7 Equine Liver Disease NOTES

Equine Liver Disease

• Biochemical tests are important to evaluate liver disease and function in horses.

Hepatic Insufficiency and Failure

• The liver has high regenerative capabilities.
• Most hepatic functions remain unimpaired until the loss of over 80% of hepatic mass.
• Liver disease can occur without leading to liver failure.
• Hepatic disease does not always show clinical signs, but can be found by lab tests.

Clinical Signs of Hepatic Disease

• Often nonspecific, including anorexia, depression, mild colic, icterus, weight loss, and fever.
• Progression to failure causes hepatic encephalopathy (HE), photosensitization, bilateral laryngeal paralysis, and bleeding.

Clinical Signs of Hepatic Encephalopathy (HE)

• Excessive yawning, altered mentation, stupor, unawareness, head pressing, aimless walking, unconsciousness, and recumbency.

Diagnosis of Liver Disease

• Largely based on clinical chemistry.
• Hyperbilirubinemia is not very specific and rises occur due to liver disease, hemolysis, and anorexia.
• Indirect (unconjugated) bilirubin elevates with all three issues.
• Direct (conjugated) bilirubin elevation can indicate liver disease, but is not always present.
• Elevated direct bilirubin, greater than 30% of total bilirubin, indicates a post-hepatic issue like cholelithiasis.

Liver Enzymes

• Four common enzymes are assessed - two hepatocellular and two biliary.
• All four enzymes increase with either hepatocellular or biliary disease.
• Sorbitol dehydrogenase (SDH) is a hepatocellular specific enzyme.
  • SDH is very sensitive with a short half-life.
  • Interpretation is difficult if analysis is delayed.
• Aspartate aminotransferase (AST) is found in hepatocytes and muscle cells, making it non-specific.
  • With elevations, always evaluate CK.
  • ALT is not useful in LA.
• Alkaline phosphatase (ALP) is a non-specific enzyme, but usually increases with biliary diseases.
  • Other sources are bone, intestine, kidney, placenta, and leukocytes.
• Gamma-glutamyl transpeptidase (GGT) is a specific biliary enzyme.
  • GGT has a long half-life.
  • Many clinicians find GGT very useful.

Serum Bile Acids

• Bile acids are an indicator of liver function replacing foreign dye clearances.
• Horses do not typically need to be fasted for bile acid measurements.
• Increases in bile acids occur with liver and cholestatic disease, with larger increases in cholestatic disease.

Albumin

• Hypoalbuminemia is uncommon in horses due to the long half-life of albumin compared to other species.
• Decreases can be seen in end-stage liver disease.

Blood Urea Nitrogen (BUN)

• BUN concentrations decrease with significant liver disease and failure.

Blood Ammonia Concentrations

• Blood ammonia increases with liver disease or failure.
• High ammonia is often seen with hepatoencephalopathy.
• measuring ammonia is expensive.

Coagulation Factors

• Changes in hemostasis can occur with significant liver disease or failure.

Ultrasound

• Ultrasound and liver biopsy are commonly used.
• Ultrasounds can find dilated bile ducts or obstructions, abscesses, cysts, or neoplasia.
• Ultrasound-guided liver biopsies are used for histology or culture.
• Evaluations of hemostasis (OSPT, APTT) are typically done prior to biopsy.

General Liver Disease Treatment

• Treatment is often supportive.

• Fluid therapy depends on severity of disease.

  • Electrolyte, acid-base and hypoglycemia are common in severe cases.

• Anti-inflammatory drugs like NSAIDs (flunixin), DMSO, and pentoxifylline are used.

• Nutrition includes small, frequent feedings of easily digestible carbohydrates, like grain or equine senior with lower protein.

  • Eating carbohydrates is important (alfalfa hay is a good source, but is high in protein).

• Drugs to decrease fibrosis include pentoxifylline and colchicine.

• Drugs to reduce ammonia in the GIT (or reduce absorption) are mineral oil, neomycin, and lactulose, although these can cause diarrhea.

• Antibiotics are commonly used due to concerns about bacterial cholangiohepatitis.

• Equine liver disease is not uncommon, but the exact cause often remains unknown even with thorough diagnostics.

• Treatment is largely supportive, with antibiotics used even without evidence of bacterial infections.

Equine Hyperlipemia

• Hyperlipemia is a condition affecting miniature horses, donkeys, and ponies with negative energy balance.
• Horses develop hypertriglyceridemia and hepatic lipidosis, but not ketosis.

Definitions for Equine Hyperlipemia

• Hypertriglyceridemia means elevated serum triglyceride concentrations.
• Hyperlipidemia describes an increase in serum triglyceride concentration above normal, generally less than 500 mg/dl, without visible lipemia of plasma.
  • This also occurs without evidence of fat infiltration of body tissues or organs.
• Hyperlipemia is an increase in serum triglyceride concentrations, usually greater than 500 mg/dl, along with gross lipemia of the plasma and fat infiltration of body tissues/organs.
• Severe hypertriglyceridemia in normal-sized horses shows triglyceride concentrations higher than 500 mg/dl with fat infiltration into organs not typically reported.

Signalment and Clinical Signs of Hyperlipemia

• Commonly affects miniature horses, ponies, and donkeys, especially females and obese animals.
• History of negative energy balance includes late gestation, lactating mares, heavy parasite load, and any disease resulting in anorexia.
• Non-specific clinical signs feature depression, anorexia, weakness, and decreased fecal production. Progression results in hepatic lipidosis and liver failure.
  • Clinical signs of hepatic lipidosis include colic from stretching of the liver capsule and hepatoencephalopathy.
  • abortion and renal failure can occur in pregnant mares.

Normal Triglyceride Metabolism

• During negative energy balance, triglycerides undergo lipolysis in adipocytes via hormone-sensitive lipase, releasing free fatty acids (FFA) and glycerol into circulation.
• FFA in the liver can be oxidized for energy via acetyl CoA, partially oxidized for ketone production and re-esterified to produce triglycerides.
  • Ketone production is poorly developed in the horse.
  • The liver releases triglycerides into circulation as very-low-density-lipoproteins (VLDL).
• Peripheral tissues release FFA from VLDL via lipoprotein lipase and use it for energy.
• Hyperlipemia results from negative energy balance, increasing hormone-sensitive lipase activity where released FFA exceeds the liver's oxidative capacity.
• FFA are re-esterified into triglycerides then released back as VLDL, overwhelming peripheral tissues.
• Hepatic lipidosis results when VLDL release overwhelms peripheral tissue uptake, leading to liver disease, liver failure, or liver rupture.
• Hyperlipemia is not due to the reduced ability to clear VLDL, but the overproduction of triglycerides and VLDL from the liver.
• Ponies and minis have a different VLDL type caused by a different apolipoprotein in the VLDL (apolipoprotein B-48) which results in greater triglyceride concentrations.
• A diagnosis of hyperlipemia is suspected based on signalment and history of negative energy balance, and clinical signs.
  • A preliminary diagnosis shows opaque plasma and a confirmed diagnosis includes lipemic serum/plasma, triglyceride concentrations higher than 500 mg/dL, and evidence of organ dysfunction.
• Hyperlipidemia is also commonly diagnosed where horses displaying the signs should be monitored.
• Normal triglyceride concentrations in adult horses/ponies are less than 85 mg/dl.
• Normal triglyceride concentrations are up to 290 mg/dl in donkeys and 250 mg/dl in pregnant ponies.

Treatment Aims

• Increase caloric intake, treat underlying disease, decrease fat mobilization from adipose tissue while increasing triglyceride uptake.

• Increasing caloric intake includes frequent offerings of highly palatable food like green grass or concentrated carbohydrates.

  • Other methods include assisted enteral feeding using a nasogastric tube with water-soaked pellets or commercial powdered formulas, and total or partial parenteral nutrition.

• Treat underlying disease and negative energy balance, such as weaning the foal if lactating or terminating pregnancy if pregnant and resolving underlying issues speeds up recovery.

• Decreasing fat mobilization and increasing triglyceride uptake can be done but with some caveats.

• Heparin increases lipoprotein lipase activity, but activity is already increased with hyperlipemia not due to decreased triglyceride uptake.

• Insulin, with concurrent dextrose administration, has an antagonistic effect on lipolysis but carries a hypoglycemia risk when using parenteral nutrition.

Theiler’s Disease

• Theiler’s Disease is serum sickness, acute hepatic necrosis, or serum-associated hepatitis with recent reports showing equine parvovirus-hepatitis contamination of biological products.

• Its development is associated with the administration of biological products to horses weeks to months after administration often caused by tetanus antitoxin.

• It affects adult horses.

• Clinical signs include liver that often progress to liver failure.

• Diagnosis consists of history of biologics, blood work and clinical signs supportive of the diagnosis, and by widespread centrolobular to midzonal hepatocellular necrosis with hemorrhage.

• Treatment is supportive with a poor prognosis and signs of liver failure.

Tyzzer’s Disease

• Is a bacterial infection of the liver is caused by Clostridium piliformis
• This infection effects foals from 7 to 42 days with outbreaks that have been reported
• Clinical signs feature liver disease that progresses to liver failure and dead foals are common.
• Diagnosis considers liver disease in foals, confirmed by necropsy or biopsy with sliver stain for C. piliformis. A PCR test is available but difficult to culture
• Treatment with penicillin and supportive care is highly fatal.
• Transmission occurs when foals ingest C. piliformis from feces or soil and the bacteria replicate in the intestinal epithelium that spread to the liver.

Other Bacterial Infections

• Other Bacterial Infections most likely include bacterial cholangiohepatitis, which can ascend into the liver and is typically caused by enterocolitis and intestinal obstruction.
• Primary bacterial hepatitis is rare.
• These occur in adult horses with or without a history of gastrointestinal disease where it is less common to see evidence of liver failure.
• Diagnosis is based on liver biopsy, and treatment is provided with antimicrobial drugs usually based on culture and sensitivity.

Toxic Hepatopathy

• Toxic Hepatopathy is caused by plants, chemicals, drugs, and mycotoxins, where clinical signs and tests do not distinguish them except for pyrrolizidine alkaloid toxicity confirmed by liver biopsy.
• Diagnosis requires identifying the toxin.
• Plants include kleingrass, lecheguilla, sneezeweed, blue-green algae, rye grass and mushrooms and exposure usually causes chronic hepatitis and fibrosis.

Pyrrolizidine Alkaloid

• Pyrrolizidine alkaloid toxicity causes megalocytic hepatopathy, common in chronic liver disease in parts of the US, often caused by Senecio spp, Amsinckia spp, Crotalaria spp and Heliotropium spp.
• These plants are unpalatable, but horses consume them if other forage is lacking.
• The effects of the toxins are cumulative, and toxicity develops due to lack of other forage following chronic low-level exposure such as ingesting pyrrolizidine alkaloids which metabolize into toxic pyrrole derivatives causing the cells to enlarge.
• Pyrroles inhibit cellular replication and protein synthesis, preventing cell division, resulting in megalocytosis. When these megalocytes die, fibrosis develops.
• Clinical signs develop 4-12 weeks after consumption that often progresses to liver failure.
• Diagnosis includes a history of exposure and clinical signs, with liver biopsy (megalocytosis, biliary hyperplasia, and fibrosis).
• There is no specific treatment.
• Mycotoxins are potentially hepatotoxic, with Fumonisin B1 causing moldy corn poisoning that can cause hepatic disease.

Cholelithiasis

• Cholelithiasis, or biliary calculi, commonly affect adult, middle-aged horses and is signaled by clinical signs of liver disease that typically doesn't progress to liver failure, but colic and fever do occur.
• Most choleliths in horses consist of calcium bilirubinate and are associated with bacterial cholangitis due to unknown sequences.
• Diagnosis includes blood work elevations in GGT and bile acids, and often diagnosis by ultrasound shows dilated bile ducts, and hyper foci in bile ducts.
• Treatment most commonly includes long-term antibiotics and supportive medical care although surgery may be required in limited cases with mixed success.
• The prognosis depends on extent of hepatic fibrosis, and size of the choleliths.