24. Chronic hepatitis, familiar liver diseases in dogs Flashcards

1
Q

Chronic Hepatopathy in general?

A

CHRONIC HEPATOPATHY IN GENERAL

Toxins; Drugs → Chronic liver failure → “End-stage liver”

Liver fibrosis: Reversible; Ø Regenerative nodule

Liver cirrhosis: Irreversible; Fibrosis + Regenerative nodules

Clinical Signs

§ Anorexia § PU/PD

§ Weight loss § Icterus

§ Ascites § Coagulopathy

CNS signs (HE)

Lab. D

§ ↑ ALT & ALP § ↑ BA & NH3

§ ↓ Albumin & BUN § Microcytosis

Biopsy

§ Piecemeal necrosis: Necrosis of hepatocyte layer adjacent

to portal tract

§ “Bridging” necrosis: Tracts of necrosis across the hepatic

lobule from portal areas → Central veins

§ Chronic active hepatitis: Periportal inflammation +

Piecemeal necrosis

§ Lobular dissecting hepatitis: Lobular hepatitis associated

with dissecting tracts of fibrosis (poodle)

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2
Q

Chronic Hepatitis?

A

Chronic Hepatitis

The most common grouping of liver disease in dogs

Characterised by mononuclear/mixed infiltrate in the liver with accompanied periportal necrosis + fibrosis

Leads to hepatic cirrhosis

PREDISPOSED

§ Bedlington terrier § Dalmatian

§ Doberman pinscher § Skye terrier

§ White West Highland terrier § Poodle

§ Cocker spaniel § Labrador

PATHOPHYSIOLOGY

Poorly understood

Causes

§ Toxins/drugs

§ Copper: Causes necrosis → Disrupts architecture

§ Infective agents: Infectious canine hepatitis;

Leptospirosis; Helicobacter

§ Immune-mediated

§ Unknown/Idiopathic (ICH)

Idiopathic chronic hepatitis: CAH with unknown reason

Lobular dissecting hepatitis: Young poodles

CLINICAL SIGNS

§ Anorexia § PU/PD

§ Weight loss § Ascites

§ Vomiting § Jaundice

§ Weakness § Depression

§ Mild, varying GI signs

LAB. D

§ ↑↑↑↑↑ ALT § ↑↑ ALP

§ ↓ Albumin § ↑ BA

§ Non-regenerative anaemia § ↑ Br

DIAGNOSIS

Biopsy: Definitive diagnosis

Histopathology; Culture & sensitivity

Ultrasound

Normal/hyperechogenic; May appear small; Nodular in cirrhosis

cases

FNA: Not relevant

TREATMENT

Immunosuppressive therapy; Ø Glucocorticoid therapy

Indications: Persistent liver failure; Piecemeal necrosis; Bridging

necrosis; Fibrosis; Periportal infiltration

Treat the underlying cause: Infection; Drugs; Toxins; Copper

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3
Q

Copper- Caused Chronic hepatitis(CUCH)?

A

COPPER-CAUSED CHRONIC HEPATITIS (CUCH)

Primary: Centrilobular

Secondary: Periportal

Copper is stored & encapsulate in hepatocyte lysosomes →

Inaccessible by chelating drug

Rupture of lysosomes → Free IC copper → Necrosis → CH

When copper > 2000ppm: Lysosome rupture → Clinically significant

Diagnosis

§ Histology (centrilobular copper accumulation)

§ Histochemical copper staining

§ Copper >1000μg/g in the liver

Treatment

§ Chelating drugs: Actively bind extracellular copper

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4
Q

Copper storage disease in bedlington terrier?

A

Familiar Liver Disease In Dogs

COPPER STORAGE DISEASE IN BEDLINGTON TERRIER

Primary copper storage disease; Progressive copper accumulation

resulting from failure of normal hepatic biliary excretion → CH

Homozygous genotypes

Asymptomatic form

Only affects young animals; Copper in the lysosomes

↑ ALT; Ø Structural damage

Acute form

Young adults; Rare

Progressive copper accumulation

Acute hepatic necrosis; Haemolytic anaemia

Clinical signs: Lethargy; Vomiting; Depression; Anorexia

Poor prognosis; Death within 2-3 days

Chronic form

Young-middle aged

Early stages of chronic progressive form; Focal-random

hepatic necrosis; ↑↑↑ ALT; Ø CSx

Middle-aged

Chronic hepatitis; ↑ ALT

CSx: Weight loss; Cachexia; Ascites; Jaundice; HE;

Cirrhosis

Heterozygous genotypes: Transient ↑ copper

Autosomal recessive genotype?

Screening testing to identify affected carriers – Removal from

breeding

§ Screening for specific gene mutations

§ Screening using microsatellite marker

§ Biopsy → Histology

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5
Q

Copper storage of Dobermans?

A

COPPER STORAGE OF DOBERMANS

Dobermans are similar to Bedlington terriers but have two types of

chronic hepatitis → Primary Cu toxicosis + CuCH; Developing at a

much lower level than in Bedlingtons

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6
Q

Treatment of abnormal copper storage diseases?

A

TREATMENT OF ABNORMAL COPPER STORAGE

DISEASES

Normal levels of Copper are <400μg/g

Copper chelators

D-penicillamine (not to be used with Zn):

§ ↓ Copper in the liver

§ ↑ Liver metallothionine (a metal binding protein)

Zn-salts (not to be used with chelators or D-penicillamine)

§ ↓ Intestinal absorption of copper

§ Good for cases of cholestasis

Antioxidants

Protection from oxidative injury from copper

§ SAMe

§ Vit. E

Sillymarin

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7
Q

Lobular dissecting hepatitis?

A

LOBULAR DISSECTING HEPATITIS

Unknown cause; Idiopathic

Young > Old; Poodle

Thought to be a response of the liver to a variety of insults whilst at a juvenile stage

Portal hypertension → Ascites; APSS

Lymphocytes, plasma cells & macrophages are scattered throughout

the hepatic lobule

Bands of collagen & reticulin fibres around hepatocytes

Pathology of liver: Shrunken; Smooth; Hyperplastic nodules

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8
Q

Non-Specific reactive hepatitis?

A

NON-SPECIFIC REACTIVE HEPATITIS

Consequence of extrahepatic diseases

Mildly elevated liver enzyme parameters: ↑ALT; ↑↑ALP

Ø Necrosis

CSx: Hypoxia; Fasting; Anorexia

Causes

§ Metabolic: Cushing’s; Hypoadrenocorticism; DM;

Hypo-/Hyperthyroidism

§ GI: IBD; PLE

§ Other: Acute pancreatitis; Sepsis; IHA; FIP;

Toxoplasma

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9
Q

Nodular hyperplasia?

A

NODULAR HYPERPLASIA

Unknown cause

Old dogs > Young dogs

Usually seen as a post-mortem finding

↑-↑↑↑ ALT; ↑-↑↑↑ ALP

Diagnosis

Ultrasound: Multiple macroscopic nodules

Histopathology

§ Vacuolised hepatocytes

§ Normal lobular structure

§ Ø Fibrosis; Ø Necrosis; Ø Inflammation

§ Growing nodules compress the surrounding parenchyma

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10
Q

Treatment of chronic Hepatopathies?

A

Treatment Of Chronic Hepatopathies

Prednisolone (as a treatment of idiopathic chronic hepatitis)

§ Immunosuppressive dose

§ Improvement of necrotic inflammation & coagulopathy

§ Decrease of inflammation

Other immunosuppressants

§ Glucocorticoids: Effective first-line treatment

§ Dexamethasone (portal hypertension; ascites)

§ Cyclosporine

§ Azathioprine (max. 14 day course)

Choleretic (stimulates bile production by the liver)

§ UDCA (Ursodeoxycholic acid)

§ Hepatoprotective; Anti-inflammatory; Antifibrotic;

Immunomodulator

§ Helps the elimination of toxin

§ Necro-inflammatory disease; Cholestatic disease

Antifibrotic

§ Colchicine

§ Prednisolone

§ D-Penicillamine

§ Vit. E

§ UDCA

Antioxidants

§ Vit. E § Vit. C

§ S-adenosylmethionine (SAMe) § Silymarin

§ N-acetylcysteine (NAC) § Zn

§ Coenzyme-Q

Treatment of coagulopathy: Plasma transfusion; Vit. K1

Treatment of Ascites: Spironolactone; Furosemide;

Abdominocentesis

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