Andy Durham Liver Disease Slides PDF

FORUM 1. Recognise the common presentations and clinical signs associated with liver disease in the horse 2. Outline the diagnostic approach to equine liver disease. 3. Identify key prognostic indicators relative to equine liver disease 4. Summarise the therapeutic options available...

FORUM 1. Recognise the common presentations and clinical signs associated with liver disease in the horse 2. Outline the diagnostic approach to equine liver disease. 3. Identify key prognostic indicators relative to equine liver disease 4. Summarise the therapeutic options available for treating horses with liver disease  Important distinction between hepatic disease and hepatic insufficiency  Subclinical liver disease is common  Many horses suffer from persistent increases in liver enzymes  Outbreaks of (subclinical) liver disease are common  Liver biopsy is usually required to fully investigate a case of liver disease -of hepatic insufficiency  lethargy/inappetance  weight loss  colic  photosensitisation  encephalopathy  diarrhoea  jaundice  oedema  coagulopathy  Depression  Circling  Aimless wandering  Headpressing  Blindness  yawning  Coma  Bilateral laryngeal paralysis 1. Neurotoxic products of gut origin Ammonia  glutamine  osmotic astrocyte/neuron swelling Mercaptans Phenols 2. Disturbances in neutrotransmitters e.g. ↑ inhibitory GABA; ↓ excitatory dopamine 3. Increased cerebral concentrations of an endogenous benzodiazepine-like substance 4. Other factors hypoxia electrolyte abnormalities acid-base disturbance hypoglycaemia -of hepatic insufficiency This means:  >70% functional mass affected?  irreversible pathology more likely  prognosis poorer  biopsy more risky  everybody loses! Subclinical/mild signs This means:  2-3  disappointing performance months) indicates: ◦ GGT 180 IU/L, bile acids 6 µmol/L persistent pathology?  try nutraceuticals/supplements? ◦ GGT 210 IU/L, bile acids 4 µmol/L failure of treatment?  try antimicrobials? failure to identify and eliminate ◦ GGT 165 IU/L, bile acids 5 µmol/L the cause?  try glucocorticoids? ◦ GGT 190 IU/L, bile acids 7 µmol/L  …………………………  ………………………… 2. Epidemiologic clues What might the cause be? hepatotoxicity septic cholangitis cholelithiasis Ben viral GGT 180 GLDH 56 parasitic SBA 6 neoplasia immune-mediated (chronic/active) 2. Epidemiologic clues What might the cause be? hepatotoxicity septic cholangitis cholelithiasis Ben Zorba Digby Buddy Fred Robin viral GGT 180 78 98 216 26 66 GLDH 56 24 18 43 7 26 parasitic SBA 6 4 5 2 5 7 neoplasia immune-mediated (chronic/active) 2. Epidemiologic clues What might the cause be? hepatotoxicity septic cholangitis cholelithiasis Ben Zorba Digby Buddy Fred Robin viral GGT 180 78 98 216 26 66 GLDH 56 24 18 43 7 26 parasitic SBA 6 4 5 2 5 7 neoplasia immune-mediated (chronic/active) Always blood test herdmates  Possible causes: Toxicity Pyrrolizidine alkaloids Iron Mycotoxins (aflatoxins) fumonisin B1 Infectious disease Fasciola hepatica Viral hepatitis Equine Hepacivirus Equine Parvovirus (Theiler’s Disease Associated Virus) (Equine Pegivirus) Liver fluke (Fasciola hepatica) rare but recognised (especially areas with cattle/sheep infections) antemortem diagnosis very challenging detection of Fasciola eggs in faeces frequently non-patent insensitive even when eggs are shed coproantigen assays extremely poor diagnostic value serologic assays variable reliability problems also exist with resistance to triclabendazole Viral Hepatitis precise relevance to equine liver health not yet established at least 2 viruses appear to be: common international hepatotrophic associated with increased liver enzymes Equine Hepacivirus Equine Parvovirus  Occasionally specific abnormalities are found with hepatic ultrasound but……….most horses with significant liver disease have unremarkable hepatic images useful for:  providing occasional diagnostic information  identifying appropriate site(s) for biopsy  reducing the risk of biopsy 1. Sedate 2. Identify site with ultrasound 3. Determine depth/angle of the biopsy 4. Clip and scrub 5. Local anaesthetic 6. Stab incision 7. Insert biopsy instrument 8. Operate biopsy instrument 9. Place biopsy into formalin/plain tubes 10. Prophylactic antimicrobial/NSAID  1. confirm liver disease is definitely present ? 2. (attempt to determine aetiology) rules-in or rules-out a few conditions  3. guides choice of specific therapy anti-fibrotic, anti-microbial, phlebotomy for haemosiderosis, etc…  4. indicates prognosis  Some findings specific for aetiology : Pyrrolizidine alkaloids Haemosiderosis Septic cholangitis Neoplasia..but mostly biopsies don’t indicate aetiology e.g. - moderate non-septic periportal inflammation, - mild biliary hyperplasia - early portal fibrosis - multifocal individual necrotic hepatocytes with neutrophilic infiltrates  mild moderate severe Fibrosis Irreversible cytopathology (megalocytosis/necrosis) Inflammatory infiltrate Haemosiderin accumulation Biliary hyperplasia Durham et al (2003) EVJ 35, 534.  mild moderate severe Fibrosis - 2 4 Irreversible cytopathology 1 2 2 (megalocytosis/necrosis) Inflammatory infiltrate - 1 2 Haemosiderin accumulation - - 2 Biliary hyperplasia - 2 4 Durham et al (2003) EVJ 35, 534.  mild moderate severe Fibrosis 2 Irreversible cytopathology 1 2 (megalocytosis/necrosis) Inflammatory 2 infiltrate Haemosiderin accumulation Biliary 2 hyperplasia  30 25 survivors non-survivors Number of cases 20 15 12x 46x 10 P