tamu#81095

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)

TAMU #81095

Abdominal ultrasound:

“No significant findings”

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



• Clinical signs

– chronic illness

– asymptomatic dog with lab changes

– acute illness

IMPORTANCE OF THE

WORD “CHRONIC”


TAMU #149538

One year ago, they found an increased ALT, so they decided to watch and see what would happen ...



• Clinical signs (or lack there of)

• Absolute necessity of biopsy

WHAT DO YOU DO

AFTER DIAGNOSING

CHRONIC HEPATITIS?

Drugs That Cause Hepatic Disease

Corticosteroids


Corticosteroids Acetaminophen

Phenobarbital Primidone

Sulfa drugs Carprofen


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

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


• 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


Decrease the inflammatory response

• Corticosteroids

– prednisolone (not prednisone)

– budesonide

• Cytotoxic drugs (azathioprine)

• Cyclosporine

HEPATOPROTECTIVE THERAPY

• What this therapy does NOT do ...

• What this therapy does do ...

• 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


• s-adenosyl L-Methionine (SAMe)

– Human studies

• acute intrahepatic cholestasis

• alcoholic liver disease

– Veterinary studies

• healthy animals

• acetaminophen, prednisolone


• Milk thistle (Silymarin)

– Silybin is the active fraction

– Antioxidant, antifibrotic, anti-inflammatory

– Effective for Amanita, aflatoxin,

acetaminophen, ethanol, ischemic

damage


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

WHAT ABOUT THE

“NORMAL” DOG THAT HAS

AN INCREASED ALT?

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

WHAT ABOUT THE

“NORMAL” DOG THAT JUST

HAS AN INCREASED SAP?

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

WHAT ABOUT SCOTTISH

TERRIERS?

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)

Hepatic Biopsy

GUIDANCE TYPE OF BIOPSY

Blind Fine needle aspirate

Ultrasound

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”

Hepatic Biopsy



Ultrasound Core needle

“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



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

Modified laparoscopy

JAVMA 187:1032, 1985

Sterile

Not sterile

Sterile towel

tamu#81095

Documents

hepatic biopsy

hepatic diseasetamu

hepatic enzymes

chronic coughhpi

deposits of copper

severe chronic hepatitiswith

normal tamu

zinc gluconate