Equine Liver Disease

Question 1

Purpose of the liver.

Answer 1

Protein metabolism:
- synthesis.
- incl. factors involving coagulation.
- gluconeogenesis from amino acids.
- eliminating ammonia — major toxic by-product of amino acid catabolism.
Carbohydrate metabolism:
- synthesis, storage, release of glucose.
Lipid metabolism:
- esterify FFA’s into triglycerides for export to other tissues.
- oxidise FFA’s to acetyl coenzyme A (for TCA cycle).
Excretion of bile:
- no gall bladder.
- continuous flow.
Detoxification:
- biotransformation of endogenous and exogenous compounds.
Mononuclear phagocyte system:
- hepatic macrophages / Kupffer’s cells.
Miscellaneous:
E.g. vitamin storage.

Question 2

Hepatic insufficiency.

Answer 2

Inability of liver to perform its normal functions properly.
Pathology may affect one or several functions but not necessarily all.
Most hepatic functions not impaired until greater than 80% of hepatic mass lost.
Liver can regenerate.
Hepatic disease may be subclinical.

Question 3

Clinical signs of hepatic insufficiency.

Answer 3

Variable, non-specific, depend on extent and duration of hepatic disease.
Regardless of cause, usually 80% liver mass lost before see clinical signs.
Despite duration of hepatic disease, onset of clinical signs often abrupt.
Common:
- depression, anorexia, colic, hepatic encephalopathy, weight loss, icterus.
Less common:
- photosensitisation, diarrhoea, bilateral laryngeal paralysis, bleeding, ascites, dependent oedema.
There are other rare signs.

Question 4

Hepatic encephalopathy in horses.

Answer 4

Complex syndrome.
Abnormal metal status.
Variable clinical signs.
- all are manifestations of augmented neuronal inhibition.
Potentially reversible.

Question 5

Hepatic encephalopathy clinical signs.

Answer 5

Stage 1 probably missed in most equine patients.
- subtle impairment of intellect.
Stage 2
- motor function, intellectual ability and consciousness impaired:
— depression, head pressing, circling, ataxia, aimless walking, yawning.
Stage 3
- aggressive, periods of stupor, recumbent, coma.

Severity of encephalopathy corresponds to degree of hepatic dysfunction.
Neither parameter corresponds with type or reversibility of the underlying hepatic disease.

Question 6

Cause and pathophysiology of hepatic encephalopathy?

Answer 6

Cause of hepatic encephalopathy is insufficient hepatocellular function, irrespective of the cause of the liver disease.
Pathogenesis is unclear and multifactorial. Includes:
- accumulation of toxins in the blood (incl. ammonia).
- augmented activity of inhibitory neurotransmitters.

Question 7

Diagnosis of hepatic encephalopathy.

Answer 7

Presence of neurological signs of cerebral dysfunction.
With physical exam and lab findings compatible with liver disease.

Question 8

Icterus (jaundice).

Answer 8

Caused by hyperbilirubinaemia with subsequent deposition of pigment in tissues causing yellow discolouration.
Most apparent in mucosa and sclera.
Some horses are a bit yellow anyway

Question 9

Disease states resulting in hyperbilirubinaemia.

Answer 9

Increased production of bilirubin (haemolysis, intracorporeal haemorrhage).
Impaired uptake and conjugation of bilirubin (liver disease, anorexia, prematurity).

Question 10

Impaired excretion of bilirubin into biliary tract.

Answer 10

Regurgitation icterus.
- blockage of bile with cholangitis, hepatitis, cholelithisasis, neoplasia, fibrosis etc.
- if conjugated bilirubin more than 30% greater than normal, indicative cholestasis.

Question 11

Weight loss as a clinical sign of liver disease in the horse.

Answer 11

Most consistent clinical sign but still not seen in all cases.
Due to anorexia and loss of normal hepatocellular metabolic activities.

Question 12

Hepatogenic photosensitisation.

Answer 12

Abnormally heightened reactivity of the skin to UV.
- increased blood concentration of a photodynamic agent — phylloerythrin if hepatogenic.
- UV + phylloerythrin = free radicals = cell membrane damage and necrosis.
- unpigmented skin.

Question 13

Diagnosis of hepatic disease - lab.

Answer 13

Non-specific clinical signs and variable lab findings cofound definitive diagnosis of hepatic disease.
Lots of tests:
- need to understand sensitivity and specificity.
- so you can choose appropriate tests.
- then be able to interpret them.
Lab findings can also be useful for therapy and prognosis.

Question 14

Evaluation of bilirubin.

Answer 14

Serum bilirubin concentration is NOT a sensitive indicator of liver disease in horses.
Total bilirubin increased in conc 25% liver disease cases.
Disease, not necessarily failure.
Need to know fractions.
- Conjugated (direct) + unconjugated (indirect) = total bilirubin.

Question 15

Evaluation of bilirubin.

Answer 15

Increase in unconjugated bilirubin seen in hepatic disease (usually acute hepatocellular).
- but also anorexia, haemolysis, others.
Conjugated bilirubin:
- increase of over 25% more specific to hepatic disease.
- increase of over 30% more specific to cholestasis.

Question 16

Serum bile acid concentration.

Answer 16

Enterohepatic circulation normally removes >90% bile acids.
Blood concentration increases with liver disease.
Quantitation = excellent screen of liver failure.
Don’t need to do pre and post prandial! - no gall bladder — designed to eat all the time.
Fasting for longer than 3 days will confound results.

Question 17

Tests of protein synthesis.

Answer 17

Hypoalbuminaemia:
- non-specific.
- >80% liver affected for >3wks.
Evaluation of haemostasis:
- non-specific.
Liver removes ammonia from circulation, converts to urea:
- increased ammonia / decrease in BUN.
- not specific.

Question 18

Liver enzymes - general points.

Answer 18

Hepatocellular necrosis results in release of enzymes.
Increased serum activity may be indicative of active hepatic disease.
Wide variation in normal and abnormal, liver specificity, inducibility.
Bit of a minefield.

Question 19

Liver enzymes - general points.

Answer 19

Hepatocellular necrosis results in release of enzymes.
Increased serum activity may be indicative of active hepatic disease.
Wide variation in normal and abnormal, liver specificity, inducibility.
Bit of a minefield.

Question 20

Best liver enzymes to use and points about them.

Answer 20

SDH = sorbitol dehydrogenase.
ARG = arginase.
GLDH = glutamate dehydrogenase.

Liver-specific and not inducible.
Specific for hepatocellular disease.
But not type of disease.
All usually better for acute disease.
SDH would be best but does not survive in a tube.

Question 21

Other liver enzymes and points about them.

Answer 21

AST = aspartate aminotransferase.
ALP = alkaline phosphatase.
LDH = lactate dehydrogenase.
ALT = alanine aminotransferase.

Also found in other tissues.
Or are inducible.
So low specificity.

Question 22

Liver enzymes - GGT.
And points.

Answer 22

Gamma-glutamyltransferase.
Specific for hepatic disease in horses.
Most sensitive indicator of hepatic disease.
Hepatocellular damage.
Continues to rise for 1-2 weeks after liver improving.
May not increase in chronic disease.
Higher in young foals (IgG).

Question 23

First line lab tests.

Answer 23

GGT for damage.
- but normal values may not mean absence of liver disease.
Bile acids for liver function.

Think before you send of blood tests:
- can you interpret the result?
- will it change what you do?
- don’t waste time and money.
- fine to send off for live panel but do engage your brain.

Question 24

Ultrasonography of the liver to diagnose liver disease.

Answer 24

Can see quite a lot of the liver but not all of it.
Look both sides.
Assess shape, size, changes on parenchyma, dilated bile ducts, obstructions with choleliths.

Question 25

Biopsy of the liver to diagnose liver disease.

Answer 25

Ultrasound guided or follow landmarks.
Simple.
Check they can clot first.
But usually low risk.
Not if hepatic lipidosis:
- can make the liver shatter.
Very useful for diagnosis and therefore treatment.
Scoring system for biopsy very useful for prognosis.

Question 26

Treatment for hepatic insufficiency main aims.

Answer 26

Largely supportive.
Maintain until enough liver regenerates to provide adequate function.
If severe hepatic fibrosis, adequate regeneration often not possible.

Question 27

Treatment of hepatic insufficiency.

Answer 27

Care with sedation (low dose xylazine).
- liver metabolises sedation.
Correct fluid deficit, acid-base, electrolyte imbalances.
- IV fluids spike appropriately.
If off food, spike fluid to be 5% glucose.
Diet:
- when appetite returns, diet is best way to manage HE or chronic liver disease.
- high carbohydrate, low in good quality protein.
Multiple small feed as impaired gluconeogenesis.
Oat hay - low in protein.
Grass (but beware sunlight - if photosensitisation).
Vitamins B, K, folic acid weekly.
Reduce absorption of enteric parasites by enteric bacteria by giving paraffin / magnesium sulphate by NG tube.
Reduce production of toxic metabolites by enteric bacteria:
- neomycin, metronidazole.
- lactulose.
— evidence questionable —> risk diarrhoea.

Question 28

Prognosis of hepatic insufficiency?

Answer 28

Depends on severity and type of underlying disease.
Focal or mild-moderate acute hepatic disease have best chance for hepatic regeneration.
- guarded to fair prognosis with supportive care.
Severe hepatic fibrosis and chronic liver disease have poorer prognosis regardless of cause — inability to compensate for lost hepatic function.
Severe signs of insufficiency = poorer prognosis.

Question 29

What may a chronic disease show?

Answer 29

Hyperglobulinaemia.
Hypoalbuminaemia.
Fibrosis.

Question 30

Theiler’s disease.

Answer 30

Acute.
One of the most common causes of acute hepatic failure but still quite rare.
Usually received an equine origin antiserum 4-10 weeks before.
‘Serum associated hepatitis’.
Treat with supportive care.

Question 31

Bacterial hepatitis.

Answer 31

Acute.
Primary is rare.
Secondary more common e.g. after cholelithiasis, intestinal obstruction, anterior enteritis.
Liver biopsy for histology and culture.
Supportive therapy.
Appropriate ABX for 4-6w.

Question 32

Hepatic lipidosis.

Answer 32

Acute.
Secondary to hyperlipaemia.
Supportive care.
Treat hyperlipaemia.

Question 33

Megalocytic hepatopathy.

Answer 33

Chronic.
Most common cause of chronic liver failure.
Ingestion of pyrrolizidine alkaloid containing plants.
- ragwort but many others.
— Poor palatability but will eat in bay or if nothing else to eat.
Cumulative toxicity.
Toxin stops cell division - hepatocytes enlarge — ‘megalocytes’.
—> fibrosis when megalocytes die.
—> extensive fibrosis results in the liver shrinking.
Clinical signs occur 4w-12m after ingestion.
Abrupt onset HE and photosensitisation late in disease.
Earlier anorexia, weight loss, icterus.
Diagnosis = history, clinical signs, lab tests, biopsy.
Supportive care but generally poor prognosis as fibrosis limits regeneration.

Question 34

Cholelithiasis.

Answer 34

Chronic.
Not v common.
Icterus, colic, pyrexia, weight loss.
- Often intermittent signs.
Conjugated bilirubin more than 30% increased often.
Many have dilated bile ducts on U/S.
Biopsy for Dx.
May have underlying bacterial cause.
Long term ABX (culture biopsy).
Surgery to remove choleliths but patient don’t do well with this.

Question 35

Non-septic hepatitis.

Answer 35

Chronic.
Non-septic (lymphoplasmacytic) hepatitis.
Inflammatory infiltrate without infection.
Unknown cause.
Some likely viral, toxin in hay.
Treat with corticosteroids, azathioprine.
Monitor with biopsies — change more accurate then enzyme testing.