24. Chronic hepatitis, familiar liver diseases in dogs Flashcards
Chronic Hepatopathy in general?
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)
Chronic Hepatitis?
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
Copper- Caused Chronic hepatitis(CUCH)?
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
Copper storage disease in bedlington terrier?
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
Copper storage of Dobermans?
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
Treatment of abnormal copper storage diseases?
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
Lobular dissecting hepatitis?
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
Non-Specific reactive hepatitis?
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
Nodular hyperplasia?
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
Treatment of chronic Hepatopathies?
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
