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Liver: chronic disease – overview
Introduction
- 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.
Presenting signs
- 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 presentation
- Acute-on-chronic inflammatory flare up or portal hypertension or end-stage liver failure.
Age predisposition
- 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.
Breed/Species predisposition
- 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).
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.
- Risk of hemorrhage during surgery including biopsy as coagulation times may be prolonged particularly in end stage disease.
Pathogenesis
Etiology
- 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.
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 → 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.
Timecourse
- >12 weeks of active illness.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed papers
- 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.