Contributors: Nick Bexfield, Penny Watson
Species: Canine | Classification: Diseases
Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading
- Includes: chronic hepatitis, copper associated hepatitis, drug induced hepatitis, lobular dissecting hepatitis, granulomatousidiopathic hepatitis, hepatic neoplasia, congenital abnormalities (ductal plate malformations including congenital hepatic fibrosis; portal vein hypoplasia).
- Cause: chronic hepatitis often idiopathic, some autoimmune, chronic infection, possible toxicity, neoplasia, congential malformation.
- Signs: may present as acute hepatitis with jaundice, ascites, or may be non-specific: lethargy, anorexia, vomiting, weight loss, signs of hepatic encephalopathy.
- Diagnosis: biochemistry, hepatic function tests, ultrasonography, definitive diagnosis requires hepatic biopsy.
- Treatment: elimination of cause if known, supportive and symptomatic measures, antibiotics or steroids or copper chelators as necessary.
- Prognosis: depends on underlying cause.
- Signs may be insidious and often wax and wane, or may be acute in onset when acute-on-chronic inflammatory flare up or development of portal hypertension resulting in ascites and hepatic encephalopathy, or reserve functional capacity is exceeded (approx >70%).
- Acute-on-chronic inflammatory flare up or portal hypertension or end-stage liver failure.
- Any age.
- Mean age for chronic hepatitis is 5-7 years. Usually <2 years of age in dogs with idiopathic hepatic fibrosis Liver: idiopathic fibrosis. Older for neoplasia.
- Standard Poodle Poodle: Standard.
- Bedlington Terrier Bedlington Terrier.
- Doberman Pinscher Dobermann.
- Skye Terrier Skye Terrier.
- West Highland White Terrier West Highland White Terrier.
- Cocker spaniel English Cocker Spaniel (American American Cocker Spaniel and English).
- Labrador Retriever Retriever: Labrador.
- Dalmatian Dalmatian.
- English Springer Spaniel English Springer Spaniel.
- German Shepherd German Shepherd Dog (idiopathic hepatic fibrosis).
- Long-term therapy can be expensive.
- Expenses incurred in establishing a diagnosis.
- Anesthesia as many commonly used drugs are metabolized in liver.
Warn owner of increased risk of anesthesia.
- Risk of hemorrhage during surgery including biopsy as coagulation times may be prolonged particularly in end stage disease.
- Idiopathic, chronic hepatitis.
- Autoimmune, chronic hepatitis.
- Copper accumulation: Bedlington terriers, Dalmatians, Dobermans, Labrador retrievers, West Highland White Terriers.
- Vascular disorders, eg congenital portosystemic shunts Congenital portosystemic shunt (CPSS) , portal vein hypoplasia and others Liver: congenital diseases.
- Drugs, eg anticonvulsants Therapeutics: nervous system, oxybendazole-diethylcarbamazine; carprofen Carprofen, acetoaminophen (paracetamol Paracetamol), potentiated sulphonamides.
- Infectious, eg leptospirosis Leptospirosis, acidophil cell hepatitis, bacterial endotoxemia, leishmania Leishmania infantum, histoplasma Histoplasma capsulatum, heterobilharzia americanum.
- Neoplasia, primary and secondary especially lymphoma Lymphoma.
- Lobular dissecting hepatitis Liver: lobular dissecting hepatitis (Standard Poodle).
- Congential ductal plate abnormalities including idiopathic hepatic fibrosis Liver: idiopathic fibrosis.
- 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 → sinusoidal fibrosis, contraction of myofibroblasts and periportal fibrosis → 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 → diarrhea → gastrointestinal ulceration → hematemesis and melena.
- Decreased production of clotting factors → bleeding tendency.
- Inflammation of biliary system and periportal inflammation and fibrosis → 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 results 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 distortion of the liver associated with regenerative nodules, it is termed cirrhosis Liver: cirrhosis.
- >12 weeks of active illness.
- Anorexia Anorexia.
- Vomiting Vomiting.
- Diarrhea Diarrhea: overview.
- Polydipsia/polyuria Polyuria/polydipsia (PU/PD).
- Abdominal enlargement.
- Signs of hepatic encephalopathy Hepatic encephalopathy.
- Decreased appetite.
- Unkempt hair/coat.
- Small liver on palpation.
- Poor bodily condition.
Signs of hepatic encephalopathy
- Behavioral changes: dementia, dullness, aggression, disorientation.
- Neurological abnormalities: circling, ataxia, head pressing, aimless pacing, seizures.
- Ptyalism (excessive salivation), unusual in dogs.
- ALT Blood biochemistry: alanine aminotransferase (SGPT, ALT), AST Blood biochemistry: aspartate aminotransferase (AST), ALP Blood biochemistry: alkaline phosphatase (ALP), GGT Blood biochemistry: gamma glutamyltransferase - abnormalities indicate liver disease or injury (not a measure of liver function).
Increased ALP is a sensitive but not specific indicator of cholestasis.
- Increased bilirubin Blood biochemistry: direct bilirubin (rule out hemolysis and post hepatic obstruction).
- Hypoalbuminemia Blood biochemistry: albumin.
- Reduced urea Blood biochemistry: urea.
- Reduced glucose Blood biochemistry: glucose (in most dogs glucose will only reduce with very advanced disease, and often is still in the normal range).
- Hypo or hypercholesterolemia Blood biochemistry: cholesterol.
- Bile acid stimulation testing Blood biochemistry: bile acids (supercedes BSP clearance test) for hepatobiliary function and portosystemic shunts. Elevation usually indicated portsystemic shunting. Also elevated in cholestasis so cannot be interpreted if bilirubin is also high.
- Ammonia Blood biochemistry: ammonia for hepatobiliary function and portosystemic shunts.
- Non-regenerative often microcytic anemia Anemia: non-regenerative.
- Presence of target cells.
- Also to check gastrointestinal bleeding and hemolytic disease as a cause of the jaundice.
Exclude systemic causes of enzyme elevation before undertaking invasive diagnostic procedures.
- Fine needle aspiration Fine-needle aspirate. Very limited use except for the diagnosis of lymphoma Lymphoma or amyloidosis Amyloidosis.
- Percutaneous-blind Biopsy: hepatic or ultrasound-guided needle biopsy Biopsy: ultrasound-guided. Can be misleading - wedge biopsy preferred.
- Laparoscopy-guided biopsy. Preferred.
- Laparotomy Laparotomy: midline. Also preferred.
Check for possible coagulopathy Anticoagulant rodenticide poisoning before biopsy.
- See Ultrasonography: liver.
- Doppler ultrasound - portosystemic shunt.
- Evaluate parenchyma and biliary system .
- 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
- See Radiology: liver.
- Small (microhepatica): portosystemic shunt, hepatic cirrhosis Liver: cirrhosis, hepatic fibrosis.
- Liver size can be normal Radiography: abdomen.
- Focal masses.
- Multifocal radiolucencies - infection or abscessation.
- Contrast study: surgically expose and inject iodine contrast media into portal vein to identify portosystemic shunt. Superceded now by CT Computed tomography.
- Congenital portosystemic shunts Computed tomography: angiography .
Gross Autopsy Findings
- Swollen, pale, nodular liver.
- Shrunken liver late in disease process.
- Variable-sized regenerative nodules.
- Focal/multifocal masses.
- Varies with cause, eg:
- Chronic hepatitis, 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.
- Congenital ductal plate abnormalities: biliary cysts; abnormal portal triads with multiple small bile ducts and fibrosis.
- Presence of specific neoplastic cells, especially metastatic.
Primary liver diseases
- Chronic hepatitis Liver: chronic hepatitis.
- Neoplasia Liver: neoplasia.
- Portosystemic shunts Congenital portosystemic shunt (CPSS).
- Toxic hepatopathy (see Liver: acute disease ).
Secondary liver diseases
- Neoplasia - metastatic.
- Metabolic disease (hyperadrenocorticism Hyperadrenocorticism, hypothyroidism, diabetes mellitus Diabetes mellitus).
Causes of jaundice
- Causes of hemolytic anemia Anemia: immune mediated hemolytic.
- Hepatocellular disease (see primary and systemic causes of liver disease).
- Biliary disease Biliary system: disease (cholestatic disease): infection, gall bladder mucocele, neoplasia.
- Biliary tract obstruction: intrahepatic, eg neoplasia, inflammation; extrahepatic, eg chronic pancreatitis, pancreatic neoplasia or inflammation, gall stones (choleliths).
Causes of ascites
- Advanced hepatic disease.
- Abdominal neoplasia.
- Right-sided congestive heart failure Heart: congestive heart failure.
- Chylous ascites.
- Bacterial peritonitis Peritonitis.
- Other fluids (hemorrhage, bladder or biliary rupture).
Initial Symptomatic Treatment
- Intravenous fluids if acute worsening.
- Sucralfate Sucralfate and omeprazole Omeprazole or an H2 blocker if gastrointestinal bleeding.
Cimetidine 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 adding 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 and low copper diet Dietetic diet: for liver insufficiency.
- Moderately low protein restricted 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 if suspected autoimmune chronic hepatitis. A sensible starting dose would be 1 mg/kg SID then gradually reducing the dose and frequency of dosing.
- Their use in end-stage fibrosis and cirrhosis is unhelpful and may worsen gastrointestinal ulceration, increase protein catabolism and fluid retention.
- Cyclosporine Ciclosporin and alternative to steroids in suspected autoimmune chronic hepatitis and less likely to cause side effects in end stage fibrosis.
- Antifibrosing drugs, eg colchicine Colchicine. Not recommended - no good evidence of efficacy.
- Repeat hepatic function tests and hepatic biopsy.
- Measure body weight, body condition score and blood albumin Blood biochemistry: albumin to assess the need for dietary supplementation with additional protein.
- Depends on underlying cause and degree of hepatic damage.
- Generally guarded to poor prognosis in chronic hepatitis. Prognosis poorer if ascites present or jaundiced.
- Prognosis can be good in copper associated chronic hepatitis if effectively chelated.
- Congenital ductal plate abnormalities and portal vein hypoplasia can have a good prognosis with supportive care.
Expected Response to Treatment
- Clinical improvement.
- Resolution of hepatic pathology.
Reasons for Treatment Failure
- Development of hepatic cirrhosis.
- End stage liver failure with loss of >70% hepatocyte mass
- Recent references from PubMed and PubMed.
- Webster C R L, Center S A, Cullen J M et al (2019) ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs. J Vet Intern Med 33 (3), 1173-1200 PubMed.
- Bexfield N H, Buxton R J, Vicek T J et al (2012) Breed, age and gender distribution of dogs with chronic hepatitis in the United Kingdom. Vet J 193 (1), 124-128 PubMed.
- Poldervaart R P et al (2009) Primary hepatitis in dogs: a retrospective review (2002 –2006). J Vet Intern Med 23 (1): 72-80 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.
- 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
- Lidbury (2023) Chronic Hepatitis. In: Textbook of Veterinary Internal Medicine. 9th edn. Eds: S J Ettinger, E C Feldman & Coté E. W B Saunders, USA.
- 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, UK. pp 240-268.