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TAMU #81095
Sig: 11 yr M(c) Mixed Labrador
CC: Chronic cough
HPI: Cough and expectoration started 1
week ago
Vet found hypoalbuminemia on
routine blood work
PE: Thin but normal
TAMU #81095
PCV = 33% (35-54)
WBC = 11,100/ul (6,-17,000)
Segs = 9,102/ul (3,-12,000)
Bands = 0/ul (< 500)
Lymphs =444/ul (1,-5,000)
Platelets = 187,000/ul (200,-500,000)
TAMU #81095
BUN = 6 mg/dl (6-20)Creatinine = 0.6 mg/dl (< 2.0)Cholesterol = 51 mg/dl (120-247)Glucose = 81 mg/dl (60-120)Total protein = 5.8 gm/dl (5.5-7.5)Albumin = 1.8 gm/dl (2.5-4.4)ALT = 649 IU/L (< 110)SAP = 320 IU/L (< 130)Bilirubin = 0.1 mg/dl (< 1.0)
IS IT COST-EFFECTIVE OR
PRACTICAL TO BIOPSY THE
LIVER OF AN ASYMPTOMATIC
DOG JUST BECAUSE IT HAS
INCREASED HEPATIC
ENZYMES?
TAMU #81095
Hepatic biopsy:
SEVERE chronic hepatitis
with marked fibrosis and
scarring; early cirrhotic changes
CHRONIC HEPATITISWhat is it?
• Chronic non-septic inflammatory
disease of the liver which has many
different causes
CHRONIC HEPATITISWhat the clinician needs to know
• Breed predisposition
• Clinical signs
– chronic illness
CHRONIC HEPATITISWhat the clinician needs to know
• Breed predisposition
• Clinical signs
– chronic illness
– asymptomatic dog with lab changes
– acute illness
TAMU #149538
One year ago, they found an increased ALT, so they decided to watch and see what would happen ...
CHRONIC HEPATITISWhat the clinician needs to know
• Breed predisposition
• Clinical signs (or lack there of)
• Absolute necessity of biopsy
Drugs That Cause Hepatic Disease
Corticosteroids Acetaminophen
Phenobarbital Primidone
Sulfa drugs Carprofen
Drugs That Cause Hepatic Disease
Corticosteroids Acetaminophen
Phenobarbital Primidone
Sulfa drugs CarprofenAmiodarone Itraconazole
Ketoconazole DiazepamDoxycycline Methimazole
Azathioprine Phenytoin
Mibolerone Griseofulvin Mitotane Stanozolol
Mebendazole Clavamox
Clindamycin Cimetidine
CHRONIC HEPATITISCauses
• Drugs
– You REALLY want to catch this
BEFORE biopsy
– sometimes easy to establish cause
and effect
– sometimes hard to establish cause
and effect
Proceed w ithw orkup
N ot receiving drugs
Patientsignificantly ill
D rugs cannotbe stopped
Stop drugsR echeck A LT
over next 4 w ks
D rugs canbe stopped
Patient notsignificantly ill
R eceiving drugs
Increased A LT
Proceed w ithw orkup
N ot receiving drugs
Patientsignificantly ill
D rugs cannotbe stopped
Stop drugsR echeck A LT
over next 4 w ks
D rugs canbe stopped
Patient notsignificantly ill
R eceiving drugs
Increased A LT
Proceed w ithw orkup
N ot receiving drugs
Patientsignificantly ill
D rugs cannotbe stopped
Stop drugsR echeck A LT
over next 4 w ks
D rugs canbe stopped
Patient notsignificantly ill
R eceiving drugs
Increased A LT
Proceed w ithw orkup
N ot receiving drugs
Patientsignificantly ill
D rugs cannotbe stopped
Stop drugsR echeck A LT
over next 4 w ks
D rugs canbe stopped
Patient notsignificantly ill
R eceiving drugs
Increased A LT
CHRONIC HEPATITISCopper-associated hepatic disease
• Bedlington terrier
• West Highland white terriers
• Doberman pinschers
• Skye terrier
• Dalmations
• Labrador retrievers
CHRONIC HEPATITISCauses
• Copper intoxication
– primary (causes hepatic disease –
genetic)
• Innocent copper accumulation
– secondary (caused by hepatic disease)
TAMU #170148
Centrilobular (zone 3) deposits of copper strongly suggest that copper is the cause of the problem
CHRONIC HEPATITISTherapy for inflammation/necrosis
• Remove cause – symptomatic
– Chelate copper with d-Penicillamine
(10-15 mg/kg bid, give with food)
– Do not give zinc when administering
copper chelators
CHRONIC HEPATITISTherapy for inflammation/necrosis
• Remove cause – not symptomatic
– Decrease copper absorption with zinc
gluconate (10 mg elemental zinc/kg)
– Administer with tuna fish
– Measure blood zinc levels
• need > 200 mcg/dl to be therapeutic
• > 2,000 mcg/dl may cause hemolysis
CHRONIC HEPATITISTherapy for inflammation/necrosis
Decrease the inflammatory response
• Corticosteroids
– prednisolone (not prednisone)
– budesonide
• Cytotoxic drugs (azathioprine)
• Cyclosporine
• Ursodeoxycholic acid (15 mg/kg qd)
– A hydrophilic bile acid
– Displaces toxic, hydrophobic bile acids
• Hydrophobic bile acids are detergents
– damage hepatocyte & mitochondrial
membrane
– Food enhances bioavailability
HEPATOPROTECTIVE THERAPY
• s-adenosyl L-Methionine (SAMe)
– Human studies
• acute intrahepatic cholestasis
• alcoholic liver disease
– Veterinary studies
• healthy animals
• acetaminophen, prednisolone
HEPATOPROTECTIVE THERAPY
• Milk thistle (Silymarin)
– Silybin is the active fraction
– Antioxidant, antifibrotic, anti-inflammatory
– Effective for Amanita, aflatoxin,
acetaminophen, ethanol, ischemic
damage
HEPATOPROTECTIVE THERAPY
CHRONIC HEPATITISPrognosis
• Potentially ominous signs:
– ascites
– icterus
– severe hypoalbuminemia
– apparent cirrhosis
– hepatic encephalopathy
CHRONIC HEPATITISPrognosis
• < 4 months for those with poor
prognostic signs
• > 1.5 years for others
M ore likely to bevery im portant
A LT persistently> 3-4 X norm al
O ften notreal im portant
A LT < 3-4 X norm alOR
transiently increased
C linically normal dog w ithincreased A LT as only abnormality
M ore likely to bevery im portant
A LT persistently> 3-4 X norm al
O ften notreal im portant
A LT < 3-4 X norm alOR
transiently increased
C linically normal dog w ithincreased A LT as only abnormality
Yearly recheck
O w ner contentw ith > 99%+ certainty
B iopsy the liver
O w ner N O T contentw ith > 99%+ certainty
Look for Tumors/HepatopathyAbdom inal U ltrasound
Look for HyperadrenocorticismH istory/Physica l Exam ination
Clinically norm al dog w ith increasedSAP as only significant clinical
pathology abnorm ality
Yearly recheck
O w ner contentw ith > 99%+ certainty
B iopsy the liver
O w ner N O T contentw ith > 99%+ certainty
Look for Tumors/HepatopathyAbdom inal U ltrasound
Look for HyperadrenocorticismH istory/Physica l Exam ination
Clinically norm al dog w ith increasedSAP as only significant clinical
pathology abnorm ality
Yearly recheck
O w ner contentw ith > 99%+ certainty
B iopsy the liver
O w ner N O T contentw ith > 99%+ certainty
Look for Tumors/HepatopathyAbdom inal U ltrasound
Look for HyperadrenocorticismH istory/Physica l Exam ination
Clinically norm al dog w ith increasedSAP as only significant clinical
pathology abnorm ality
TAMU #96276
Sig: 4 yr M Cocker Spaniel
CC: Swollen abdomen
HPI: Dark yellow urine and depression
were first noted by owners 2
days ago
Today the dog has an obviously
swollen abdomen
PE: Depressed and has ascites
TAMU #96276
BUN = 57 mg/dl (8-29)Creatinine = 2.4 mg/dl (< 2.0)Sodium = 128 mEq/L (138-148)Potassium = 4.9 mEq/L (3.5-5.0) Total protein = 6.5 gm/dl (5.5-7.0)Albumin = 2.0 gm/dl (2.5-4.4)ALT = 72 IU/L (< 130)SAP = 128 IU/L (< 147)Bilirubin = 1.6 mg/dl (< 0.8)
TAMU # 72927
Sig: 9 yr M(c) Cat 6 kg
CC: Weight loss & vomiting
HPI: Poor appetite & vomiting bile for
6 weeks; has lost 2.3 kg
ALT = 202 U/L
SAP = 427 U/L
PE: No significant findings
TAMU # 72927
Cytology of liver (ultrasound guided):
“no cytologic evidence of active
inflammation or neoplasia … mild
hepatic lipidosis”
TAMU # 72927
Histopathology:
“Moderate to severe multifocal
lymphocytic cholangiohepatitis with
cholestasis; mild hepatic lipidosis”
“Diagnostic Accuracy of Tru Cut
Needle Biopsy Compared to
Wedge Biopsy of the Liver” by
Cole et al, JAVMA 220:1483, 2002
100 dogs and 22 cats
51.6% discordance between results
Hepatic Biopsy
GUIDANCE TYPE OF BIOPSY
Blind Fine needle aspirate
Ultrasound Core needle
Laparoscopy Wedge
Surgery
TAMU #162500
Abdominal U/S: “The liver, pancreatic
region, GI tract, kidneys and adrenals
were unremarkable.”
TAMU #139804
Abdominal U/S: “The liver and spleen
were unremarkable. ... Essentially
normal abdominal ultrasound.”
TAMU #128604
Abdominal U/S: “A sonographic
examination of the abdomen was
performed and revealed no significant
abnormal findings”
TAMU #168184
Abdominal U/S: “... sludge within the
gall bladder. This was organizing and
probably the early development of a
cholelith. The remainder of the liver was
considered normal ... Changes in the gall
bladder consistent with sludge and
possibly early cholelith development.
Otherwise, normal abdomen. ”
TAMU #147332
Abdominal U/S: “The liver appeared to
be of normal size, texture and
echogenicity. ... Essentially normal
abdominal ultrasound.”
Ultrasound and the Liver
• 40% (dog) to 60% (cat) accurate in
diffuse hepatic diseases
• Cannot distinguish benign from
malignant nodules