lysodren so we could compete the 1-month of antibiotics and Denamarin. At completion of the month, we did labs again with ALT being 632 and Alk Phos 1508. So, the increase in ALT was greater in the last 30 days than they had been increasing the last 9 months or so. Since these labs are worse, my vet specialist feels that something more than atypical Cushing’s hepatopathy is going and would like to proceed with an open liver biopsy and exploration. Naturally, we are not excited about the lab results or the possibility of an open surgery. The surgeon feels Max is too small for a laparoscopic procedure and a FNA biopsy is too limiting. Of note, Max is appears completely asymptomatic and is otherwise healthy. All of labs values including albumin, amylase, BUN, glucose, WBCs, etc are normal. A couple of questions:

1. Is it reasonable to assume that Flagyl may be responsible for the increased liver enzymes in the last month? If yes, how long does it typically take for them return to a baseline unaffected by Flagyl?
2. Would you recommend an open biopsy at this point? Should we wait a month after stopping Flagyl to see if ALT and Alk Phos go down to pre-Flagyl values or even improve with the Denamarin? If the labs go back down after stopping Flagyl would you recommend a liver biopsy or starting Lysodren for the atypical Cushings? We are aware that the Lysodren can negatively affect the liver.
3. Is the extent of his labs values suggestive of another disease process besides atypical Cushings? What else should we consider testing him for?

Thanks so much for your help!!!

Online vet, Dr. Marie

Dr. Marie replied:

Hi and thanks for your questions.

Metronidazole (Flagyl) can make liver enzymes appear higher than normal. I don't know exactly how long it will take for the enzymes to come down, but I would assume that within 1-2 weeks of being off of Flagyl the results should be much better if the Flagyl was the cause.

The biopsy is a tough call especially given that Max is generally feeling well. There are obviously pros and cons to doing it. If there was something treatable lurking there then it would be better to find out sooner rather than later. However, if the elevated ALT is due to the Flagyl then it may be unnecessary. This decision is really one that you need to make with the help of your vet though.

As soon as you mentioned that there was an elevated ALP that kept going up I thought that perhaps this was atypical Cushings. Most times when I see a dog with an increasing ALP they usually end up getting Cushing's disease.

My personal philosophy is not to treat Cushing's until a dog has clinical signs such as an excessive thirst and urination. I might be hesitant to put a dog on Lysodren if there were no clinical signs.

I'm reluctant to give too much advice here because there are a lot of details to this case and I don't have all of the details and also obviously cannot examine Max.

If you are really uncertain, it's not a bad idea to consider getting a second opinion from a vet in your area. You can take the lab work that you have and a copy of his records and have another vet examine Max and give their thoughts. It never hurts to do that.

It does sound like your vet is being very thorough and this is a good thing. I think that it is reasonable to ask them if waiting for now is a reasonable option.

Cases like this are tough.

Please let me know if you have more questions.

Dr. Marie.

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Disclaimer: Although Dr. Marie is a qualified veterinarian, the information found on this site is not meant to replace the advice of your own veterinarian. and Dr. Marie do not accept any responsibility for any loss, damage, injury, death, or disease which may arise from reliance on information contained on this site. Do not use information found on this site for diagnosing or treating your pet. Anything you read here is for information only.

Customer reply:

Hi Dr. Marie,

Thank you for your timely response. One lab I did forget to mention was a bile acid study. His pre was 53 and post was 43. He therefore does have some liver dysfunction hence we wanted to proceed with the Lysodren for Cushings "induced" liver disease. He does seem to have some increased thirst but we have measured his water intake and it is around 150-200mL per day (he is about 10 lbs). He does have some alopecia in the last 6 months, although it is somewhat subtle. My only other question would be about Flagyl. Is ALT/Alk phos elevation due to Flagyl a common reaction to have, or is this more of an uncommon reaction to have? I guess if it was common we would be more willing to wait a few weeks and determine if the LFTs went down s/p Flagyl, but if it was an uncommon reaction, we might be more inclined to proceed with a biopsy. Thanks again. Appreciate your insight.

Online vet, Dr. Marie

Dr. Marie replied:

These are tough questions to answer. The majority of animals that I would put on Flagyl are on a very short term such as a 5 day course because of diarrhea. I don't think it would happen often that I would have blood tests done while a pet is on Flagyl so it would be hard to say whether it is common.

From what you have described it really sounds like there is no harm in waiting to see what the liver enzymes do over the next two weeks and then make your decisions based on those results.

Dr. Marie

Customer reply:

Thanks much for your help. Best wishes for the future.

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Dr. MarieDr. Marie is a veterinarian who practices in a busy animal hospital in Ottawa, Ontario. She created Ask A Vet Question as a resource for good, accurate veterinary advice online. Dr. Marie treats dogs, cats, hamsters, guinea pigs, and rats. She has been a vet since 1999.

Is an online vet visit just as good as a trip to your veterinarian? No! But, many times, asking an online veterinarian a question can help save you money. While Dr. Marie can't officially diagnose your pet or prescribe medications, she can often advise you on whether a vet visit is necessary. You can also ask Dr. Marie for a second opinion on your pet's condition.