Metabolic Diseases of the Liver

Question 1

List the common causes of a secondary vacuolar hepatopathies in dogs and cats

Answer 1

Steroid Hepatopathy:

1. Hyperadrenocorticism: endogenous or exogenous
2. Vacuolar hepatopahty of Scottish Terriers
3. Deficiency or Toxicosis: cobalamin deficiency
4. Secondary to hepatic insult - hypoxia, right sided CHF, neoplasia, numerous extra-hepatic disease (gut, renal, pancreatic)

Steatosis:

1. Feline hepatic lipidosis
2. Toxicosis - alflatoxin, Vitamin A intoxication
3. Canine hyperlipidaemia
4. Endocrine disease: diabetes mellitus, hypothyroidism

Question 2

What are the common clinical findings in Scottish Terriers with vacuolar hepatopathy?

To what conditions does this hepatopathy predispose?

Answer 2

• The most common clinical signs include those similar to hyperadrenocorticism.
  
  • Pot-bellied appearance, PU/PD, hepatomegaly
  • Acute abdominal haemorrhage may be seen with rupture of hepatocellular neoplasm
• There is a significant increased risk of hepatocellular neoplasms in Scottish Terriers
• Gallbladder mucocoele are also over-reported in Scottish Terriers with hyperalkalinephosphatasaemia

Question 3

What are the clinicopathological features of the vacuolar hepatopathy seen in Scottish Terriers?

What are the management and treatment options?

Answer 3

• A moderate to marked increase in ALKP is typical, with milder increases in ALT
• Adrenal function testing is inconsistent with elevations in progesterone and androstenedione with ACTH stim testin most common
• Poor responses to trilostane and mitotane are frequently reported
• No specific management or treatment recommendations are defined
• sAME may be beneficial given that reduced glutathione levels have been described in association with other vacuolar hepatopathies
• Regular monitoring of the liver for development of masses or gallbladder mucocoele could be considered
  
  • There is no specific recommendation for cholerhetic treatment, though UDCA could also be indicated for theoretical benefits

Question 4

Describe the differences between hepatic steatosis seen in dogs and cats.

What are the common triggers in each species and what are the likely outcomes

Answer 4

• Hepatic steatosis has many causes in both species as a result of hepatocyte injury
  
  • Dog: alflatoxicosis, DM, hyperlipidaemia, hypoT
  • Cat: vitamin A toxicosis, severe anorexia or chronic rapid weight loss
• Steatosis in dogs can become severe is diseases such as diabetes mellitus, but it is rarely associated with significant hepatic inflammation. Hepatic dysfunction secondary to steatosis in dogs is rare
• In cats, prolonged fasting for any reason can cause hepatic steatosis / hepatic lipidosis.
• With feline hepatic lipidosis, the fat accumulation becomes so severe that the hepatocytes can no longer function adequately and acute albeit reversible liver failure can occur

Question 5

Describe the proposed pathophysiological mechanisms that contribute to the development of feline hepatic lipidosis.

Answer 5

• Obesity, stress and anorexia are all important
• Primary HL occurs in overweight cats that have been fasted - no identifiable underlying disease
• Secondary HL occurs with other disease such as IBD, neoplasia, pancreatitis, cholangitis, DM, hyperT
• In both primary and secondary HL, stress and fasting increase peripheral lipolysis and the mobilized lipids become “trapped”within the liver. Reduced hepatic export of lipids may occur.
• Reduced function of hormone sensitive lipase
• Increased serum beta-hydroxybutarate indicates ketogenesis
• Marked elevations in serum and hepatic triglycerides occur, while these are mobilised as evidenced by increased serum LDLP, they cannot mobilise them quickly enough to compensate
• Affected cats have normal to low insulin levels and are not insulin resistant
• Elevated adiponectin and leptin levels have been documented, suggesting relative resistance to leptin.

Question 6

Describe the common clinical history and examination findings in cats with hepatic lipidosis.

Note any differences between primary and secondary lipidosis

Answer 6

• Most affected cats have been obese, then have a period of anorexia or weight loss, followed by the clinical disease (acute hepatic insufficiency)
• Female, young to middle aged cats appear predisposed
• Idiopathic disease is more common in younger cats, secondary HL is more often seen in older cats
• Clinical signs are typical of acute hepatic insufficiency - anorexia, vomiting, weakness and weight loss.
• Hypersalivation and dullness occur with HE
• Examination findings reflect dehydration and severity of liver insufficiency. Hepatomegaly and icterus are common with severe disease.

A pre-HL illness may be seen with secondary cases. Abdominal pain may be seen with pancreatitis, or masses palpable with neoplasia.

Question 7

Describe the findings of clinicopathological and imaging tests in cats with hepatic lipidosis.

How is a diagnosis confirmed?

Answer 7

• There is typically a marked increased in ALKP without a concominant increase in GGT
  
  • Secondary HL with significant cholestasis will often have a marked increase in GGT
• Hyperbilirubinaemia is common
• Hypokalaemia is common due to anorexia / vomiting
• Hyperglycaemia is present ~ 50% of the time
• Ketosis (increased b-hydroxybutyrate) can be seen secondary to increased hepatic ketogenesis or diabetes mellitus, lipolysis and beta-oxidation of free fatty acids.

Diagnosis can only be confirmed via histopathological assessment of the liver.

FNA cytology can be indicative and is sensitive, but specificity is lacking and inflammatory or neoplastic disease can be missed

Presumptive diagnosis can be made with a combination of the history, clinical and clinicopathological findings together with ultrasound and cytology results. US can be accurate and diagnostic ~50-71% of the time.

Question 8

List and describe the treatment considerations for cats with hepatic lipidosis

Answer 8

• Supportive care
  
  • Fluid therapy and balance electrolytes
    
    • potassium supplementation
• enteral feeding
  
  • Tube feeding is essential as return to voluntary food intake can take up to 12-16 days or longer
  • cobalamin supplementation if low
• Anti-oxidant therapy may be beneficial
  
  • sAMe
  • vitamin E
• Coagulation factors may be reduced
  
  • Parenteral vitamin K
• Anti-emetics
  
  • Maropitant
• Prokinetics
  
  • Ranitidine
• Treatment for hepatic encephalopathy if required
  
  • lactulose and antibiotics

Question 9

Describe the pathophysiological mechanisms that lead to amyloidosis in dogs or cats

Answer 9

• Amyloidosis can be systemic or localised, primary (familial) or secondary
• Amyloid proteins are common and can exist in two main forms - (normal) soluble and the abnormal auto-aggregated fibrillar form of beta-pleated sheets
• For the beta-pleated sheets to develop, there must first be an increased in serum amyloid A (SAA), an acute phase protein that is produced in increased amounts with systemic inflammation
• Un-described genetic predispositions and environmental factors likely contribute to the development of amyloidosis, as not all individuals with elevated SAA develop the disease

Question 10

Describe the signalment of cats with systemic amyloidosis.

What mechanism may describe the known breed predispositions?

Answer 10

• The majority of cases of amyloidosis in cats is systemic and familial, with occasional sporadic cases reported
• The disease is most commonly seen in Abyssinian and Siamese cats.
  
  • Abyssinian cats tend to develop clinical signs due to renal medullary amyloidosis and the liver involvement is clinically mild
  • Siamese cats tend to present with hepatic disease due to amyloid deposition
• Siamese cats with hepatic amyloidosis can present with either hepatic rupture and acute/repeat haemorrhage or jaundice and hepatomegaly
• Abyssinian cats tend to present with clinical signs of a protein losing nephropathy. An elevated uSAA:Cr ratio may help with early detection

Both Siamese and Abyssinian cats have been shown to produce a unique, mutated form of SAA. The isomer is different in each breed and the differences may predispose to amyloidosis and explain the variable presentation of disease in each breed. The mechanisms of disease development are not known.

Question 11

What are the common clinicopathological and imaging findings in cats with hepatic amyloidosis

Answer 11

• Generally there is a mild to marked increase in ALT and globulins with minimal elevation in the biliary enzymes. Bilirubin may also be increased due to hepatic causes
• Azotaemia may or may not be present.
• Ultrasonography is likely to reveal an enlarged and diffusely hyperechoic liver with a normal biliary tree
  
  • Major differentials would include hepatic lipidosis (+FIP / lymphoma)
• FNA and cytology of the liver is rarely diagnostic and core biopsy carries a significant risk of procedural haemorrhage. Cytology may help to exclude lipidosis but cannot reliably exclude lymphoma.