Chronic Liver disease in dogs Flashcards
Name causes of chronic liver disease?
Idiopathic chronic hepatitis:
- most common liver disease in dogs
- cause unknown
- several breed predispositions
Copper-associated liver disease:
- associated with some specific breeds
- Labrador retriever, Dalmatian, Sky terrier, Doberman pinscher
- WHWT: some (but not all) have copper accumulation
True copper storage disease
- Bedlington terriers (Has improved since appropriate breeding.)
Discuss copper associated liver disease?
We don’t know for sure whether the copper accumulates and causes the problem or the liver isn’t handling it right and then it accumulates.
Discuss chronic liver disease causes?
Congenital vascular disease
- e.g. congenital portosystemic shunts (cPSS)
Neoplasia:
primary
- hepatocellular carcinoma
- lymphoma
Secondary
- very common site for metastases
- can be clinically silent
- can haemorrhage e.g metastasis from splenic haemangiosarcoma
Biliary tract disease
- biliary mucoceles
- neutrophilic cholangitis
- extrahepatic bile duct obstruction
- bile duct rupture
Discuss benign nodular hyperplasia?
- Benign nodular hyperplasia is common in dogs
- Nodular hyperplasia occurs as a benign, age-related microscopic or grossly apparent small mass lesion in dogs.
- It may be confused histologically with adenomatous hyperplasia or hepatic adenoma. Although nodular hyperplasia does not cause clinical disease, it can be accompanied by increased liver enzyme activity, particularly ALP.
- Ultrasonographically, nodular hyperplasia is associated with hypoechoic hepatic nodules set against a hyperechoic background
- Cytology of an aspirate may discriminate dysplastic, neoplastic, or inflammatory cells but cannot exclude any of these disorders.
- Biopsy is necessary to differentiate between nodular hyperplasia, dysplastic microscopic nodules, regenerative nodules, cirrhosis, and neoplasia.
What is important to remember about this picture?
We need to know: does the patient have a 1ry or a 2ry hepatopathy?
Cushinoid dogs are a reminder of 2ry hepatopathy only pursue the liver if it is 1ry liver disease not something 2ry causing liver disease like HAC
What might this liver look on ultrasound?
Changes within liver will be shown on biopsy not on US
Describe canine chronic hepatitis histologically?
“Typical” histopathology shows:
- a variable mononuclear or mixed inflammatory infiltrate
- hepatocellular apoptosis or necrosis
- regeneration and fibrosis
- Not very neutrophillic it will be lymphocytic and plasmacytic which is indicative of inflammatory reaction
How common is canine chronic hepatitis?
Post mortem prevalence of 12% in the UK
- this means it is a common liver disease
↑ prevalence in certain breeds in UK:
- Cairn terrier
- Dalmatian
- Doberman Pinscher
- English Cocker spaniel
- English Springer spaniel (love to get pancreatitis and liver disease)
- Labrador Retriever
More common in middle-aged and older animals
Case study Ellie:
Ellie Signalment:
5 year old FE English Springer
Presenting signs:
- Several week history of:
- lethargy
- intermittentV/D
- progressive ↓ in appetite
- weight loss
- possibly drinking more?
Physical Examination
- T 38.7C, HR 120, RR 22
- Depressed/dull
- Poor body condition
- ~10% dehydrated
- Jaundiced skin, sclera, mm
- Painful cranial abdomen
- Otherwise unremarkable
Ellie is jaundiced- why might this be?
Pre-hepatic jaundice
- Causes include intravascular or extravascular haemolysis (e.g. immune mediated)
- what is the PCV/red cell count? Using this can rule this out very quickly
Hepatic jaundice
Post-hepatic jaundice
- causes include pancreatitis, pancreatic neoplasia, cholelithiasis, biliary tract rupture
What do we expect in the clinical history of canine chronic hepatitis?
Waxing and waning non specific clinical signs including:
- inappetence
- weight loss
- vomiting +/-haematemesis if GI ulceration
- diarrhoea +/-melena
- PU/PD
- lethargy, depression –> true neuro signs/HE?
Early signs can be missed or misdiagnosed as self limiting GI disease
- Dogs present in an “acute” crisis but could be “acute on chronic” disease (A chronic disease can present as an acute final straw situation)
- Remember: an acute presentation does not always mean an acute disease…the “final straw” in chronic disease means a sudden deterioration can be misinterpreted as a disease of sudden and recent onset.
What do we expect on physical examination of dog with chronic canine hepatitis?
Findings will vary hugely with the stage of disease at presentation
- Often very non-specific
Important clinical findings include:
- poor body condition
- jaundice
- ascites
These cases remind us of the importance of reviewing a case that is not responding as you expect, for example
- A dog with repeat visits for V/D not responding to diet management
- A dog with variable appetite that is now showing weight loss
What do we expect on biochemistry of chronic canine hepatitis?
Liver enzymes
- variable in ALT and ALP
- may be within the reference range in end stage disease due to loss of hepatocytes (not common but can happen)
Markers of liver function
- Drop in albumin
- Drop in urea
- Increase in bilirubin
- Increase inbile acids (fasting and post prandial)
- Increase in NH3 (not a useful clinical test in many cases)
- Prolonged coagulation times
What do we expect to see on diagnostic imaging of canine chronic hepatitis?
Radiography
- changes can be very non specific
- technique has poor sensitivity
- might see a small liver (upright stomach axis)
- is there any loss of serosaldetail suggesting ascites?
Ultrasound
- might get the impression the liver is small (less objective than radiography)
- irregular liver margination
- variable echogenicity: often patchy hyper-and hypoechogenicity
- ascites
- acquired PS shunts (typically seen caudal to L kidney)
Comment on Ellie’s US?
- Liver appears small, heterogeneous echogenicity, irregular outline.
- Moderate amount of free fluid present.
What is your diagnosis based on Ellie’s histology report?
- There are moderate amounts of inflammatory cells present throughout the hepatic parenchyma
- Bridging fibrosis is present and there is some evidence of regeneration but damage appears to be ongoing
- Areas of cell death are present (necrosis)
- No obvious causative agent can be identified
- FISH –ve for leptospira organisms
Chronic canine hepatitis
How do we manage chronic canine hepatitis?
How do we manage this disease?
- Unknown aetiology means specific treatments are not possible
Non-specific treatment is appropriate in order to?
- slow progression of disease
- control and relieve the clinical signs
- improve quality of life
- possibly prolong survival (a 2ry aim iequality > quantity)
Early diagnosis and treatment can slow progressive fibrosis –> cirrhosis
Dietary management to support the liver is very important
What drugs are commonly used to treat chronic liver disease?
- Destolit (ursodeoxycholicacid)
- Antioxidants: SAMe, Silybin, vitamin E
- Corticosteroids
- Antibiotics
- Diuretics
What is the justification for UDA (ursoedoxycholic acid)?
- UDA is a hydrophilic bile acid which displaces hydrophobic bile acids
- Draws water in to bile: it has choleretic effects
- is immune-modulating
- prevents cells entering the apoptosis pathway
- Increases the production of glutathione which has a useful antioxidant mechanism in the liver
Discuss UDA as a drug?
Ursodeoxycholic acid is a good drug and is useful in most liver diseases
What is the justfication for antioxidants in chronic liver disease?
- Oxidative damage from reactive oxygen species (ROS) is common in many hepatopathies including chronic hepatitis
- Glutathione (GSH) is the main antioxidant used by the liver to protect against oxidative damage (this is what UDA stimulates increased productino of)
Why do dogs with liver disease get ascites?
Splanchnic circulation = blood flow to abdominal GI organs including stomach, liver, spleen, pancreas, SI and LI
RAAS= renin angiotensin aldosterone system
Discuss copper associated liver disease?
Breeds reported in the UK include:
- Dalmations, Labradors, Skye terriers, West Highland White terriers and Dobermans
Unclear if Cu accumulation is 1ry or 2ry
- copper might accumulate in dogs with chronic hepatitis rather than be a cause of it
- There is a lot we don’t know but worth asking for copper stains and assays on all liver biopsies?
What does a portosystemic shunt look like?
What are the clinical signs of hepatic neoplasia?
often non-specific clinical signs
- lethargy, poor appetite
Signs may be associated with a complication
- abdominal bleed?
Palpable mass may be only sign
Signs as for chronic chronic hepatitis
