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Diagnosis of Liver Diseases
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The liver has many complex functions which is reflected in the multitude of pathophysiological derangements that can occur in liver disease. The liver has however a huge reserve capacity and great potential to regenerate, and clinical signs occur only when this reserve is exhausted by progressive disease.
Carolien RUTGERS
DVM, MS, Dipl ACVIM, Dipl ECVIM-CA, DSAM, MRCVS
Carolien graduated from Utrecht State University (Hons) with a DVM in 1985, and then completed an internship at the University of Pennsylvania and a residency and Masters degree at Ohio State University. She has worked in both general and referral small animal practice. She joined the University of Liverpool as a Lecturer in Small Animal Medicine In 1985 and moved to the Royal Veterinary College in 1990, where she became a Senior Lecturer. Carolien has published more than 100 scientific papers and book chapters, and has lectured widely in the UK and internationally. Her major research interest is in gastroenterology. She is a Diplomate of the American College of Veterinary Internal Medicine (ACVIM), a Founding Diplomate of the European College of Veterinary Internal Medicine - Companion Animals (ECVIM-CA), and a RCVS Diplomate in Small Animal Medicine (DSAM). Carolien has been a Board member of the ECVIM-CA and a member of the RCVS Small Animal Medicine and Surgery Board, and an Diploma examiner for both.
Vincent BIOURGE
DVM, PhD, Dipl ACVN Dipl ECVCN
Vincent Biourge graduated from the Faculty of Veterinary Medicine of the University of Liège (Belgium) in 1985. He stayed as an assistant in the nutrition department for 2 more years before moving to the Veterinary Hospital of University of Pennsylvania (Philadelphia, USA) and to the Veterinary Medical Teaching Hospital of the University of California (Davis, USA) as a PhD/resident in Clinical nutrition. In 1993, he was awarded his PhD in Nutrition from the University of California and became a Diplomate of the American College of Veterinary Nutrition (ACVN). In 1994, he joined the Research Center of Royal Canin in Aimargues (France) as head of scientific communication and nutritionist. Since 1999, he is in charge of managing the nutritional research program of Royal Canin. Dr. Biourge has published more than 30 papers, and regularly present scientific papers as well as guest lectures at International Veterinary Medicine and Nutrition meetings. He is also a Diplomate of the European College of Veterinary Comparative Nutrition (ECVN).
The liver is essential for the digestion, absorption, metabolism and storage of most nutrients (Table 1). Malnutrition is therefore common in liver disease, and the lack of nutrients can also aggravate it (Center, 1999b; Laflamme, 1999). Nutritional support is the keystone in the management of dogs with liver disease. It is therefore imperative to maintain nutrition status.
In acute liver disease, treatment is mainly aimed at supporting the patient during this process of hepatic regeneration, and patients may fully recover provided there has only been a single sublethal insult to the liver.
In chronic liver disease, the emphasis is on supporting the limited remaining metabolic capabilities of the liver, to minimize complications and to prevent progression of liver disease, e.g., by curtailing oxidative reactions. Early nutritional intervention in the management of malnutrition, ascites, and hepatic encephalopathy (HE) is especially important and can reduce morbidity and mortality.
Table 1. Major Hepatobiliary Functions | |
Protein Metabolism | Synthesis of albumin, acute phase proteins, coagulation factors Regulation of amino acid metabolism Detoxification of ammonia and synthesis of urea |
Carbohydrate Metabolism | Glycogen metabolism and storage Glucose homeostasis Gluconeogenesis |
Lipid Metabolism | Synthesis of triglycerides, phospholipids, cholesterol Lipid oxidation and ketone production Lipoprotein synthesis Excretion of cholesterol and bile acids |
Vitamin Metabolism | Storage and activation of vitamins B, K Activation of vitamin D Vitamin C synthesis |
Hormone Metabolism | Degradation of polypeptides and steroid hormones |
Storage Functions | Vitamins, lipids, glycogen, copper, iron, zinc |
Digestive Functions | Bile acid synthesis and enterohepatic circulation Digestion and absorption of lipids Absorption of vitamins A, D, E, K |
Detoxification and Excretion | Ammonia, drugs and toxins |
1. Diagnosis of Liver Diseases
History and Clinical Signs
Historical findings in dogs with liver disease are often vague and non-specific, and rarely evident until liver disease is advanced. The onset of clinical signs may be acute, even though this may be the end result of liver disease that has been progressing for many weeks or months.
Physical examination findings are often variable and non-specific. Jaundice, abnormal liver size and ascites are the findings most suggestive of liver disease, but these may also be seen in other diseases not related to the liver. The only sign specific for liver disease is acholic (grey) feces, which may be found in complete extrahepatic bile duct obstruction (Table 2).
Table 2. Clinical Findings in Liver Disease | |
Early signs | Anorexia Weight loss Lethargy Vomiting Diarrhea Polydipsia/polyuria |
Severe hepatic insufficiency | Jaundice Ascites Hepatic encephalopathy Coagulopathy (excessive bleeding upon blood sampling or liver biopsy, melena) |
Major bile duct obstruction | Acholic (pale) feces* |
* specific for liver disease, but rarely observed |
Differential Diagnosis
Jaundice
This is not a common sign of liver disease, and signifies severe disease. It may however also be due to hemolysis or post-hepatic causes (such as compression of the common bile duct, commonly seen in acute pancreatitis, or obstruction, due to neoplasia or cholelithiasis) (Leveille-Webster, 2000).
Altered Liver Size
In dogs, most chronic liver diseases result in reduced liver size, and even acute diseases may cause little change in size. Hepatomegaly is uncommon but may be seen in hepatic neoplasia and congestion, and with secondary involvement in metabolic disease (e.g., hyperadrenocorticism).
Ascites
This is a common occurrence in dogs with severe chronic liver disease, and is mostly caused by portal hypertension. It is a modified transudate, as also seen in congestive heart failure and neoplasia. It has to be distinguished from transudate, which may occur in protein-losing enteropathy and nephropathy, and from exudates, as in peritonitis, hemorrhage, and ruptured biliary or urinary tract.
Liver biopsy from a Bedlington Terrier with chronic hepatitis showing extensive copper accumulation (rhodanine stain; the copper grains show up as black). (© C. Rutgers).
Jaundice in a Doberman Pinscher with advanced chronic hepatitis. (© C. Rutgers).
Laboratory Testing
Laboratory assessment is essential to identify hepatic disease, assess severity and monitor progression; however, laboratory tests will not identify specific diseases and may be influenced by non-hepatic disease. Baseline tests (hematology, serum biochemistries and urinalysis) are useful in initial screening to look for evidence of hepatic disease as well as other abnormalities (Figure 1).
Figure 1. Diagnosis of liver disease.
Serum bile acid analysis is a sensitive and specific indicator of hepatic function, useful for the diagnosis of subclinical liver diseases and portosystemic shunts. Measurement of fasting serum ammonia can document the presence of HE. Coagulation tests are indicated in animals with a bleeding tendency and prior to biopsy (blind, ultrasoundguided or surgical) or a mesenteric portography if a portosystemic shunt is suspected.
Diagnostic Imaging
Survey abdominal radiographs provide an idea about liver size and shape, but ultrasonography gives more specific information about liver parenchyma, bile ducts and blood vessels. Operative mesenteric portography can visualize vascular anomalies; nuclear hepatic scintigraphy is non-invasive but requires specialized equipment and the use of radioactive tracers.
Biopsy
Histologic examination of liver tissue is often essential to clarify the cause of abnormal liver tests and/or size, to define whether it is a primary or secondary problem, and determine hepatic copper levels. It may also be used to monitor progression or response to treatment when non-invasive testing is inadequate.
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Affiliation of the authors at the time of publication
1Departement of Veterinary Clinical Sciences, The Royal Veterinary College, United Kingdom.2Royal Canin Research Center, France.
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