Clinical Pathology of Liver Disease in Horses.

This article explains how veterinarians use blood tests to detect liver injury, impaired bile flow, and loss of liver function in horses. It highlights that enzyme signs of damage and cholestasis are common, whereas overt functional failure is less frequent because the equine liver has a large reserve capacity.

Scope and clinical relevance

• Defines how routine serum chemistry, targeted enzyme assays, and select liver function tests are used to evaluate equine liver disease.
• Distinguishes between processes: hepatocellular damage (injury to liver cells), cholestasis (impaired bile flow), and reduced hepatic function (synthetic and clearance failure).
• Explains why many horses show biochemical evidence of injury and cholestasis without frank liver failure, guiding diagnosis, monitoring, and prognosis.

Enzymes that indicate hepatocellular injury

• AST (aspartate aminotransferase)
  • Source: liver and skeletal muscle; not liver-specific.
  • Interpretation: increases with hepatocellular damage but must be interpreted alongside CK (creatine kinase) to exclude primary myopathy.
  • Kinetics: longer half-life (days), so elevations can persist after acute injury.
• SDH (sorbitol dehydrogenase)
  • Source: hepatocyte cytosol; liver-specific in large animals.
  • Interpretation: sensitive marker of acute hepatocellular injury; often rises early and markedly.
  • Practical note: enzyme is labile; prompt processing is required for reliable results.
• GLDH (glutamate dehydrogenase)
  • Source: hepatocyte mitochondria; liver-specific.
  • Interpretation: increases with hepatocellular necrosis; complements SDH and is more analytically stable.
• ALT (alanine aminotransferase)
  • Limited utility in horses due to low hepatic activity; not a primary marker in this species.
• LDH (lactate dehydrogenase)
  • Nonspecific; can increase with liver or muscle injury; used adjunctively if at all.

Enzymes that indicate cholestasis (bile flow impairment)

• GGT (gamma-glutamyl transferase)
  • Source: biliary epithelium and canalicular membranes.
  • Interpretation: most sensitive and specific indicator of cholestasis and biliary disease in horses; often markedly elevated in cholangiohepatitis and cholelithiasis.
  • Kinetics: relatively long half-life; persistent elevation suggests ongoing or chronic biliary pathology.
• ALP (alkaline phosphatase)
  • Source: liver (bile duct epithelium) and bone.
  • Interpretation: can increase with cholestasis, but is less specific than GGT; consider age and bone turnover (especially in growing animals).

Markers of hepatic synthetic capacity (function)

• Albumin
  • Decreases with chronic or severe hepatic insufficiency (long half-life delays onset of hypoalbuminemia).
  • Differentials for low albumin include protein-losing enteropathy/nephropathy and malnutrition.
• Urea/BUN
  • Decreases when urea cycle function is impaired (reduced conversion of ammonia to urea).
  • Interpret with diet (low-protein intake) and renal function; baseline BUN is naturally low in horses.
• Coagulation profile (PT, aPTT ± fibrinogen)
  • Prolongation reflects reduced synthesis of clotting factors in advanced liver disease.
  • Cholestasis can also cause vitamin K malabsorption, compounding coagulopathy.
  • Critical for risk assessment before liver biopsy or invasive procedures.
• Cholesterol
  • May decrease with chronic hepatic failure; changes are less consistent than in small animals and must be interpreted in context.

Bilirubin: integrating hepatocellular injury and cholestasis

• Unconjugated (indirect) bilirubin
  • Increases with fasting/anorexia in horses due to reduced hepatic uptake; a common benign cause of icterus in this species.
  • Also increases with hemolysis; correlate with anemia and hemolysis indicators.
• Conjugated (direct) bilirubin
  • Increases with intrahepatic or extrahepatic cholestasis (impaired excretion).
  • A higher direct fraction supports cholestatic disease, especially when GGT is elevated.
• Mixed patterns
  • Many equine hepatic disorders produce combined increases (e.g., hepatocellular injury plus cholestasis), so fractionation helps localize predominant processes.

Clearance and excretory function tests

• Serum bile acids (SBA)
  • Assess hepatic uptake and excretory function; increase with hepatocellular dysfunction, cholestasis, or portosystemic shunting.
  • Horses lack a gallbladder, so fasting/postprandial variation is minimal; a single resting SBA is generally informative.
  • Useful for detecting functional impairment even when enzymes mainly reflect injury.
• Ammonia
  • Elevates with impaired hepatic clearance and urea cycle failure; correlates with risk of hepatic encephalopathy.
  • Preanalytical care is critical (prompt separation, chilling, avoidance of hemolysis) to prevent artifactual increases.
  • Ammonia tolerance tests are rarely needed and can be risky in encephalopathic animals.

Why decreased function is less common: hepatic reserve

• The equine liver has substantial functional reserve; synthetic and clearance capacities often remain adequate until a large proportion of hepatocytes are compromised.
• Consequently, many cases show elevated injury/cholestasis enzymes without concurrent hypoalbuminemia, coagulopathy, or high bile acids early in disease.
• Functional failure typically signals extensive or chronic disease and carries a more guarded prognosis.

Practical stepwise interpretation

• Localize injury vs cholestasis
  • Predominant SDH/GLDH ± AST increases suggest hepatocellular injury.
  • Predominant GGT ± ALP increases suggest cholestasis/biliary disease.
  • Check CK to avoid misattributing muscle injury to the liver when AST is elevated.
• Assess function next
  • Evaluate albumin, BUN, bilirubin fractions, SBA, and coagulation times.
  • Use ammonia levels when neurologic signs raise concern for hepatic encephalopathy.
• Contextualize with clinical findings
  • Consider anorexia-induced hyperbilirubinemia, hemolysis, age-related ALP/GGT changes, and bone turnover.
  • Integrate history (e.g., exposure to hepatotoxins such as pyrrolizidine alkaloids, recent biologics/sera), ultrasound, and, when safe, liver biopsy for etiology and staging.
• Monitor trends
  • Falling SDH/GLDH indicate resolution of acute hepatocellular injury; persistent or rising GGT suggests ongoing cholestasis.
  • Worsening SBA, ammonia, or coagulation times signal declining functional capacity and higher risk.

Typical patterns in common equine hepatobiliary disorders

• Cholangiohepatitis or cholelithiasis
  • Marked GGT elevation; ALP variably increased.
  • Bilirubin often increased with a higher conjugated fraction; SBA elevated.
  • AST/SDH/GLDH may be mildly to moderately increased depending on concurrent hepatocellular injury.
• Acute toxic or inflammatory hepatopathy (e.g., Theiler’s disease, some plant toxins)
  • Rapid, high increases in SDH/GLDH; AST follows and persists longer.
  • Mixed hyperbilirubinemia; SBA often elevated.
  • Potential coagulopathy and hyperammonemia in severe cases.
• Chronic hepatopathy/fibrosis (e.g., pyrrolizidine alkaloid toxicity)
  • Variable or even modest enzyme activity once end-stage; GGT may remain elevated if biliary fibrosis is present.
  • Functional deficits become evident: low albumin, high SBA, prolonged PT/aPTT, possibly low cholesterol and BUN.

Pitfalls and confounders

• Fasting/anorexia
  • Common cause of unconjugated hyperbilirubinemia without primary liver disease in horses.
• Muscle injury
  • Elevates AST and LDH; concurrent CK testing helps differentiate from hepatic causes.
• Age and physiologic states
  • Growing animals can have higher ALP; perinatal factors and colostrum can influence GGT in foals.
• Preanalytical issues
  • Hemolysis and delayed sample processing can artifactually affect ammonia, SDH, and other analytes.

Clinical takeaways

• Start with enzyme patterns to identify hepatocellular injury and cholestasis, then layer on function tests to determine severity and prognosis.
• Expect many equine liver diseases to show injury and cholestasis with preserved function early, due to substantial hepatic reserve.
• Use bile acids, ammonia, and coagulation testing selectively to detect functional compromise, guide procedures (e.g., biopsy), and monitor progression or recovery.