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Chronic Active Hepatitis, Choleangiohepatitis

also see Diabetes
also see Liver disease

Nicky's liver biopsy update - portal hepatitis

Question: Dear Dr. Richards:

I had previously written to you about elevated ALKP and ALT levels in my 7-year-old male Standard Poodle. Thank you for your informative response. We now have a working diagnosis, much to my relief.

The liver biopsy results indicate that Nicky has "portal hepatitis," which had been characterized by the pathologist as "mild to moderate." The internist had retained a portion of the liver specimen and is sending it to be tested for copper levels as a precaution to be sure that that issue is not overlooked.

The doctor said that hepatic cancer has been ruled out, as was gallbladder disease and chronic active hepatitis. The plan is to monitor the liver enzymes and bile acids periodically and indefinitely. The doctor said that various medications can be used, as well as special diets for liver disease, but in the absence of clinical symptoms, no decision has yet been made to initiate any of those options. We'll regroup after the copper study results come back and see where else we go from here.

I've searched to find out more about "portal hepatitis," but have only seen information on "portal hypertension" and "portosystemic shunts." I also found information on "chronic active hepatitis," which I'm told is a different disease entity than what Nicky has. Although Nicky's liver is certainly not normal, I get the sense in speaking with the doctor that the portal hepatitis diagnosis was relatively good news when compared with some of the other possibilities.

I would appreciate it if you could give me a bit more information about portal hepatitis, as well as some general information about the medical management of this disease.

As always, I remain grateful for your efforts to educate and inform and for the assistance you provide.

Karen

Answer: Karen-

I think that the term "portal hepatitis" just refers to inflammation of the liver in the region of the portal veins, I think. I am not a pathologist and this may be an incorrect interpretation of the lab report. If this is the case, the diagnosis is not specific, as it gives the anatomic location but not much indication of the cause of the problem, except to help rule out the conditions mentioned, although it is my impression that portal inflammation does occur with chronic active hepatitis (although there are other signs of this condition, such as fibrosis and bile duct inflammation, which may not be present, allowing it to be ruled out).

I can't recall a specific disease referred to as "portal hepatitis" in dogs but there is a condition that is pretty common in cats, which is referred to as lymphocytic portal hepatitis. This condition is pretty benign and treatment is often not necessary, although monitoring of liver enzyme levels is recommended. Since that sounds like the advice you are getting, perhaps this condition has been recognized in dogs and I am just not aware of it yet.

I would think that an internal medicine specialist would be much more experienced than I am at interpreting the meaning of the pathology report and providing a prognosis based on it, so I am hopeful that you can count on this as good news.

Mike Richards, DVM 2/22/2001

"Doberman hepatitis" and dilated cardiomyopathy

Question: hello! i'm a new subscriber. thanks for listening, i thought your site was excellent. my 2 1/2 year male doberman is having problems, and so far we've had no luck with diagnosing his problem. in oct., we noticed he suddenly seemed to have blown up overnight. he seemed fine, just really thick in his middle. i fed him less, exercised him more, and in a few days he was back to normal. immediately after this, he started drinking excessively, and wetting the floor. we took him to vet. he has a very small liver, had elevated liver enzymes, and his organs were separated by excess fluid in his abdomed. he is very deep chested, and some of his organs are sitting into his ribcage, rather than in his abdomen area. biopsy, ultrasound, much bloodworks nd urine samples (and $$) later, still nothing conclusive. maybe liver disease? cancer? took him to another vet who said possible diabetes insipidus, though not definite. in a month, dog has lost 3 1/2 lbs., despite the fact that he eats (although he is picky). gums are very pale. he is prone to shaking, and seems lethargic and disoriented. this is especially at night. he eats 2X/day. doc put him on carb. diet, and pills to increase his appetite. no answers. just an unhappy dog. sometimes i watch to make sure his heart is beating, he seems so weak. other times, he is racing around, and can't wait to run at the park. any ideas? thanks for your time. nancy

Answer: Nancy-

Dobermans have two breed related problems that could be causing the problems that you are seeing. The most likely one is a condition that is sometimes referred to as "Doberman hepatitis", although it does occur in other dog breeds. This is actually a form of chronic active hepatitis. There is often copper accumulation in the liver with this condition in dobermans and testing biopsy samples for copper levels may be helpful in making a diagnosis, although it is usually possible for the pathologist to identify the condition without this testing. It does seem odd that are not enough changes in liver related blood values to confirm hepatitis if this condition is present and it is usually possible to identify it on a biopsy sample since it tends to be a condition that involves most of the liver. It is not unusual to have increased drinking and urinating with liver disease and it is a more common cause of this type of behavior than diabetes insipidus, although liver disease is considered to be a cause for diabetes insipidus of nephrogenic origin (occurs because the kidneys can not respond to the antidiuretic hormones produced by the body due to interference from another problem). Chronic active hepatitis is reported to be most common in middle aged female dobermans but it can occur in males and at other ages. This condition normally causes persistent increases in ALT and alkaline phosphatase levels and should cause rises in serum bile acid levels, as well. It may respond to treatment with corticosteroids or other immunosuppressive medications such as azathioprine (Imuran Rx). Ursodiol (Actigal Rx) is helpful in some patients. SAMe (DenosySD4 tm) is reported to help many patients with this condition. Antibiotics are helpful if there is any bacterial involvement. Bacteria don't cause this problem but they can invade since the liver defense mechanisms are compromised. If there is copper accumulation it can help to use medications to treat this problem, such as penicillamine. Some vets have used cholchicine for chronic active hepatitis but we have not tried this since it may have severe side effects such as hemorrhagic diarrhea and the success of the medication seems pretty variable in reports. The prognosis for dobermans with chronic active hepatitis is not very good, unfortunately. As a breed, dobermans seem to have a more severe form of this condition than often occurs.

If there really is not enough evidence to really believe that liver disease is present, the other thing that comes to mind is dilated cardiomyopathy. This is weakness of the heart muscles and is a condition which dobermans are also prone to. It can cause the fluid accumulation seen and the small liver might be just an anomoly that is confusing the issue. This is also usually a middle aged disease but it is more common in male dobermans than females and has been reported in dobermans as young as one year of age. There is usually a heart murmur associated with this condition but it is reported to be pretty subtle in some dogs and could be missed on a physical exam or may not be present. For some reason dobermans also seem to have the worst prognosis among patients with dilated cardiomyopathy, too. This condition is treated with angiotensin-converting enzyme inhibitors (ACE inhibitors, enalapril (Enacard Rx)), digoxin, furosemide (a diuretic), carnitine and/or taurine supplementation and therapy for arrhythmias that may be present.

I can't relate this to the clinical signs, except the pale gums, but dobermans also have a high incidence of von Willebrand's disease (inhibition of platelet function) which might lead to the pale gums since it is a bleeding disorder.

I know that it is frustrating to have done the right kind of work up and still not have an answer. Although it is hard to contemplate, repeating some of the testing may be necessary to get to a diagnosis, especially the liver biopsy. I wish that I had better advice to give.

Mike Richards, DVM 2/7/2001

Cholangio Hepatitis in Basenji

Question: Dear Dr. Richards, The results are back. Sasha's thyroid came back normal and her bile acids were normal. The next step was an ultrasound biopsy. The ultrasound indicated that the liver was enlarged slightly. The Vet also said her bile was "sludgy". I Then made the decision to have the biopsy done. Those results indicate that Sasha has moderate Choleangio Hepatitis. As a result of the diagnosis, Sasha has been placed on Prednisone, 10mg twice daily & Cephalexin 250mg twice daily. In addition was placed on Actigall 150 mg daily for the sludgy bile. I am very interested in what information you can give me about her type of hepatitis, and what, if any results you have seen with homeopathic therapy/Nutrition therapy, as well as any specific recommendations you may have. You asked for lab data. I have requested a faxed copy of the biopsy specific findings, and when I receive them I will forward them on to you. It sounds like you were right on with your sense of her situation when you e-mailed me. Dr R (the Vet Internest that I took Sasha to) recommends that Sasha be on the steroids for long term, and that it is difficult to tell if the liver inflammation is going down by checking the ALT level, since steroids elevate the liver enzymes. She said the only accurate way of telling is by re-biopsy in 6 months. Is that your experience as well? Thank you for your time and expertise. Sincerely, Linda

Answer: Linda-

There is a strong consensus among the veterinary specialists that rechecking biopsy samples is the only accurate way to assess the progress of chronic liver diseases.

The newest recommendation for helping with liver disease is the use of SAMe ( S-adenosylmethionine, brand name Denosyl SD4). Its use is being promoted by some of the leading experts on liver disease so it seems reasonable to try it. I don't really understand Chinese herbalism, which seems to use a lot of mixed ingrediets. Individual herbs that are supposed to help with liver disease are milk thistle and turmeric.

Hope this helps some.

Mike Richards, DVM 2/2/2001

Liver function in Basenji - possibly hepatitis

Question: Dear Dr. Richards, Brief History: Sasha is our 10 year old female Basenji. Sasha has been a healthy, active girl with no apparant changes in her activity level or wellness level. She has been seen in the past year for scooting, and has had anal gland reduction once. The Vet has kept an eye on a cyst on her left lower eyelid, and it finally got too big to watch. The determination was made to remove the cyst this month. Her diet is IAMS mini chunks, 3/4 cup daily. She weighs 22.5 pounds. Question: In this early stage of Sasha's elevated ALT level, are we doing everything possible to determine a diagnoses? Problem: Sasha had minor surgery to remove the cyst on her lower eyelid on 12/6/2000. She also had her teeth cleaned. Pre-Op bloodwork determined that her ALT level was 200. The Vet thought the cells could have become fractured in the vacutainer, so she drew a repeat sample when I took Sasha in a week later for suture removal. This time she drew the blood in a syringe. The level the 2nd time was 248. Blood sugar normal. She ruled out diabetes. She ruled out one of the thyroids--hypo or hyper, I don't remember which. She asked me if Sasha was on any vitamins or medicines. Other than the Benedryl: 1: bid for itching & swelling after eye surgery, the answer was no. Sasha received 3 doses of Frontline, one month apart, in June, July and August of 2000. She also was given chewable Heartgard from March to October 2000. Other than ProDerma in June - August, an essential Fatty Acid for her coat, she's received nothing. On Wed., I took her in for a fasting Complete Thyroid Workup (which was sent to Michigan SU Lab) and a Bile Acid Test (which was sent to Texas A & M Lab). Results will be back in one week. I am told that ultimately a Liver Ultrasound and then a liver biopsy may be needed if the liver bile test is conclusive. My breeder suggests a liver tumor, as does my Vet. Do you have any recommendations? Thank you very much for your time. Linda

Answer: Linda-

I am hoping that the liver function test and thyroid tests are back and that you have a clearer picture of what is going on.

If the bile acid response test came back normal, which is likely, I would be tempted to wait a few weeks and retest. We see a fair number of patients who have rises in ALT levels that self correct with no treatment. During the time you are waiting to retest this enzyme level you do have to monitor for signs of weight loss, decreased activity or decrease in appetite that signal a need a to be more aggressive about the diagnostic process.

An ultrasound examination of the liver is a good way to look for tumors and gall bladder problems. Biopsy of the liver is the only way to get a diagnosis for many of the conditions that affect dog's livers, such as chronic immune mediated hepatitis. It can be helpful in identifying tumors but the biopsy sample must include a section of the liver with the tumor in it. Due to this, it is hard to be certain that a tumor isn't present, even with negative biopsy samples.

My experience has been that liver disorders such as chronic active hepatitis or chronic immune mediated hepatitis are more common than liver tumors. We have had a number of dogs who had acute liver injuries causing rises in ALT that have cleared up with no specific therapy (and no diagnosis), so that seems like a reasonable possibility, too. I am hoping the diagnostic process has pointed in this direction rather than towards a tumor.

We have not seen rises in ALT levels very often in dogs with hypothyroidism but I have seen some references to this in the literature. Hypothyroidism is pretty common so it is worth ruling it out, anyway.

Please feel free to send additional questions or lab data. I can not be certain when we will get caught up on questions again but I am really hoping that it will be within the next couple of weeks.

Mike Richards, DVM 1/29/2001

Chronic active hepatitis and diabetes in Westie with Heart Murmur

Question: Hi Dr. Richards,

I am a new subscriber to VetInfo Digest, and I am writing this message from my wife's computer . I discovered VetInfo when surfing the Web for information regarding our pet's illness and was thrilled to discover this invaluable source of information. Many thanks for all that you do.

Our Westie, Abbie (who will be 10 in December) was diagnosed with chronic active hepatits on Sept. 15, a diagnosis made on the basis of an extensive blood profile, an ultrasound, and a fine needle aspirate. According to the report that we received, "the most notable physical finding was jaundice (icterus). A grade 1/6 mitral murmur was audible? A normal sinus arrhythmia was present. Laboratory findings (increased bilirubin which is causing the jaundice, extreme elevantion of bile acids and liver enzymes) all indicate active liver disease (hepatocellular damage and biliary stasis). On radiographs, heart size was normal and no abdominal abnormalities were noted. On ultrasound, abnormalities were restricted to the liver as follows: Despite the radiographs, overall the liver appeared smaller than normal -- the liver a diffuse, inhomogenous pattern most consistent with inflammation or diffuse neoplasia (particularly lymphosarcoma). The gall bladder wall was thickened and contained considerable inspisated bile (sludge). A fine aspirate showed may hepatocytes with mesothelial cells indicateive of chronic inflammation, but no cancer cells. This finding reliably rules out hepatic cancer."

Lab work at that time (9/13) revealed the following pertinent values:

Urea nitrogen - 8 ALK Phos. - 1365 ALK Phos w/Levam - 154 ALT - 561 LEV resistance - 11 Glucose - 189 Platelets - 122 PLT EST - Clumps WBC - 11.8 Total bilirubin - 3.2 Bile acids 78.2

Based on the above Abbie was started on prednisone (10 mg./day), Amoxicillin 250 mg. 4x/day, colchicine 0.3/day, and actigall 150 mg. day.

On October 4, Abbie returned for a check-up. The lab work done was not as extensive as before. Pertinent lab values were:

Urea nitroget - 10 ALK Phos. - 960 ALK Phos. w/Levam - 228 ALT - 197 Lev Resistance 24 Glucose - 148 Total bilirubin - 0.5 Bile acids - 219

Based on these values, Abbie's predisone was reduced to 5 mg./day, the Amoxicillin was stopped, and the colchicine and actigall remained the same.

By mid-October, Abbie's health had declined significantly. A normally happy, active pet, she had very little zest for life, had a voracious appetite (prednisone?) and drank copious amounts of water -- 3 to 4 times what she ordinarily drank. Concerned about Abbie's failing health, on October 18,we took her back to her vet (who has treated her since birth), and lab work done that day revealed:

Urea nitrogen - 11 ALK Phos. - 1747 ALT - 281 Glucose - 489 WBC - 22.8 Total bilirubin - 0.6

Abbie was diagnosed with diabetes. The prednisone (which she had been on for almost a month -- either at 10 mg./day or 5 mg./day -- was immediately stopped. The vet believed that the prednisone was responsible for the sudden onset of diabetes (although her glucose levels were a bit elevated according the 9/13 and 10/13 lab work). In the place of prednisone, Abbie was started on 12.5 mg. of azathioprine, which she takes every 48 hours. Amoxicillin (250 mg 2x/day) was reinstated. Abbie remained on the colchicine and actigall. On October 18 (the date of the lab work), I asked the vet if Abbie needed to be on a special diet (she has always eaten a lamb/rice) diet, and he started her on Hill's L/D. However, when the lab work the next day revealed that Abbie also had diabetes, Hill's W/D was substituted for L/D.

After being diagnosed with diabetes on October 18, we started giving Abbie 5 units of Humulin Lente once daily. During the past week, she has had 3 glucose curves, and her glucose has remained in the 400s throughout the day (every two hours). Yesterday (after the 3rd curve), her insulin was increased to 5 units of Humulin/ twice daily.

Here is our current predicament: Abbie is eating very little, yet she acts hungry. She rejects even the foods that were once given to her only as special treats (e.g., baked chicken and rice, eggs, etc.). Today, for example, she has eaten 1 dog biscuit and 1 baked chicken breast. Some of Abbie's "spunk" has returned, but she doesn't have the energy and enthusiasm that she had 6 weeks ago. Abbie returns to the vet on Friday for her 4th glucose curve.

Can a pet who has both chronic active hepatits and diabetes be treated "successully"? (It appears that treatment for the hepatitis -- prednisone -- isn't advised for the diabetes.) Can you shed any light on her overall situation? She is a very beloved pet, and we are uncertain what to anticipate with the simultaneous occurrence of these medical problems. I believe our vet is being is open with us as he can be. However, I think this situation has him perplexed as well. We knew that the liver disease might go into remission, but what does the onset of the diabetes mean? (By the way, Abbie's lab work at an April 2000 vet check-up revealed all values to be within normal range.)

We don't want Abbie to suffer in any way, and we don't want her last days to be spent at a vet's office having glucose curves performed if it's likely that her prognosis from the liver disease alone is very poor. Would you please share your candid thoughts with us?

Many thanks, Tom

Answer: Tom-

It is always harder to treat two chronic conditions than one, but I do think that it is possible to manage the liver problem and diabetes at the same time in many patients. Since either condition can be hard to manage all by itself, there isn't any guarantee of success, though. In Abbie's case there is a small chance of a third problem, Cushing's disease, based on the lab work. The levamisole inhibited alkaline phosphatase level of 228 is in the range that is associated with this condition --- but it be induced by the use of prednisone and also be stressful illnesses, so this is not a sure sign of Cushing's disease, by any means. It is just something else to consider based on the lab work and because it can make it hard to control diabetes, although it is too early to worry about that, just yet.

Many cats and some dogs with liver disease appear to be hungry, approach food and then will not eat it, possibly due to nausea induced by the smell or taste of the food. When the blood sugar stays high this can also cause changes in eating habits. At this point, getting good regulation of the blood sugar is probably the most important objective and then once that is accomplished there may be improvement in the liver disease and more attention can be paid to the liver, if not. I would lean towards staying with the diet for liver problems since it may be the best long term choice but that is a open to debate and your vet may have experiences that support the decision to change to w/d (tm).

It can take as long as a couple of months for diabetic patients to really start feeling better, so it is important not to get discouraged early in the therapy for diabetes. I strongly prefer at home monitoring of blood glucose but not everyone is comfortable doing this, since it does involve learning to get a blood sample in some manner. However, many dogs will allow their owners to obtain blood by using a small gauge needle to prick the inside of the lip or an ear margin blood vessel and home glucose monitors are readily available. If you can get the diabetes under control it may help a great deal in the therapy for the liver disease since it lessens the work the liver must do to compensate for the diabetes.

You do have to evaluate Abbie's overall response to therapy. Some dogs are miserable when they have to be treated with injections and undergo lab work. Other dogs take it all in stride. The quality of Abbie's life has to be a strong consideration, so assessing how she is handling the treatment process is an important part of decision making.

I don't have a clear answer to your main question, but I do think that it is often possible to manage two or more chronic illnesses. It is just time consuming and expensive and for some dogs it is too much hassle for a good quality of life. For others, treatment doesn't even seem to phase them a bit. You'll have to judge which way Abbie feels and because you know her best, you are the best person to make that call.

Hope this helps some.

Mike Richards, DVM 11/4/2000

Chronic active hepatitis in doberman

Question: Dear Dr. Richards,

As I explained in my earlier e-mail of today, our vet has put together a summary of the situation regarding Elke, our dobermann. The following is my translation (translator's notes are in brackets) of what he sent me. I hope the acronyms in the analyses are international, because I wouldn't know where to start to translate them.

Female dobermann born on Nov. 4, 1993, weight 34 kg [75 lb on April 14], regularly vaccinated and dewormed. Gave birth most recently around Jan. 20, 2000.

Case history: - April 14, 2000: brought in for an exam due to a slight discharge from the vulva, which did not appear to be infected despite a temperature of 40°C [104°F]. Everything else appeared to be normal. Therapy prescribed: enrofloxacin + yeast for 8 days. - May 2, 2000: again brought in for an exam due to a swollen abdomen that had been noted for several days. An abdominal x-ray gave an unclear picture. Before carrying out a paracentesis, an ultrasonography was made and showed: a large quantity of liquid (ascites after uiltrasound-guided paracentesis), a liver characterized by a non-homogeneous surface and, overall, of small size, other abdominal organs normal. Collateral analyses: Hemochromocytometric: WBC: 17.2; RBC: 6.95; HGB: 20.8; HCT: 50.2; MCV: 72; MCH: 29.9; MCHC: 41.4; RDW: 13.6; PLT: 162; MPV: 7.9; PCT: 129; PDW: 10.8. Hemochemistry: UREA 35 (20-50); SGOT 80 (00-83); Tbil 1.0 (0.0-2). Diagnosis: Hepatitis, etiology unknown. Treatment: Hill's Prescription Diet h/d; nucleocides + vitamins, diuretic, yeast. - Check-up May 15, 2000: Outwardly the dog appears to be in good condition, somewhat thinner, abdomen no longer swollen and apparently normal under palpation. Feces reported to be extremely soft and frequent. Hemochemistry: Tbil 1.2; SGOT 87; ALP 586 (000-330). Urine analysis: gluc: neg.; bilirub: ++; ketones: neg.; specific weight: 1005; blood: neg.; pH: 7.5; proteins: traces; urobilinogenous: norm.; nitrites: neg.; leucocytes: neg. Treatment: as before + amoxicilline and clavulanic ac.

It would seem that, despite the treatment, and aside from the fact that the ascites has not reformed, the situation is deteriorating rather than improving. Have you any suggestions as to how we might better interpret all this? How, if possible, to determine the cause--especially if this information would be useful for treatment purposes? And, in general, how to proceed from here?

Any help you can give would be greatly appreciated. Thank you.

Best regards, Roberta

Answer: Roberta-

Even though I think it is pretty likely that your vets are correct in the diagnosis of this condition, because chronic active hepatitis is a problem in dobermans (I feel obligated to stay consistent with this spelling, even though I am perfectly willing to accept that dobermann may be more accurate). It occurs in middle aged or older female dobermans most commonly, which fits the history. However, I don't think that the diagnosis is proven at this point and I would worry about cardiomyopathy (weakness of the heart muscles) as a complicating or possibly even primary problem.

Cardiomyopathy is also a problem that occurs in dobermans more frequently than in other breeds but it usually affects male dobermans and it usually is "left sided" which means that the fluid tends to accumulate in the lungs rather than in the abdomen. Despite this, some dobermans do have ascites (fluid accumulation in the abdomen) first. These dogs will sometimes have elevations in liver enzymes due to the changes in circulation and the alkaline phosphatase level is likely to go up first.

Just to be sure that there was a liver problem, two additional lab test results would be good to have. A bile acid test or bile acid response test would be helpful. Drawing a sample and testing for bile acids can be enough to diagnose a decrease in liver function if the bile acid level is high. If it is not high, drawing a baseline sample after a twelve hour fast, then feeding a small meal and drawing blood again two hours later for a second bile acid level (a bile acid response test) can be very helpful. If the bile acids increase dramatically in the second sample, the liver isn't working as well as it should. Secondly, a liver biopsy is a really good idea in a doberman with liver disease because it helps establish a diagnosis and if it is tested for copper it helps in figuring out part of the treatment. This is a special test that has to run on a fresh sample of liver at a lab capable of doing this test -- in the US one lab that can do this is Colorado State University's vet school lab --- you would have to figure out how to get a liver sample to them overnight so it would be in good enough shape to test. Even if you can't do the test for copper, the liver biopsy can be very helpful. It is a really good idea to test blood clotting ability prior to taking a liver biopsy sample, especially if it is done surgically rather than by ultrasound guided needle biopsy. If these tests confirm that liver disease is present, it would be really reassuring. Bile acid testing is non-invasive so it is a very good test in this situation.

Cardiomyopathy can be hard to diagnose, even when there is a high degree of suspicion for it. Heart murmurs are often present, some dogs have an arrhythmia and a rapid pulse rate may be present, as well. The most reliable tests for this condition are cardiac ultrasound examination and Holter recording (long term monitoring) of the electrocardiogram.

Both cardiomyopathy and chronic active hepatitis in dobermans are thought to have strong family ties, so even though it may be a hard choice to make, if Elke dies you may be able to help her puppies and relatives by allowing a post-mortem examination, especially if her heart and liver tissues can be examined. But for now, it is better to focus on what can be done to prevent that occurrence.

In the case of hepatitis, there are a number of treatment objectives.

Controlling the ascites by using low sodium diets and diuretics is a very good idea and your vets have done this, already. You will probably need to maintain dietary sodium control, as a minimum and may need to use diuretics long term. The usual recommendation is to use a combination of spironolactone and furosemide but if your vets used something else I wouldn't argue with success.

Controlling primary or secondary bacterial infections is an important part of treatment. The antibiotics most commonly recommended are amoxicillin/clavulonic acid combinations and amoxicillin and metronidazole used together. Your vets have already done this, as well.

Trying to control inflammation is a good objective but it is important to think long and hard about how to do this. Corticosteroids, usually dexamethasone when ascites is present, help some dogs with chronic active hepatitis a great deal. They make other dogs worse. It is a hard decision to make. Our experience has been that corticosteroids make dogs with cardiomyopathy significantly worse, probably due to salt retention, so it would be a really good idea to try to be sure that wasn't a complicating problem prior to administering them.

Reducing fibrosis in the liver is helpful. Colchicine is commonly recommended for this. It can be very upsetting to the digestive tract, so it is probably better to start with low dosages and work up to therapeutic doses, to gauge how bad the GI effect are going to be. Unless there is recent work I am unaware of this drug still has to be considered unproven in veterinary medicine but anecdotal evidence suggests it helps in some cases.

SAMe (S-adenosylmethionine, Denosyl tm), which probably has other names, has been recommended for liver disease in dogs and is pretty safe. This is available over the counter (non-prescription) in the US and seems to be safe. I am not aware of controlled studies showing a benefit but again, anecdotally it is reported to be helpful.

Zinc acetate or zinc gluconate may be helpful in dobermans with chronic active hepatitis both for reduction of fibrosis and for inhibition of copper accumulation, due to competing with copper absorption from the intestines. If your vets need information on dosages for this, I think I can find the information.

Ursodeoxycholate (Actigal Rx) is a medication that helps promote bile flow and protect liver cells from damage due to more damaging forms of bile acid. It would be reasonable to use it for chronic active hepatitis in a doberman but again, there isn't a whole lot of data to show that it is highly effective.

Protecting the gastrointestinal tract from toxins is helpful when liver disease is present. It is best to avoid using cimetidine (Tagamet Rx) for this since it can interfere with some liver enzyme systems. Famotidine (Pepcid AC Rx) or ranitidine (Zantac Rx) are OK, though.

Reducing the protein in the diet is helpful, as well as reducing salt. There is a diet, l/d, made by Hills, which might be more helpful than h/d, unless cardiomyopathy is a major contributing cause to this illness.

I am assuming that the fever may have been associated with an early infection that is gone, or due to some other problem, as fever is not a consistent sign of either of the two diseases that I tend to think are most likely. If the fever persists, it would be important to consider metastatic cancer in the differential list, as it could cause fever, ascites, weight loss, elevations in liver enzymes and almost any other sign it wants to cause.

Hopefully this all helps some in thinking about treatment options. I wish that I could tell you that I thought there was something else going on, because both of these diseases do have pretty poor long term prognoses. However, figuring out what is going on, for sure, could be helpful in improving Elke's quality of life and possibly even in extending her lifespan. Even if this isn't possible, it may be helpful to try some of the medications if her condition seems to warrant doing so.

If you need clarification of any of this, or if your vets need the drug dosages, please feel free to write again.

Mike Richards, DVM 5/17/2000

Chronic active hepatitis (also called chronic canine inflammatory hepatic disease or CCIHD)

Question: Dear Dr. Mike,

I wrote you a couple of months ago, because we were just starting down the road to finding our 7 1/2 year old Westie, Angus' problems and after a long and painful (for Angus) journey here we are with a plan. Angus has had many blood tests, ultrasound, Cushing's Disease tests and finally a liver biopsy to check for cancer, all the hepatitises and Copper Storage Disease. The diagnosis is Chronic Active Hepatitis. The questions I have are with regards to his medications and methods of treatment.

Our vet has prescribed Prednisone - which we thought initially was the culprit for the peculiar enzyme levels in his blood tests. We are having a little trouble dealing with the fact that Prednisone could have been bad for him to start with, but now it's supposed to help him. Won't it just add to the problem? Also the vet is prescribing Colchizene (I am not too sure of the spelling) and he says it could give Angus an upset stomach and cause diarrhea and vomiting - the vet says it's to prevent and/or reduce scar tissue - how does that work? The only thing that makes sense to me is the addition of 400 to 600 I.U. of vitamin E per day to Angus' diet - to provide him with anti-oxidants. We are also to feed him a low calorie, high protein diet (which is what we've been feeding him all along). We question the meds because while we want Angus to feel better and have improved health we don't want to make him sick from medication. Are there alternatives? Is there something else we should be doing? If our best course of action is to give Angus the medication that makes him feel ill - is there any other thing we can give him to help him?

Angus has given us so much joy and pleasure - we only want to give him the best of care in return.

Regards, ann

Answer: Ann-

Prednisone as a treatment for chronic active hepatitis (also called chronic canine inflammatory hepatic disease or CCIHD) is based on the reasoning that this disorder often has an immune mediated component which may respond to prednisone treatment and that prednisone seems to be able to directly influence the formation of fibrosis in the liver, at least in the early stages of liver diseases in which fibrosis occurs. It can be helpful in cases of chronic active hepatitis. The downside of prednisone usage is that it can lead to gastrointestinal ulcers, it suppresses the whole immune system, which isn't always beneficial, it can make the advanced symptoms of liver disease, such as fluid accumulation in the abdomen and hepatic encephalopathy (HE) worse. HE is central nervous system damage from toxins the liver should process, leading to seizures, blindness, loss of balance and other brain disease signs.

In some dogs, prednisone will cause liver damage (steroid hepatopathy). Which dogs this will happen to is very hard to predict. Therefore, it is not unusual for a vet to be suspicious that liver disease might have been caused by prednisone only to find themselves using it when another problem seems more likely, after further testing. There is still the potential for liver problems to show up with later use of prednisone but this is really not all that common with prednisone usage.

If prednisone seems to be helping, it is reasonable to continue with it. If it isn't helping, you need to let your vet know. If Angus stops eating, starts vomiting, acts sick or just doesn't seem right to you, it is also a good idea to call your vet and arrange for a visit to be sure that the prednisone is not causing problems.

I am not a huge fan of cholchicine because I can't find studies that really support its use. However, it is a human medication that benefits some human patients and therefore it is used in dogs, hoping for similar benefits. I can't argue that logic, I just don't personally believe that there is enough proof of positive benefits, yet, to get real excited about cholchicine. Your vet may have had good experiences with this medication that make him feel confident it will have a beneficial effect. As long as it is dosed accurately cholchicine seems fairly safe. It is toxic in people at doses that are close to the therapeutic dose, though. It works through a couple of actions -- it interferes with production of collagen, an essential ingredient for scarring and it seems to increase the activity of collagenase, an enzyme that breaks down scar tissue, at least in humans.

Ursodeoxycholate (Actigal Rx) is another medication that is often mentioned as beneficial in chronic active hepatitis, also based mostly on its effect in humans. It seems to be pretty safe and we have tried this medication in our practice. Our impression is that it is helpful in some cases, although we have mostly used it in cats with cholangiohepatitis, which is a different disease. This medication helps increase bile flow and may also decrease toxic effects of normal bile acids on the liver which can occur when the bile is not moving into the intestine properly.

N-3 essential fatty acid supplementation may be helpful in reducing inflammation, as well. There are a number of essential fatty acid supplements on the market. Vitamin E as an anti-oxidant may have some protective effect, too, although I can't remember seeing a recommendation to use it in chronic active hepatitis, which doesn't mean that there hasn't been one in the literature, as it is absolutely impossible to keep up with everything in this information boom time.

I am a little confused by the dietary recommendations. In general, the recommendation for chronic liver diseases is to feed a reduced protein diet, using very high quality protein ingredients, in order to try to decrease the amount of protein by-products (ammonia, primarily) and to decrease the work-load on the liver. It might be worth checking to see if there has been a misunderstanding over this particular recommendation.

Hope this helps some.

Our personal experience with this condition has been pretty good, with most patients living with the condition successfully for several years and many making it to lifespans that would be considered to be within the "normal" range.

Mike Richards, DVM 5/4/2000

Chronic Active Hepatitis

Question: Hello!

Your site is extremely helpful and I have just submitted my subscription electronically. I have read everything available on your site re: canine liver disease and esp. chronic active hepatitis. I am trying to find our as much info as possible about the disease and treatments. My order for the Digest probably has not been processed yet, but I really need some help from Dr. Mike as quickly as possible.

Our 7 1/2 year old male Dalmatian was just diagnosed with chronic active hepatitis. He has been put on prednisone, actigall, tagament and a diuretic. I understand Milk Thistle and Aloe Vera juice might be effective in helping him, but don't know any vets who understand or prescribe holistic/natural remedies. I don't know how much time our little guy has, so time is of the essence! Also can I use natural and traditional medicines side by side? Please help! Thank you so much!!!

Kimberly

Answer: Kimberly-

How was the diagnosis of chronic active hepatitis made? Your dog is young enough that you could be treating this condition for a long time, so it would seem like a good idea to be really sure of the diagnosis. That isn't the question you asked, but it would help me to give you a better idea of what the medications are used for if I knew a little more about what happened with your dalmatian and whether the diagnosis is based on bloodwork, ultrasound exam, X-rays, liver biopsy or some combination of those diagnostic techniques.

In the meantime, I have not seen a recommendation to use aloe vera for chronic active hepatitis but can probably tell you why that might be advocated. Aloe vera contains a compound acemannan, that is thought to be an immune system modulator. Since chronic active hepatitis is now often referred to as chronic canine inflammatory hepatic disease, something that might modify the inflammatory response would seem reasonable to use. There may be some other effect of the aloe that I am unaware of, though.

Milk thistle contains silymarin which is supposed to help the liver increase protein synthesis and to have protective effects on liver cells. There are some specific references in humans for the effects of this medication (the PubMed web site is a good place to look for these, there is a link on our link page). There are no specific dosing studies for dogs that I know of but most of the recommendations I have seen have been to use the adult human dose for big dogs and less as dogs get smaller. An example would be to use about 1 capsule per day for small dogs for products that recommend 3 capsules per day for adult humans.

Most of the patients we have had in our practice who have evidence of chronic inflammatory liver disease do well and live for several years. Some don't do as well but usually this is a disorder for which long term control is a goal, rather than a disorder for which intense short term treatment is necessary. I hope that your dalmatian fits in the long term control category.

Mike Richards, DVM 1/28/2000

Chronic active hepatitis

Q: Good Evening Doctor, I have a third follow up question. My dog, Sarek's tests have been coming back much improved. Could you tell me what the normal range for ALT is? He is now at 500 (was 2000) so I realize the disease is still progressing.

Thanks, Greta

A: Greta-

The normal range for each lab that runs ALT tests is a little bit different. It is usually printed on the lab form, if you have a copy of it. However, the range is usually around 10 to 70 U/L in a dog and 10 to 50 U/L in a cat. I have seen normals listed as high as 110 for at least one lab, though. The half life of the ALT enzyme is fairly short, less than two days. This means that after a single insult to the liver with a rise in ALT, it would take 2 to 3 days to see a substantial decrease in ALT. It is a good sign that it is decreasing. I hope that continues.

Mike Richards, DVM 7/1/99

Chronic active hepatitis (also called chronic canine inflammatory hepatic disease or CCIHD)

Q: Dear Dr. I am a new subscriber. My dog is a mixed Golden and Flat Coated Retriever, 7 1/2 years old acquired at 8 weeks of age. Since pupyhood he has been hyper and I met this with daily hikes on forest trails where he did drink lake water. He has never liked to eat as is true of his sibs and has tended to loose stools. He has had regular vet care of good quality as I can judge. My only concern now is that neither the vet nor I picked up on weight until it got to nine lbs probably because of his dislike of food. The following is from his record. I take responsibility for typing errors. Biopsy Microscopic description Each of three needle biopsies contains moderate to severe periportal inflammation which bridges between portal triads and extends through the limiting plate into the hepatic parenchyma. Neutrophils, histocytes, lymphocytes, andplasma cells are identified. Moderate to focally severe bridging fibrisis is also present. Areas of necrosis are identified in the most fibrotic areas. The hepatic lobules are multinodular and show moderate to severe nonlipid cellular swelling. Moderateestasis is noted in hepatocytes. Some triads show moderate biliary hyperplasia. Pathological Diagnosis 1. Moderate to severe chronic active hepatitis with bridging fibrosis - liver 2, Patchy moderate biliary hyperplasia with cholestasis - liver 3. Moderative to severe acute hepatocacellular swelling - liver The copper stain was OK. He is on Actigall 300mg 1xday, Amoxicillin 500mg 1xday and Milk Thistle 70mg 2xday since 4/16 and Prednisone 20mg 2xday from 4/16 to 4/29 reduced by 1/2 eff 4/29. There have been no known causes and he has always acted healthy, good natured and happy. He is in Interceptor and Frontline and now eats PetGuard. His apetite is better than it has ever been but I suspect it is from the meds. Would you be kind enough to share your thoughts. I do better coping if I have lots of info. Thank you Greta

A: Greta-

You are probably correct that the appetite increases that you are seeing are due to the prednisone administration. This is a corticosteroid and a definite side effect is increased appetite. It is hard to decide how to dose prednisone -- or even when to use it -- for chronic inflammatory liver diseases. In all honesty, I think that it is necessary to dose this based on clinical experience or even just "gut feeling". The general starting dose is 0.5mg per pound of body weight, given twice a day. As clinical improvement occurs the object is to reduce the dosage to the lowest possible every other day dosage -- trying to get to around 1 mg per 5 pounds of body weight every other day, if at all possible.

Ursidiol or ursodeoxycholate (Actigall Rx) is a medication whose use in veterinary medicine is relatively new. At this time, I am not aware of scientifically validated studies supporting its use but there is good theoretical reason to use this medication and it is widely used in veterinary practices for the treatment of chronic inflammatory diseases of the liver. It works by replacing harmful bile acids that might harm the liver. In addition, it is thought to have some anti-inflammatory effects.

Antibiotics are often used to be sure that there is no infection. Bacterial infection may be one cause of chronic hepatitis in dogs. Just as importantly, dogs with hepatitis may not produce adequate immune responses to illness, leading to a higher chance for them to become ill with bacterial infections than a dog that does not have this problem.

Milk thistle is reported to be helpful in some cases, in liver disease. I do not have much information other than that on its use, though.

The pathologic diagnosis fits chronic active hepatitis (also called chronic canine inflammatory hepatic disease or CCIHD). The standard recommendation is to redo the biopsy in 6 months, or more, to see if there is a reduction in the fibrous bridging and other pathologic signs of this disorder. If not, there may be a need to adjust the treatment.

A low protein, reduced salt diet, such as Hill's k/d or Purina nf may also be helpful in reducing the liver's workload and slowing the progress of this disorder.

As time goes on, it may be necessary to treat problems related to liver failure, such as fluid accumulation in the abdomen, hepatic encephalopathy, bacterial infections and gastrointestinal protectants.

The clinical response to treatment is an important prognostic sign. It sounds like that has been very good. I think it is a good sign.