Chronic Hepatitis Consensus Statement Flashcards
What is the WSAVA definition of chronic hepatitis?
Key histologic features: lymphocytic, plasmacytic, or granulomatous inflammation (portal, multi focal, zonal, panlobular) or some combination, along with hepatocyte cell death and variable severity fibrosis and regeneration
What is lobular dissecting hepatitis?
Lobular inflammation and disruption of hepatic cords by fine fibrous septa, hepatocyte necrosis, and marked ductular reaction
What is the most common cause of chronic hepatitis?
Idiopathic
What are potential infectious etiologies that may result in chronic hepatitis?
No strong evidence for underlying viral etiology
Other infectious causes with sporadic associations with chronic hepatitis:
Leptospirosis MAY induce a chronic pyogranulomatous response after acute infection
Bacillus pilliformis, Helicobacter canis, Bartonella spp. — have been identified in dogs with CH, but minimal evidence to suggest that they CAUSE CH
Ehrlichia canis
Babes is - causes non-suppurative hepatitis
Anaplasma - subacute hepatitis
Leishmania - causes granulomatous inflammation, chronic hepatitis
Other: Neospora, toxoplasma, Sarcocystis, hsitoplasma, mycobacteria, schistosomiasis, visceral larval migrants
What are potential drugs/ toxins that may results in chronic hepatitis?
Drugs/ toxins more commonly cause acute liver injury but cirrhosis and CH can be potential sequelae
E.g. phenobarbital, primidone, phenytoin, lomustine — all of these can cause chronic hepatitis
Other drugs: carprofen, oxibendazole, amiodarone, aflatoxin, cycasin - more commonly cause acute hepatopathy
Herbal and dietary supplements
MOST COMMON - hepatic copper excess - copper associated chronic hepatitis
What is the genetic mutation that causes copper hepatitis in Bedlington Terriers?
Autosomal recessive deletion in exon 2 of ATP7B associated protein (COMMD1)
What genetic mutations may result in copper hepatopathy in Labrador retrievers?
ATP7B gene - predisposes to copper accumulation
ATP7A gene - intestinal copper transporter, which protects against copper accumulation
What is the copper concentration that triggers copper hepatitis?
This is unknown
What is an acute presentation of copper hepatitis?
Acute Neuro inflammatory crisis - causes Coombs negative hemolytic anemia
Copper accumulation in the kidneys associated with underlying copper storage disease can cause what?
Acquired Franconia like syndrome
What are the three main diagnostic criteria for confirmation of copper hepatitis/hepatopathy?
Histological evidence of chronic hepatitis associated with hepatic copper accumulation - copper typically centrilobular, or in zone 3
histochemical copper straining showing hepatocyte copper accumulation in centrilobular area
Hepatic copper with copper concentrations usually >1000 mcg/g dw liver
What is considered the “grey zone” of quantitative hepatic copper concentrations?
Between 600 and 1000 mcg/g dw liver
What is alpha 1 anti trypsin deficiency (AAT) ? Which breeds are predisposed?
It is a metabolic condition caused by abnormal hepatic processing of alpha 1 anti trypsin. This causes hepatocyte retention of abnormally folded proteins, causing chronic hepatitis.
Breeds - American and English Cocker Spaniels
What is erythropoietin protoporphyria? Which breed has this disease been reported in?
Disorder of porphyrin metabolism, results in accumulation of porphyrins in hepatocytes
It has been reported in GSD
What age range and what breed does lobular dissecting hepatitis typically present?
Younger age
Male
Cocker spaniel predisposition
Ultrasonographically, is the liver typically HYPO or HYPERechoic to the spleen?
Order of hyper to hypoechoic = Spleen —> liver —> kidney
Liver should be hypoechoic to the spleen
How many portal triads are needed for appropriate evaluation of hepatic architecture?
12-15 portal triads
How many minimum laparoscopic or surgical specimens should be obtained during liver biopsy and how should these specimens be allocated?
Minimum 5
1 piece for copper
1 piece for aerobic and anaerobic culture
3 pieces for histopath
What is the main histopathologic hallmark of disease chronicity? What changes indicate end stage disease?
Fibrosis
Final fibrosis stage/ indicator of end stage disease - prominent bridge septa and nodular regeneration of hepatocytes
What are special stains to evaluate for copper?
Rhodanine or rubes if acid
What does periportal copper accumulation indicate?
Nonspecific - may indicate cholestasis/ be secondary to primary process
What is the gold standard for tissue copper quantification? What other tests of copper can be done if gold standard is not available?
Atomic absorption spectroscopy - gold standard
Other - digital quantification of copper using scanning of rhodanine stained tissue
If pyogranulomatous inflammation is noted on histopathologic, what additional testing should be performed?
Infectious disease testing
In dogs with copper hepatopathy, how long should copper be restricted? How much dietary copper is recommended? Can this be done in place of chelation?
Life long
< 0.12 mg/100 kcal of copper
No it can’t be done in place of chelation
What is the mechanism of action of D-penicillamine?
Copper chelation of choice in copper hepatopathy
Binds hepatic copper to be eliminated in urine and increases metallothionein in hepatocytes (detoxifies intracellular copper) and enterocytes (facilitates fecal elimination). It also has mild anti- inflammatory and anti-fibrotic properties
How long should treatment with D-penicillamine be continued in the case of copper hepatopathy?
Treat for one month beyond ALT resolution, then stop
Should D. Penicillamine and zinc be given together?
NO you idiot, their effects negate each other
What are alternative second line copper chelating agents?
Choline tetrathiomolybdate
Trientene
What are poor prognostic indicators in a dog with chronic hepatitis?
Hyperbilirubinemia PT/PTT prolongation Hypoalbuminemia Ascites Extent of fibrosis on biopsy
In a dog (or cat) with underlying hepatic dysfunction, what is a potential consequence of administering a blood transfusion?
Hepatic encephalopathy - stored blood contains products of anaerobic metabolism/ protein breakdown, may provoke HE event
