Practical Internal
Medicine
Liver Disease
Wendy Blount, DVM
Nacogdoches, TX
Liver Disease
Asymptomatic Elevated Liver Enzymes
Chronic Liver Disease
Acute Liver Failure
Elevated Liver Enzymes in the Well Pet
Cats are not little dogs
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Cats with persistently elevate enzymes should be
worked up
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T1/2 of liver enzymes hours, not days as in the dog
cats have 1/3 the liver SAP compared to dogs
Cats with significant cholangiohepatitis can have
normal liver enzymes
GGT elevated significantly exceeds SAP elevation
only in hepatic lipidosis
High bile acids in the cat indicates liver disease
nearly 100% of the time
Any bilirubinuria in the cat is significant
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Can be used to monitor cholestatic disease
Elevated Liver Enzymes in the Well Pet
Dogs… Grrrr…
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Explore the history for untreated problems
Treat empirically for reactive hepatopathy first
Treat problems that can insult the liver
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Occult infections – urinary, metritis, prostatitis, etc.
Treat for sublinical cholangiohepatitis
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Amoxicillin 10 mg/lb PO BID x 3 weeks
Put on a supplement to curtail damage by hepatic
inflammation
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Denosyl, Denamarin – dosage chart in package
Milk thistle
Elevated Liver Enzymes in the Well Pet
Milk Thistle
• Dried herb: 15-20mg/lb SID (1.5-3% silymarin)
• Concentrated extract: 2-5 mg/lb BID (7080% silymarin)
• Alcohol concentrated extract: 2-5 mg/lb BIDTID (70-80% silymarin)
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NOTE: some extracts are whole herb extracts,
and these are hard to dose high enough to be
effective
Elevated Liver Enzymes in the Well Pet
3. Recheck Liver enzymes in 30 days
4. Proceed with further diagnostics for liver
disease
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Assess liver function with bile acids
Abdominal ultrasound and liver cytology
ACTH stimulation if signs of Cushing’s Disease
5. If Step 4 reveals significant undiagnosed
problems, consider liver biopsy or referral
for splenic portagram to rule out PSS
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Ultrasound guided liver biopsy (50% diagnostic)
Surgical liver biopsy
Scotties can have very high liver enzymes
with no pathology
Undiagnosed Problems Causing
Reactive Hepatopathy
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Occult infection
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Urinary tract
Metritis, prostatitis
Dental Disease
Disease of organ drained by portal vein
Severe muscle disease
Hypoxia – heart failure, respiratory disease,
severe anemia
Other Problems Causing Elevated
SAP with normal ALT
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Bone growth or osteolysis
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Puppies and kittens
Bone neoplasia
Osteomalacia
Hyperparathyroidism
GI Disease
Pregancy
Kidney Disease
Drug Therapy
Pattern Recognition - Liver Disease
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High liver enzymes
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ALT – hepatocellular disease
SAP, GGT – cholestasis
Can be normal with prolonged chronic disease
Low albumin
Low fasting glucose
High prost-prandial glucose
Low BUN
Abnormal cholesterol, triglycerides
Ammonium biurate crystalluria
Prolonged recovery from anesthesia
Pattern Recognition - Liver Disease
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Ascites – transudate or modified transudate
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Increased sodium retention, portal hypertension,
hypoalbuminemia
PU-PD
Acholic feces
Dark urine (orange) precedes icterus
Icterus
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Suspect if high bili with normal PCV
Seen best on sclerae, penile mucosa, soft palate, under
the tongue
Icterus occurs when 10% of liver function remains
Look for cholestatic disease if signficant bilirubinemia
without bilirubinuria (delta bili)
Pattern Recognition - Liver Disease
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Tendency to sepsis
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Hepatic RE system detoxifies blood from the gut
(portal circulation)
GI hemorrhage death spiral
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Decreased hepatic clearance of gastrin
Factor’s, AT3 not produced adequately
Increased bile acids stimulated HCl secretion
DIC
Bleeding exacerbates hepatic encephalopathy
Large bleed can cause depletion coagulopathy
Hemorrhage elsewhere only when near death
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Petecheia, bruising, bleeding into cavities
Pattern Recognition - Liver Disease
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PSS in Cats
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Salivation – most common clinical sign
Hepatic encephalopathy
Vomiting and diarrhea
Bile Acids
1. 12 hour fast – red top tube
2. Feed 1-2 Tablespoons a/d
3. 2 hour post prandial red top tube
If not fasted, doing only the post-prandial can be a
good screen for liver insufficiency
Can’t run bile acids on a lipemic sample
Overfeeding can induce HE
Bile Acids
High bile acids in the blood can cause gastric
hyperacidity in the stomach and diarrhea
Bile acids >30-40 umol/L in the dog and >20-30
umol/L in the cat warrant further investigation
Idexx SNAP test tells you
• <12 umol/L
• 12-25 umol/L
• >25 umol/L
Ammonia
Normal in the dog 20-80 ug/dl
Normal in the cat 20-120 ug/dl
Elevated resting ammonia is significant
Idexx VetTest/Catalyst does ammonia assays
Falsely increased by hemolysis
Centrifuge and decant within 30 minutes
Run assay within 2 hours
Sending to outside lab can be difficult
Ammonia
Ammonia Tolerance Test:
1. 12 hour fast – red top tube
2. NH3Cl capsules 45 mg/lb max dose 3g PO
3. 30 minutes later – red top tube
Increase should be <32%
100% sensitive for PSS
DO NOT GIVE NH3Cl if resting ammonia elevated
• Can induce HE
Chronic Liver Disease
DDx Chronic Liver Disease
Immune Mediated Cholangiohepatitis
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Westie, Doberman, Skye terrier, cats
Copper Storage Disease
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Dobermans, Bedlingtons
Portosystemic Shunt
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Congential or Acquired
Extrahepatic – Yorkie, schnauzer, poodle, dachshund
Intrahepatic – Doberman, Golden, Lab, Irish Setter,
Samoyed, Irish Wolfhound
Microvascular Dysplasia
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Yorkie, Cairn Terrier
DDx Chronic Liver Disease
Bacterial Cholangiohepatitis
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cats
Fungal Hepatitis
Heterobilharzia americanum
Chronic Liver Disease usually Diagnosed
by Liver Biopsy
Tx Chronic Liver Disease
Proper Diet
Treat chronic infection
Treat chronic inflammation
Treat cholestasis
Treat fibrosis
Treat copper accumulation
Treat GI side effects
Manage hepatic encephalopathy
Manage ascites
DDx Acute Liver Failure
Hepatotoxins
Septicemia
Pancreatitis
Infectious Canine Hepatitis (CAV)
Hypoxia/Ischemia
Exacerbation of Chronic Liver Dz
SIRS
DDx Icterus
Pre-Hepatic – Hemolysis
Hepatic
Post-Hepatic
Pancreatitis
Pancreatic Neoplasia, Abscess, or Granuloma
Liver, Bile Duct, Duodenal Neoplasia, Abscess or Granuloma
Biliary Mucoceole
Cholecystitis
Cholelithiasis
Duodeonal foreign body
PSS and steroid hepatopathy dogs are almost never icteric
DDx Acute Liver Failure
Hepatotoxins
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Acetominophen
Aflatoxins
Anabolic Steroids
Anticonvulsants
Antineoplastics
Arsenicals
Carprofen
Diazapem
Diethylcarbamazine
Griseofulvin
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Itraconazole
Kava Kava
Ketoconazole
Oxabendazole
Mebendazole
Mitotane
Mushrooms
Sago Palm (seeds)
Sulfonamides
Thiabendazole
TMPS
Hepatic Encephalopathy
Abnormal mental status in patients with severe
hepatic insufficiency
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Severity of HE does not always correlate with severity
of liver disease
Things that can precipitate an HE episode:
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Increased protein intake, GI hemorrhage
Dehydration, diuretic therapy
Barbiturates and other sedatives
Uremia
Infection, endoctoxemia, constipation, increased aneaerobes
in the colon
Increased methionine intake
Progression of
Hepatic Encephalopathy
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Mildest form – anorexia and lethargy
May progress to weight loss
Ataxia
Confusion, stupor, loss of training
Pacing and wandering
Twitching progressing to seizures
Vomiting, diarrhea
Temporary blindness
Dementia, seizures, coma
Multifocal deficits on neurologic exam
Tx Acute Liver Failure
Correct fluid an electrolyte imbalances
Treat Coagulopathy
Treat hypoglycemia
Treat hepatic encephalopathy
Control GI hemorrhage
Treat Sepsis if present
Sebastian
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9 year old neutered male pit bull
2 year history of lower cervical disc disease
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Several episodes of pain and CP deficits
Responded to treatment with prednisone and cage
rest
1 week ago ataxia and falling, and vocalizing
every time he moves
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The morning after a fight with another dog
Tx prednisone, methocarbamol, Tramadol, cage
rest – no response for 4 days
Sedated for radiographs
Sebastian
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4 days ago Sedated for radiographs
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mid-abdomen 8cm soft tissue mass
no significant enlargement of liver, spleen, R kidney
Cervical & lumbar intervertebral disc calcification
vomited large amount of fluid with coffee grounds
after sedation
Tx carafate, IV fluids, metronidazole, amoxicillin
Albumin 2.1 g/dl (2.2 g/dl low normal)
SAP 2119 U/L
ALT 1434 U/L
Bili 8.2 mg/dl
HCT 30.8%
Sebastian
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Referred for ultrasound today
Exam
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Can not walk
Muscle tremors and very jumpy when touched
Icteric skin
Abdomen tense and difficult to palpate
Very large urinary bladder
Scleral injection – owner says had been present for
30 days
Sebastian
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Neuro Exam
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Unable to walk, unable to assess postural
reflexes and CP
Cranial nerves normal
Spastic paresis in all 4 limbs (UMN reflexes)
Conscious motor activity in all 4 limbs
Lower cervical pain
Dx - Lower cervical spinal cord disease
Catheterized bladder and removed 1.5L of
orange urine (bilirubin crystals)
Hx – has been on clomipramine for some time,
for anxiety
Sebastian
Problem List
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Cervical myelopathy and tetraparesis
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Surgery not an option for these owners
Icterus – likely hepatic, post-hepatic and hemolysis
can not be ruled out
Hematemesis – prednisone, liver failure, spinal cord
injury
Twitching – hepatic encephalopathy, metronidazole
toxicity, serotonin syndrome
Mid abdominal mass
Mild anemia
Sebastian
Sebastian
Sebastian
Sebastian
Radiographs
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Large amount of air in the stomach
Gastric axis shifted cranially
Normal Dog
Radiographs
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Large amount of air in the stomach
Gastric axis shifted cranially
Sebastian
Radiographs
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Large amount of air in the stomach
Gastric axis shifted cranially
Sebastian
Radiographs
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Large amount of air in the stomach
Gastric axis shifted cranially
Intestines appear distended with fluid
No mid abdominal mass seen
Increased soft tissue density in right cranial abdomen
Cervical and lumbar spondylosis
Cervical and lumbar mineralized disc material
Disc material in the spinal foramina
Dx – microhepatia
Dx – degenerative disc disease
Sebastian
Abdominal Ultrasound
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Difficult because of the great amount of air in
the stomach, due to aerophagia
Small areas of the liver seen, hyperechoic,
mottled in echotexture
Gall bladder not seen
Many fluid filled loops of bowel
PT, PTT - normal
Sebastian
Plan
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Discontinue prednisone, Tramadol, clomipramine,
metronidazole
Continue Carafate, IV fluids (LRS + 20 mEq/L KCl),
ampicillin IV
add milk thistle, famotidine
Fast overnight and repeat ultrasound tomorrow
Repeat CBC, panel, lytes tomorrow
Send out Lepto titers
Express bladder or catheterize to empty bladder TID
Sebastian
Day 2
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Ate chicken and drank water yesterday
Twitching stopped
Skin appears less icteric, scleral injection improved
HCT 17.7%, Hb 5.6 g/dl
Albumin 1.6 g/dl
Bili 5.4 mg/dl
Neutrophilia 20K/ul
Lytes normal
No vomiting, no melena
Urine is golden, not orange
Eating chicken and drinking
Sebastian
Ultrasound
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Liver small, mottled, hyperechoic
Liver cytology – suppurative hepatitis with cholestasis
Gall bladder wall thickened - cholecystitis
No fluid in the abdominal cavity
Plan – add Baytril & Vitamin K, monitor PCV
Sebastian
Day 3
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Vomited overnight – chicken, melena on thermometer
HCT 14.9%, Hb 4.6%
neutrophils 21.7K/ul
Albumin 1.5 g/dl
Lytes normal
Plan
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Whole blood transfusion
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Ate chicken & rice well that night, drinking water
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Continue milk thistle, ampicillin, enrofloxacin, carafate,
famotidine, Vit K, IV fluids, catheterize TID
Sebastian
Day 4
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Not feeling well, passed melena, fever 103.4F
Will not eat, licked lips when food offered
Abd US – still no evidence of perforation, but deep
ulcer seen in the duodenum
PCV 25%, albumin 1.8 g/dl, lytes normal
Plan
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Continue milk thistle, ampicillin, enrofloxacin, carafate,
famotidine, Vit K, IV fluids, catheterize TID
Sebastian
Day 5
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Fever has resolved, feels better
Eating chicken, but not rice
Urinating on own, but does not empty the bladder
Can support weight on rear legs but not front legs
If ulcer perforates, owners will not do surgery
PCV 20%, albumin 1.8 g/dl
Plan
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Continue milk thistle, ampicillin, enrofloxacin, carafate,
famotidine, Vit K, IV fluids, catheterize BID
Sebastian
Day 6
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Will not eat, no fever
When put on feet, attempts to move forward, but can
not move front legs well yet, can take a few steps
Urinating on own
neutrophils 75K, monocytes 1,100/ul
No stools passed, but melena on thermometer
Ultrasound
Sebastian
Day 6
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Will not eat, no fever
When put on feet, attempts to move forward, but can
not move front legs well yet, can take a few steps
Urinating on own
neutrophils 75K, monocytes 1,100/ul
No stools passed, but melena on thermometer
Ultrasound
Sebastian
Day 6
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Will not eat, no fever
When put on feet, attempts to move forward, but can
not move front legs well yet, can take a few steps
Urinating on own
neutrophils 75K, monocytes 1,100/ul, 6% bands
No stools passed, but melena on thermometer
Ultrasound
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Local peritonitis R Cranial abdomen
Sebastian
Plan
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Drained fluid percutaneously
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Discontinue catheterization
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Continue milk thistle, ampicillin, enrofloxacin, carafate,
famotidine, Vit K, IV fluids
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Wrap front feet to prevent abrasions from knuckling
Sebastian
Day 7
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neutrophils 38K, monocytes normal, 3% bands
HCT 20%
Albumin 1.6 g/dl, glob 5.3 g/dl
SAP >4600 U/L, ALT 1868, bili 6.7 mg/dl
Black tarry liquid stools
Plan
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Barium 5ml/lb PO
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Continue milk thistle, ampicillin, enrofloxacin, carafate,
famotidine, Vit K, IV fluids, wrap front feet
Sebastian
Sebastian
Sebastian
Sebastian
Day 8
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Owners came to visit – Sebastian ate a rib eye
Black tarry soft stools
Can walk 5-10 feet without assistance
Plan
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Continue milk thistle, ampicillin, enrofloxacin, carafate,
famotidine, Vit K, IV fluids, wrap front feet
Sebastian
Over the next 2 weeks
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Switched form injectable to oral meds
Recovered well
Recurrence of liver failure 1 year later
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Owners elected euthanasia
Inky
Inky
Handouts
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This PowerPoint – behind the blue tab
Client Drug Handouts
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Colchicine
Cyproheptadine
Lactulose
Milk Thistle
SAMe
Ursodiol
Handouts
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Client Handouts
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Cholangiohepatitis
Chronic Liver Disease
Fatty Liver
Leptospirosis
Portasystemic Shunt