Discussion

Toxic causes of liver failure in horses include pyrrolizidine alkaloid toxicosis (e.g. Senecio spp., Amsinckia spp.), alsike clover, Panicum grasses (Kleingrass, fall Panicum). Although iron has frequently been blamed as a toxic cause of liver failure in horses, it is not well documented in adult horses and mycotoxins rarely cause liver failure. Blood transfusions and iron overload have been associated with liver failure in foals. Infectious causes include cholangiohepatitis, Theiler's disease in adult horses and Tyzzer's disease in 6 - 42 day old foals. Actinobacillus, EHV1, Streptococcus zooepidemicus and Leptospira are rare causes of liver failure in neonatal foals. Inflammatory, noninfectious causes include chronic active hepatitis, neoplasia, granulomatous (disease), drug- induced (especially in foals). Hepatic lipidosis (in ponies and miniature horses) is the predominant metabolic cause although hyperammoninaemia can occur in Morgan foals. Obstructive causes include biliary stones, neoplasia, right dorsal colon displacements, and rarely papillary stricture (foals with duodenal ulcers). Miscellaneous causes include hepatic torsion, portal vein thrombosis and porto-systemic shunts.
The clinical signs of liver failure can vary depending most upon duration (acute or chronic), predominant biliary vs. hepatocellular injury, and specific causes. Horses with acute liver failure are more likely to have central nervous system signs as their initial and predominant sign. Horses with chronic liver disease leading to failure commonly (but not always) have weight loss and/or photosensitivity as a clinical finding. Gastric impaction and bilateral laryngeal paralysis are 2 of many complications that may be seen with equine hepatic failure. Horses with liver disease that is most pronounced in the biliary system are often more jaundiced, more likely to be colicky (due to biliary obstruction and possibly an enlarged liver), have photosensitivity and less likely to have CNS signs. Specific causes of liver failure can also result in more specific findings; these include fever with cholangiohepatitis, ventral oedema with hepatic lipidosis, and abdominal distention with right displacement of the colon causing biliary obstruction.
Biochemical testing is imperative in the diagnosis of both liver disease and liver failure. Biochemical results can be helpful in narrowing the differential diagnosis for the liver failure and, when evaluated over time, can help predict prognosis. Liver specific enzymes include sorbital dehydrogenase (SDH) and gamma glutamyltransferase (GGT) which respectively reflect hepatocellular and biliary injury. Aspartate aminotransferase (AST) and alkaline phosphatase (AP) also respectively reflect hepatocellular and biliary injury, but are not liver specific. Sorbital dehydrogenase and glutamate lactate dehydrogenase have a short half-life which can be very helpful in determining resolution or progression of the hepatic insult. GGT is released mostly from biliary epithelium and, in the horse, often continues to elevate for a few days (presumably due to biliary hyperplasia) after the hepatic insult is no longer present. HCT and serum iron are frequently high in horses with severe liver disease. Racehorses may rarely have mild increases (50 - 140 iu/l) in GGT without any other evidence of liver disease.
Liver function tests only become abnormal when approximately 60 - 70% of liver function is lost and these tests include elevations in direct bilirubin, blood ammonia, prothrombin and partial thromboplastin time, and gamma globulins (with chronic disease). An increase in direct bilirubin of more than 0.2 mg/dl above normal maximum is a highly sensitive and specific marker of liver failure in equines greater than 3 months of age. When the increase in direct bilirubin is 25% or more of the total bilirubin, this is suggestive of a predominant biliary disease. Septic foals and rarely adult horses (grass sickness) with intestinal ileus sometimes have elevations in direct bilirubin with minimal evidence of hepatic dysfunction. This may be due to biliary stasis or resorption of the bilirubin from the intestinal tract. There may be a decrease in BUN and albumin (with chronic diseases). Serum or plasma bile acids can be an early predictor of liver failure when values rise above 30 umol/l in equines >2 months of age. Serum triglycerides are markedly increased in equines with hepatic lipidosis. In foals with hepatic failure, hypoglycaemia is often present, while in adult horses, blood glucose is generally normal or increased.
Ultrasound examination and liver biopsy are the 2 most commonly used ancillary tests for detecting liver disease. Ultrasound examination may reveal dilated bile ducts, biliary sludge, biliary stones, hepatic fibrosis, hepatomegaly, smaller than normal liver (very subjective), hepatic lipidosis and hepatic masses. Liver biopsy is best performed after the liver has been visualised on ultrasound examination on either the right or left side. Liver biopsies are best used to determine amount of fibrosis, inflammation, predominant location of disease and for culture purposes.
Treatments of liver failure or liver disease will vary depending on cause. Supportive treatments for most cases of equine liver failure include crystalloid therapy with supplemental dextrose and potassium. If hepatoencephalopathy is a concern, a low protein (high branch chain-low aromatic amino acid ratio) diet should be fed and neomycin and/or lactulose should be given per os (via syringe) to decrease enteric ammonia production. Feeds containing carbohydrates and branch chain amino acid should be given every 2 - 4 h if the animals are still eating. Horses with maniacal behaviour due to hepatoencephalopathy can be sedated with small amounts of a2 agonist such that the horse's abnormal behaviour is controlled yet maintaining the head in a normal position to prevent worsening of possible cerebral oedema. Mannitol can be used for suspected brain oedema in fulminant hepatoencephalopathy although cerebral oedema in equine hepatoencephalopathy as it is in humans? Horses with hepatic disease should be protected from sunlight. Pentoxyfilline should be administered for inflammatory and/or fibrosing liver diseases. S-adenosylmethionine (SAMe) (5 g per os s.i.d.) can be administered if oxidative injury is suspected, although the importance of crushing the coated tablet prior to administration is unknown. Intravenously administered acetylcystein has been routinely used with acute fulminant disease in humans, but its value in treating equine hepatic diseases is also unknown. Antibiotics should be administered if septic cholangiohepatitis is the diagnosis. Intravenous penicillin (or ampicillin), gentamicin and metronidazole are reasonable choices as is enrofloxacin and metronidazole. Depending upon culture and sensitivity, trimethoprim sulfa may be appropriate for long-term treatment. If there is a physical obstruction of the biliary duct, e.g. cholelith or obstruction caused by right colon displacement, surgery may be indicated. For chronic active hepatitis, pentoxifylline (7.5 mg/kg bwt per os q. 12 h), SAMe, colchicine (0.03 mg/kg bwt per os q. 24 h) and steroids (dexamethasone 0.05 - 0.1 mg/kg bwt i.m. or prednisolone 0.5 - 1.0 mg/kg bwt per os q. 24 h) are used. Ursodeoxycholic acid (15 mg/kg bwt per os q. 24 h) has been used with clinical success in several horses with cholangiohepatitis or chronic active hepatitis. Hepatic lipidosis treatments are: treat the predisposing disorder, fluids including dextrose and potassium, enteral nutrition if possible and regular insulin (0.1 - 1.0 iu/kg bwt) (or 0.4 iu/kg bwt q. 24 h protamine Zn insulin) as needed for hyperglycaemia.
Prognosis is variable depending upon cause! Theiler's disease horses are usually either dead or markedly improved within 3 - 5 days. Treatment response for CAH is variable and responding cases should be treated until the GGT is normal. Cholangiohepatitis cases often have a good prognosis if medical treatment has some positive effect within 7 - 10 days, there is not severe fibrosis, and large obstructing stones are not seen on ultrasound examination. Toxic causes such as toxic plants and iron over-load in foals generally have a poorer prognosis. Hepatic lipidosis has a good prognosis if the primary disorder is quickly corrected and there is a rapid and dramatic response to medical therapy. Triglyceride level is not a great predictor of prognosis.