Contributors: Nick Bexfield

 Species: Canine   |   Classification: Diseases

Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading

Introduction

  • Includes: chronic active hepatitis, copper associated hepatitis, drug induced hepatitis, lobular dissecting hepatitis, idiopathic hepatitis.
  • Cause: malformation, toxicity, neoplasia, endocrinopathy, infection.
  • Signs: may present as acute hepatitis, or may be non-specific: lethargy, anorexia, vomiting. Signs of hepatic encephalopathy.
  • Diagnosis: biochemistry, hepatic function tests, ultrasonography, ultimately hepatic biopsy.
  • Treatment: elimination of cause if known, supportive and symptomatic measures.
  • Prognosis: depends on underlying cause.

Presenting Signs

  • Signs may be insidious or may be acute in onset when reserve functional capacity is exceeded (>70%).

Acute Presentation

  • End-stage liver failure.

Age Predisposition

  • Any age, although mean age is 5-7 years. Usually <2 years of age in dogs with idiopathic hepatic fibrosis Liver: idiopathic fibrosis.

Breed Predisposition

Cost Considerations

  • Long-term therapy can be expensive.
  • Expenses incurred in establishing a diagnosis.

Special Risks

  • Anesthesia as many commonly used drugs are metabolized in liver.
    Warn owner of increased risk of anesthesia.

Pathogenesis

Etiology

Pathophysiology

  • Cumulative hepatic insult → functional reserve capacity exceeded (>70% damage) → failure to perform diverse metabolic functions → clinical signs.
  • Increased resistance to blood flow through liver due to hepatocytes swelling → development of portal hypertension →ascites. Ascites may also develop due to hypoalbuminemia Hypoproteinemia.
  • Acquired shunting vessels may develop due to sustained portal hypertension.
  • Failure to detoxify ammonia from intestine due to reduced hepatic mass and presence of acquired shunting vessels → hepatic encephalopathy Hepatic encephalopathy.
  • Portal hypertension → gastrointestinal wall congestion and edema → gastrointestinal ulceration → hematemesis and melena.
  • Inadequate bile delivery to intestine → impairment of fat digestion → diarrhea.
  • Decreased production of clotting factors →bleeding tendency.
  • Inflammation of biliary system → partial obstruction to biliary flow →icterus.
  • Decreased production of urea in the urea cycle → reduced blood urea.
  • Decreased production of albumin →hypoalbuminemia.
  • Chronic liver disease may result in fibrosis. If the injury is severe and/or ongoing, the liver will respond by laying down fibrous tissue. This represents a final common pathway to a variety of insults to the liver.
  • When bridging fibrosis causes permanent distortion of the liver associated with regenerative nodules, it is termed cirrhosis Liver: cirrhosis.

Timecourse

  • >12 weeks of active illness.

Diagnosis

Client History

  • Anorexia.
  • Depression.
  • Vomiting.
  • Diarrhea.
  • Polydipsia/polyuria.
  • Jaundice.
  • Abdominal enlargement.
  • Signs of hepatic encephalopathy Hepatic encephalopathy.

Clinical Signs

  • Lethargy.
  • Decreased appetite.
  • Vomiting.
  • Diarrhea.
  • Polydipsia/polyuria.
  • Unkempt hair/coat.
  • Jaundice.
  • Small liver on palpation.
  • Poor bodily condition.
  • Ascites.

Signs of hepatic encephalopathy

  • Behavioral changes - dementia, dullness, aggression, disorientation.
  • Neurological abnormalities - circling, ataxia, head pressing, aimless pacing, seizures.
  • Ptyalism (excessive salivation).
  • Coma.

Diagnostic Investigation


Biochemistry

Hematology

  • Non-regenerative anemia Anemia: non-regenerative.
  • Presence of target cells.
  • Also to check for hemolytic disease as a cause of the jaundice.

Histopathology

Exclude systemic causes of enzyme elevation before undertaking invasive diagnostic procedures.


2-D Ultrasonography
  • See Ultrasonography: liver Ultrasonography: liver.
  • Doppler ultrasound - portosystemic shunt.
  • Evaluate parenchyma and biliary system Liver normal vessels - ultrasound.
  • Identify focal lesions.
  • Guide needle biopsy.
    If there is no dilation of the extrahepatic biliary tract, and no hemolytic disease in the presence of jaundice, hepatocellular disease is likely → do liver biopsy
  • Diffuse echogenicity - hepatic lipidosis, hepatic cirrhosis.

Radiography
  • See Radiology: liver Radiology: liver.
  • Small (microhepatica) - portosystemic shunt, hepatic cirrhosis Liver: cirrhosis , hepatic fibrosis.
  • Liver size can be normal Radiography: abdomen.
  • Hepatomegaly.
  • Focal masses.
  • Multifocal radiolucencies - infection or abscessation.
  • Contrast study: surgically expose and inject iodine contrast media into portal vein to identify portosystemic shunt.

Gross Autopsy Findings

  • Swollen, pale, nodular liver.
  • Shrunken liver late in disease process.
  • Variable-sized regenerative nodules.
  • Focal/multifocal masses.

Histopathology Findings

  • Varies with cause, eg:
    • Moderate to severe inflammation associated with 'piece-meal' necrosis of hepatocytes; begins in portal triad and extends into parenchyma.
    • Small islands of hepatocytes surrounded by inflammatory cells (lymphocytes, plasma cells, sometimes neutrophils) → bridging necrosis → active cirrhosis.
    • Special stains for copper accumulation (Rubeanic acid, Rhodamine).
    • Fibrosis and parenchymal nodules that disrupt normal hepatic architecture.
    • Presence of specific neoplastic cells, especially metastatic.

Differential Diagnosis


Primary liver diseasesSecondary liver diseasesCauses of jaundice
  • Causes of hemolytic anemia Anemia: immune mediated hemolytic.
  • Hepatocellular disease (see primary and systemic causes of liver disease).
  • Obstructive: intrahepatic, eg neoplasia, inflammation; extrahepatic, eg pancreatic neoplasia Pancreas pancreatitis or neoplasia - radiograph or inflammation, bile stones.
Causes of ascites
  • Advanced hepatic disease.
  • Hypoalbuminemia.
  • Abdominal neoplasia.
  • Right-sided congestive heart failure Heart: congestive heart failure.
  • Chylous ascites.
  • Bacterial peritonitis Peritonitis.
  • Other fluids (hemorrhage, bladder or biliary rupture).

Treatment

Initial Symptomatic Treatment

  • Intravenous fluids if acute worsening.
  • Sucralfate Sucralfate and an H2 blocker if gastrointestinal bleeding.
    Cimetidine decreases liver P450 enzymes → alterations in metabolism of many drugs. Use other H2 blocking drugs first, eg ranitidine Ranitidine.
  • Spironolactone Spironolactone if ascites; if refractory, try furosemide Furosemide.
  • Ampicillin Ampicillin and lactulose Lactulose if evidence of hepatic encephalopathy.
  • Ursodeoxycholic acid Ursodeoxycholic acid to stimulate bile flow, displace toxic bile acids, and modulate immune response.
  • Anti-oxidants such as SAMe S-adenosylmethionine , silybin/silymarin (milk thistle) Silybin or vitamin E Vitamin E. SAMe, which increases blood glutathione levels, is widely available as are silybin/silymarin and vitamin E. Research has shown the combination of SAMe and silybin to be complementary in attenuating inflammation in canine hepatocytes.
  • D-penicillamine Penicillamine or 2,2,2-tetramine for copper chelation.
  • Low protein diet Dietetic diet: for liver insufficiency only necessary if evidence of encephalopathy. If no encephalopathy, diet should contain sufficient high quality protein to allow the liver to regenerate. If feeding a prescription diet formulated for dogs with hepatic disease, these should always be supplemented with a source of high quality protein such as cottage cheese.
  • Excessive protein restriction will lead to muscle catabolism and worsening of HE.
  • Steroids are very effective antifibrotics, but should only be used if there is an inflammatory infiltrate. Their use in end-stage fibrosis and cirrhosis is unhelpful and may worsen gastrointestinal ulceration, increase protein catabolism and fluid retention.
  • Few if any dogs have autoimmune hepatitis, so the use of immunosuppressive doses of steroids (2-4 mg/kg SID) is not recommended. A sensible starting dose would be 1 mg/kg SID then gradually reducing the dose and frequency of dosing.
  • Antifibrosing drugs, eg colchicine Colchicine. Recent studies in humans have questioned its effectiveness.
    Studies in dogs are lacking so there is little current evidence to support its use.

Subsequent Management

Treatment

  • Repeat hepatic function tests and hepatic biopsy.
  • Measure blood albumin Blood biochemistry: albumin to assess the need for dietary supplementation with additional protein.

Outcomes

Prognosis

  • Depends on underlying cause and degree of hepatic damage.
  • Generally poor diagnosis.
  • Prognosis much poorer if ascites present.

Expected Response to Treatment

  • Clinical improvement.
  • Resolution of hepatic pathology.

Reasons for Treatment Failure

  • Development of hepatic cirrhosis.

Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Au A Y, Hasenwinkel J M, Frondoza C G (2013) Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytes in vitro. J Anim Physiol Anim Nutr (Berl) 97 (2), 331-41 PubMed.
  • Mandigers P J, van den Ingh T S, Spee B, Penning L C, Bode P, Rothuizen J (2004) Chronic hepatitis in Doberman pinschers. A review. Vet Q 26 (3), 98-106 PubMed.
  • Watson P J (2004) Chronic hepatitis in dogs: a review of current understanding of the aetiology, progression and treatment. Vet J 167 (3), 228-241 PubMed.
  • Center S A (1999) Chronic liver disease: current concepts of disease mechanisms. JSAP 40 (3), 106-114 PubMed.
  • Sevelius E (1995) Diagnosis and prognosis of chronic hepatitis and cirrhosis in dogs. JSAP 36 (12), 521-528 PubMed.
  • Andersson M, Sevelius E (1991) Breed, sex and age distribution in dogs with chronic liver disease: a demographic study. JSAP 32 (1), 1-5 VetMedResource.

Other sources of information

  • Watson P J (2005) Diseases of the liver. In: BSAVA Manual of Canine and Feline Gastroenterology. 2nd edn. Eds: E J Hall, J W Simpson & D A Williams. BSAVA Publications. pp 240-268.
  • Willard M D (2005) Inflammatory canine hepatic disorders. In:T extbook of Veterinary Internal Medicine. 6th edn. Eds: S J Ettinger & E C Feldman. W B Saunders, Philadelphia. pp 1442-1447.

Other Sources of Information