Metabolic Diseases of the Liver Chapter 285

Metabolic Diseases of the Liver

Vacuolar Hepatopathies

• Hepatocytes become swollen with fat, glycogen, or water in vacuolar hepatopathies
• Periodic acid Schiff (PAS) stains for glycogen
• Oil red O stains for fat
• Vacuolar change in hepatocytes should prompt search for underlying disease or intoxication

Steroid Hepatopathy

• Occurs with Cushing's or exogenous corticosteroid administration
• Hepatocytes become swollen with glycogen
• Associated with marked increase in ALP (unique to dogs)
• Traditionally considered benign in dogs, but recent reports suggest it may be associated with hepatic remodeling and carcinoma
• Treatment involves removing the source of steroids or using antioxidants like SAMe

Glycogen-like Vacuolar Hepatopathy of the Scottish Terrier

• Characterized by marked increase in ALP and increased risk of hepatocellular carcinoma
• Nearly half of dogs present with clinical signs suggestive of hyperadrenocorticism, but adrenal testing can be negative
• Gallbladder mucocele reported in 16% of cases
• Coarse appearing liver with development of hypoechoic nodules indicative of hepatocyte death
• Affected dogs do not respond to treatment for Cushing's
• Treatment involves antioxidants, monitoring for masses with ultrasound

Hepatic Steatosis

• Accumulation of fat in hepatocytes
• Can occur with toxic injury (fatty degeneration)
• Can occur with primary or secondary disorders of fat metabolism
• Occurs with diabetes

Feline Hepatic Lipidosis

• > 50% of hepatocytes with cytoplasmic vacuoles consistent with lipid
• Obesity, anorexia, and stress are predisposing factors
• Primary form occurs in obese cats that have been anorexic for a period of time without an underlying disease
• Secondary hepatic lipidosis occurs in association with another disease (cholangitis, pancreatitis, IBD, diabetes, cancer)
• Cats with hepatic lipidosis have elevated circulating triglycerides and fatty acids, suggesting lipolysis of fat
• They also have higher beta-hydroxybutyrate levels, suggesting hepatic ketogenesis
• Diagnosis:
  • Moderate to marked increases in ALP and bilirubin
  • GGT is typically normal
  • Hypokalemia common due to prolonged anorexia and vomiting
  • Ultrasound shows hyperechoic hepatomegaly
  • Fine needle aspirate of the left side to avoid gallbladder
  • Careful with biopsies due to hepatic fracture and bleeding with coagulopathy
• Treatment:
  • Early intensive feeding is key, usually with tube feeding
  • Return to voluntary food intake often takes 12-16 days or longer
  • Offer high protein diet
  • Likely to require fluid support to correct hydration deficit
  • Supplementation with SAMe
  • Affected cats often have prolonged coagulation times that may normalize with vitamin K

Gallbladder Mucocele

• Cystic mucinous hyperplasia of the gallbladder wall with accumulation of thick mucous
• Associated with vacuolar hepatopathy

Superficial Necrolytic Dermatitis

• Hepatocutaneous syndrome
• Underlying pathogenesis involves amino acid deficiency
• Typical lesions are hyperkeratotic, erythematous, and ulcerated, often affecting foot pads and mucocutaneous junctions
• Lesions are painful
• Skin biopsies show parakeratotic hyperkeratosis with inter and intracellular edema
• Only ddx is zinc dermatosis
• US shows swiss cheese-like appearance of the liver
• Poor prognosis with death or euthanasia often within 6 months
• Treatment:
  • Parenteral amino acid infusion
  • High-quality, highly digestible, high-protein diet
  • Supplement extra zinc and fatty acids
  • Corticosteroids should be avoided

Hepatopathy Caused by Excessive or Abnormal Storage of Metal or Metabolite

• Excessive copper accumulation is an important cause of chronic hepatitis
• Iron overload: hemochromatosis
  • All cases in dogs are secondary, resulting from increased iron absorption in the intestine, abnormal iron excretion, or increased hepatic storage secondary to hemolysis
  • Reported in dogs with pyruvate kinase deficiency causing hemolytic anemia and repeated blood transfusions
  • Characterized by loading of Kupffer cells with hemosiderin, hepatocellular degeneration, and periportal fibrosis progressing to bridging fibrosis and cirrhosis

Alpha-1 Antitrypsin Deficiency

• Alpha-1 antitrypsin is a neutrophil elastase produced in the liver
• Intermediate form of the deficiency was most common in cocker spaniels with chronic hepatitis

Amyloidosis

• Accumulation of aggregated form of amyloid results in disease
• The most common generalized form of amyloidosis in dogs and cats is serum amyloid A (SAA) that occurs with inflammatory disease
• Feline hepatic amyloidosis:
  • Hepatic amyloidosis, with liver as primary site involved, occurs more commonly in cats
  • Siamese usually present with hepatic involvement, while Abyssinians usually present with renal disease
  • Usually young adults
  • Most often present due to bleeding from acute hepatic fracture of a friable liver
  • Jaundice and hepatomegaly
  • Marked elevations in liver enzymes and bilirubin
  • Diagnosis from liver biopsy
  • Treatment is supportive care and treatment for underlying inflammatory disease
• Canine hepatic amyloidosis:
  • Dogs suffer most from renal amyloidosis and most commonly present with PLN
  • The multi-organ disease that affects the Chinese Shar Pei can affect the liver, however. Affected Shar Peis are treated with colchicine.

Lysosomal Storage Diseases

• These diseases can cause vacuolation of hepatocytes but primary clinical manifestations are skeletal and neurologic