Should liver biopsy be done?

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!!!

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.

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