Laboratory diagnosis: Treatment and management of liver disease in the horse (Proceedings)
Biochemical testing is imperative in the diagnosis of both liver disease and liver failure. Biochemical results can be helpful in narrowing the differentials for the liver failure and, when evaluated over time, can help predict prognosis. Biochemical testing can also be used to identify hepatotoxin exposure (e.g., pyrollizidine alkaloid) (Curran 1996), or drug-induced liver disease (seen most commonly in foals). Liver specific enzymes include sorbital dehydrogenase (SDH) or glutamate dehydrogenase (GDH) 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 would be expected to increase in the serum with mild hepatocyte injury. It has a short half life (T½) which can be helpful in determining resolution or progression of the hepatic insult (Bernard 1989), although rarely in severe cases of hepatic failure it may return to normal range in spite of a fatal outcome. GGT often continues to elevate for a few days (presumably due to biliary hyperplasia) after a hepatic insult is no longer present. Although GGT elevations are greatest with biliary disease, there is some release into the plasma with hepatocellular injury (Noonan 1981) and it is the single best screening test for hepatic disease in the horse. It is rare that a horse with liver disease will not have elevated plasma/serum GGT. The magnitude of elevation in hepatic-derived enzymes may not always correspond with functional abnormalities and should, therefore, be considered test of disease and not function. Magnitude of increases in hepatic enzymes (especially GGT) should not be used to determine prognosis. For example, I have successfully treated one horse with cholangiohepatitis that had a GGT value of 2500 IU/L. Prognosis is best determined by function test abnormalities, etiology of the hepatic failure, and presence of hepatic encephalopathy. HCT and serum iron are frequently high in horses with severe liver disease. Marked elevation in serum iron in the adult horse is most commonly seen with either hepatic and/or hemolytic disease. Race horses occasionally 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 and indirect bilirubin, blood ammonia, prothrombin and partial thromboplastin time, bile acids and gamma globulins (with chronic disease). An increase in direct bilirubin is a highly sensitive marker of liver failure. 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 horses with intestinal ileus sometimes have elevations in direct bilirubin with minimal evidence of hepatocellular dysfunction. Treatment should focus on the sepsis and intestinal ileus in those cases. Increases in indirect bilirubin is also a sensitive test of liver failure, but lacks specificity since elevations may also occur with anorexia, hemolysis, or on a rare occasion marked elevation in an otherwise healthy horse (presumed congenital deficiency in glucuronyl transferase) (Divers 1993). There may be a decrease in BUN, fibrinogen, and albumin (with chronic disease and failure). Serum or plasma bile acids can be an early predictor of liver failure when values rise above 30 μmol/L. Mild elevations in bile acids (as high as 20 μmol/L) may be seen with anorexia. Serum triglycerides are increased in equines with hepatic lipidosis and the magnitude of the triglyceride increase may correlate with prognosis (Mogg 1995). In foals with hepatic failure, hypoglycemia is often present, while in adult horses, blood glucose is more commonly normal or increased but may be low (McGorum 1999). Plasma lactate is frequently high and bicarbonate low in horses with fulminant hepatic failure.
There is little published evidence-based medicine regarding the treatment of liver disease in the horse. Even in human medicine, most treatments of liver disease are supportive and often unsubstantiated by clinical trials. For example, pentoxifylline and acetylcysteine are frequently mentioned as treatments of liver disease, but efficacy data is limited (Sklar 2004).