hepatobiliary 2: acute hepatitis

Question 1

infectious causes of acute hepatits?

Answer 1

Canine adenovirus-1
Leptospirosis
Clostridium spp.
Ehrlichia canis

Question 2

toxins that can cause acute hepatitis

Answer 2

• Mycotoxins, aflatoxicosis
• Blue green algae (cyanobacteria)
• Amanita mushrooms
• Xylitol
• Organic solvents
• Cycad / sago palms

Question 3

deugs that can cause acute hepapitis

Answer 3

Carprofen
Acetaminophen (cats&raquo_space; dogs)
TMS
Azathioprine
Diazepam (oral – cats)
Ketoconazole
Methimazole (cats)
Antiepileptics (phenoparbital, zonisamide)

Question 4

Acute Hepatic Injury: Presentation

Answer 4

Clinical signs related to hepatic cell necrosis & inflammation
* Non-specific: anorexia, vomiting, PU/PD
* More specific: abdominal pain, ascites
* Liver-specific: icterus

• Signs of coagulopathy, hepatic encephalopathy can be present

Question 5

Acute Hepatic Injury: Diagnosis - biochem and lab findings

Answer 5

Biochemical profile:
* Marked elevations ALT, AST occur early in the process
* Signs of cholestasis often present
* Possibly azotemia (pre-renal, or renal from shared etiology)

Otherlaboratoryfindings
* Anemia (blood loss, other causes)
* Coagulopathy
* Signs of DIC

Question 6

Leptospirosis testing methods

Answer 6

• Point-of-care antibody tests ( Zoetis Witness)
• PCR
• Microscopic agglutination test (MAT)

Question 7

Point-of-care antibody tests ( Zoetis Witness) for lepto; what may occur in acute disease?

Answer 7

• IgM Can be negative in acute disease

Question 8

PCR lepto test; what do we sample? when? cuation with antibiotics?

Answer 8

• Performed on blood and urine
• Typically positive in blood in first 10 days of infection, urine thereafter
• Antibiotics cause negative result

Question 9

lepto Microscopic agglutination test (MAT); how does it work/ what is detected? how does vaccination affect this?

Answer 9

• Antibodies to several serovars
• 4-fold increase in acute and convalescent (2-weeks later) supportive of diagnosis
• Vaccination can cause positive titres

Question 10

Serovars covered in North American leptospirosis vaccination

Answer 10

• ‘CPIG’
• Canicola, Pomona, Icterohaemorrgiae, Grippotyphosa

Question 11

Acute Hepatic Injury: Diagnosis - what do we see with imaging?

Answer 11

Abdominal imaging
* Liver can be large, presence of ascites
* Hepatic parenchyma diffusely altered echogenicity
* Ultrasound can be normal

• Ultrasound findings not specific, do not define extent of injury

Question 12

Acute Hepatic Injury: Treatment

Answer 12

Treatment of underlying cause, if known
* Toxin: gastric decontamination
* Empirical treatment Leptospirosis if risk in your area (doxu

Liver supportive treatment
* Antioxidant (SAMe and others, N-acetylcysteine as an IV option)
* Ursodiol if cholestatic

Intensive care support
* GIulceration, coagulopathy

Question 13

why is the liver prone to oxidative damage?

Answer 13

• Central role in metabolism of drugs, toxins
• Large population of macrophages (Kuppfer cells)

Question 14

purpose of glutatione? when may it be reduced?

Answer 14

• Essential anti-oxidant in hepatocytes
• Reduced levels found in bile duct obstruction, lipidosis, inflammatory liver disease

Question 15

is oxidative injury often important in canine /. feline hepatobiliary disease?

Answer 15

• Oxidative injury likely important in canine & feline hepatobiliary disease

Question 16

Commonly used anti-oxidants for liver

Answer 16

• SAMe
• Silymarin (Milk thistle)
• Vitamin E
• N-Acetylcysteine

SAMe & silymarin available together in some commercial products

Question 17

reccomended antioxidant for liver support, and why

Answer 17

Recommend to use veterinary grade SAMe products
* Over the counter products might not contain appropriate amounts despite label

Question 18

Evidence-based indications for antioxidants for liver support, for amanita, Acetaminophen toxicity, aflatoxins, Lomustine

Answer 18

• Amanita toxicity – silymarin improved outcomes
• Acetaminophen toxicity, aflatoxins – N-acetylcysteine improved outcomes
• Lomustine – SAMe/silymarin protective

Question 19

Suggested indications for anti-oxidants for liver

Answer 19

• Acute liver injury
• Canine chronic hepatitis
• Feline hepatic lipidosis

Question 20

can or should we combine antioxidants for liver treatments?

Answer 20

• Ideal agent / combination of agents unknown
  > Generally safe

Question 21

Choleretics; what do they do?

Answer 21

• Modulates bile acid pool (less toxic to hepatocytes)
• Anti-inflammatory and anti-oxidant properties

Question 22

• Only absolute contraindication for choleretics? when are they often used?

Answer 22

Only absolute contraindication is complete biliary obstruction
* Often added to patients with cholestasis as part of their condition * Limited evidence

Question 23

choleretic which is given for liver support

Answer 23

Ursodeoxycholic acid (ursodiol)
* Synthetic hydrophilic bile acid

Question 24

what animal is hepatic nodular hyperplasia common in? how many nodules?

Answer 24

• Hepatic nodular hyperplasia very common in older dogs
• Single o rmultiple nodules

Question 25

nodular hyperplasia presentation; enzymes, signs

Answer 25

Presentation * Mild to moderate elevations in liver enzymes, typically found incidentally * No clinical signs

Question 26

Nodular Hyperplasia; can we see it on ultrasound? what type of liver change is this?

Answer 26

Can appear on ultrasound as a neoplastic process but is a benign, regenerative change

Question 27

CASE: * Problem list: * Pyrexia * Icterus * Recent decrease appetite, now anorexia * Decreased MCS and BCS * Dehydrated * Chronic vomiting > what are our initial plans?

Answer 27

* Biochemical profile * Complete blood count * Urinalysis * FeLV/FIV

Question 28

Cholangitis - what is this? where can it extand? what animal is this common in?

Answer 28

Inflammation of the biliary tract * Can extend into hepatic parenchyma (“cholangiohepatitis”) * Cholangitis affects cats >> dogs

Question 29

Feline Cholangitis - what liver values do we expect to be high?

Answer 29

* Serum ALP, GGT * Serum bilirubin * (ALT, AST elevation if cholangitis extends into hepatic parenchyma) >BUT remeber cats have such short enzyme half lives that we may not see these elevated values

Question 30

why may serum ALP and GGT be elevated? how do these enzymes differ in cats vs dogs?

Answer 30

* Biliary epithelium react to inflammation, other stimuli * Increased in intrahepatic or extrahepatic cholestasis, drug effect (dogs) * Shorter half-life in cats vs dogs

Question 31

what can cause a rise in serum bilirubin levels? what will PCV look like? what mix will we see in most hepatobiliary disease?

Answer 31

* Pre-, hepatic, and post-hepatic causes * Normal PCV = intra- or extra-hepatic cholestasis present * A mix of conjugated and unconjugated bilirubin in most hepatobiliary diseases

Question 32

diseases that are commonly concurrent with feline cholangitis? why?

Answer 32

* Concurrent pancreatitis and/or intestinal disease common > “Triaditis” Shared pathophysiology: * Anatomy: pancreatic & bile duct proximity; sphincter of Oddi spasm in IBD * Common triggers / causative agent * Likelymultifactorial

Question 33

Neutrophilic (Suppurative) Cholangitis - what is the likely cause of this? is it usually acute or chronic?

Answer 33

* Likely ascending bacterial infection from intestine > E.coli, Streptococcus, Klebsiella, Pseudomonas, Enterococcus, Clostridium, etc > Neutrophilic inflammation of bile lumen, ducts, edema * Typically acute in nature > A more chronic, mixed inflammatory stage also recognized

Question 34

Neutrophilic Cholangitis: Presentation - what signalment? clinical signs?

Answer 34

* Any signalment of cat, but typically young to middle-age * Clinical signs usually <1 month > Pyrexia, lethargy, icterus, other non-specific signs > Signs of pancreatitis or intestinal disease can be present and overlap

Question 35

Neutrophilic Cholangitis: Diagnosis - labwork and ultrasound results?

Answer 35

* Labwork and imaging results not sensitive or specific * Often: > Neutrophilic inflammation on CBC > Elevated bilirubin, ALT (sometimes ALP) > Labwork can be normal * Ultrasound: > Enlarged liver, dilated biliary tracts, gall bladder debris might be present > +/- Pancreatitis, intestinal disease

Question 36

Neutrophilic Cholangitis: how do we get a difinitive diagnosis? risks and contraindications? - do we have some other options that might be helpful, aside from imaging, labwork?

Answer 36

Definitive diagnosis requires cholecystocentesis & bile culture * Risks (overall low): GB rupture, hemorrhage * Contraindicated if noted GB wall devitalization * Liver fine needle aspirate > Neutrophilic inflammation, non-specific * Hepatic biopsy > Portal and biliary duct neutrophilic inflammation

Question 37

Neutrophilic Cholangitis - can we always get a diagnosis? how do we often proceed?

Answer 37

can be difficult to get difinitive diagnosis * Often: empirical treatment after presumptive diagnosis

Question 38

when is sampling for neutrophilic cholangitic contraindicated?

Answer 38

* Sampling contraindicated if uncontrolled coagulopathy

Question 39

Neutrophilic Cholangitis: Treatment

Answer 39

* Antibiotics for 4-6 weeks: ideally based on culture and sensitivity * Empirical choices targeting gram positive & negative, aerobe and anaerobe (E coli most common); bile secretion; bactericidal > Fluoroquinolone (+/- potentiated penicillin/ clindamycin) > Penicillin + metronidazole > No enrofloxacin in cats! (Prado, marbofloxacin appropriate) * IV antibiotics if signs of sepsis or systemic illness * Hospitalization for IV fluids, nutritional support usually required * Anti-emetics, appetite stimulants * Vitamin K if coagulopathy (plasma in severe cases) * Consider: > S-adenosylmethionine, silybin, and ursodeoxycholic acid (ursodiol) * Treatment for concurrent disease (e.g., pancreatitis) > Analgesia with opioids > If signs of intestinal disease, eventually consider diet suitable for IBD

Question 40

Neutrophilic Cholangitis - what should we consider doing prior to discontinuing antibiotic treatment? what other disease might we want to investigate?

Answer 40

* Consider rechecking hepatic values prior to discontinuing antibiotics * Patients might require further investigation for other diseases > IBD, chronic pancreatitis

Question 41

Neutrophilic Cholangitis: Prognosis

Answer 41

* Most cats recover with treatment, recurrence not common * Concurrent disease a factor in prognosis * Complications rare > GB obstruction with cholelith, abscessaction