Hepatobiliary diseases in felines are common causes of morbidity. Two common inflammatory hepatopathies in cats are cholangiohepatitis and lymphocytic portal hepatitis. Neutrophilic cholangitis is more common in cats than dogs and can progress to bile duct rupture, necrosis or abscesses. Ultrasonography and fine needle aspiration are useful diagnostic tools for hepatobiliary diseases in cats. Liver failure can result from conditions like hepatic lipidosis, cholangiohepatitis, toxins or portosystemic shunts and results in non-specific symptoms like vomiting, weight loss and jaundice.

1. Submitted to : Dr Aamtul Muhi
submitted by :Nadia mushtaq
Tracking programme(feline medicine)
Hepatobiliary diseases in felines
Special reference to liver failure and jaundice

2. Feline Inflammatory/Infectious Hepatic
Disease
• Feline inflammatory and infectious hepatobiliary diseases are
common causes of morbidity and less frequent mortality in cats.
• Two common feline inflammatory hepatopathies include
cholangiohepatitis (acute [suppurative] and chronic [non-
suppurative or mixed]) and lymphocytic portal hepatitis.
• Infectious hepatobiliary diseases, diagnosed less often,
remain an important differential diagnosis when formulating
treatment plans.

3. Neutrophilic Cholangitis/Cholangiohepatitis
• Neutrophilic cholangitis (NC) is more common in cats than in dogs and is subclassified into acute
neutrophilic cholangitis (ANC) and chronic neutrophilic cholangitis (CNC).The proposed
pathogenesis is an ascending intestinal bacterial infection
• Histologically, neutrophils are noted within the bile duct lumen, closely associated with the bile duct or
between the biliary epithelial cells. If the inflammation extends beyond the limiting plate and into the
hepatic parenchyma, the diagnosis is cholangiohepatitis (CH).
• Progressive disease can result in bile duct rupture with bile leakage, necrosis or abscesses.
• Common clinical signs included lethargy, vomiting, weight loss and decreased appetite.
• Physical examination abnormalities are not common, but include fever (22%), icterus (34%) and
hepatomegaly (21%).
• Abnormalities on complete blood counts (CBCs) are detected in less than half of cats with NC and,
when present, include leukocytosis (39%), band neutrophils (33%), and anaemia (34%).
• Variable increases in aspartate transaminase activity (AST) ,alanine transaminase (ALT), alkaline
phosphatase activities (ALP) and gamma-glutamyl transferase (GGT) have been noted

4. Ultrasonography (US) and US-Guided Fine-Needle Aspiration (FNA)
• Hepatobiliary abnormalities are frequently detected during abdominal US examination in
cats with NC, including hyperechoic parenchyma with or without hepatomegaly, bile duct
or gallbladder distension and increased gallbladder sediment
• Other abnormalities commonly noted in cats with NC are pancreatic enlargement,
hypoechoic parenchyma and hyperechoic peri-pancreatic parenchyma.
Gastrointestinal (GI) tract abnormalities include thickened walls and fluid distension.
• US does permit guided percutaneous collection of samples for cytologic or histologic examination.
• FNA with cytologic examination has distinct advantages and limitations in evaluating cats with
hepatic disorders.
• It is cost-effective, expedient, relatively straight-forward to perform, provides quick
diagnostic information as compared with liver histopathology, complications are
uncommon, needed pre-procedure testing is limited (coagulation is not typically required)
and can usually be performed without anaesthesia or sedation.

5. Lymphocytic Cholangitis
• The signalment, clinical signs and diagnostic evaluation for lymphocytic cholangitis (LC)
is reviewed in the “Neutrophilic Cholangitis/Cholangiohepatitis” section with a few
exceptions. In addition to nausea, vomiting, lethargy (listlessness) and inappetence, cats
with LC often develop gradual weight loss and jaundice
• In contrast to NC/CH, the most consistent biochemical abnormality in cats
with LC is hypergammaglobulinemia; however, increases in hepatic enzyme activities and
total bilirubin are detected in some cats.
• The pathogenesis of LC was thought to be the consequence of chronic bacterial infection in
cats with NC.
• Rather, immune-mediated mechanisms have been proposed.
• Histologically, LC is characterized by dense aggregates of lymphocytes surrounding bile
ducts but not invading the biliary epithelium. Lymphocytes may be detected in the bile lumen
(in contrast to NC).
• Bile duct targeting, ductopenia, peribiliary fibrosis, portal B-cell aggregates, portal
lipogranulomas and polyclonal TCR are features of LC.

6. Infectious Hepatobiliary Diseases
Bacterial Infection
• Compared to inflammatory hepatobiliary diseases, primary feline infectious hepatobiliary diseases are
reported less frequently.
• The proposed pathogenesis is a secondary infection due to ascending intestinal bacteria.
• Both micro- and macrohepatic abscesses have been reported in cats. Other pathogenesis concepts
include trauma, alterations in blood flow, liver lobe torsions, extrahepatic infection, sepsis, clinically
immunocompromised states and neoplasia.
• Aerobic and anaerobic bacterial culture results in cats with hepatic abscesses are similar to those of
cats with NC/CH with clinically rare isolates being Klebsiella, Listeria, Salmonella, Brucella, Yersinia
pseudotuberculosis, Actinomyces, Nocardia and Pasteurella.
• Chronic cholangitis has been associated with liver fluke infestation from the Platynosomum group
Platynosomum Infections

7. Viral Infections
Feline Leukemia Virus (FeLV)
Feline Calicivirus (FCV)
Feline Infectious Peritonitis (FIP)
Feline Immunodeficiency Virus (FIV)
Fungal Infection
The fungal organisms Histoplasma capsulatum , Coccidioides
immitis , Blastomyces dermatitidis, Aspergillosis sp.,
Cryptococcus sp., and Sporothrix schenckii can, rarely, cause
primary or disseminated infectious hepatobiliary disease.

8. Hepatic Vascular Anomalies
• Portosystemic shunts (PSSs) are vascular anomalies that connect the portal vein to the systemic
circulation, bypassing the hepatic sinusoids and liver parenchyma
• Normally, venous blood draining the spleen, pancreas, stomach, and intestine enters the portal
vein, perfuses the liver through the sinusoidal network, and drains through the hepatic veins into
the caudal vena cava (CVC). Portal blood carries many substances to the liver, including trophic
hormones (intestinal and pancreatic), nutrients, bacterial products, and intestinal-derived
toxins.The fetal liver has limited function to process these products, and a large shunting vessel,
the ductus venosus, bypasses the hepatic circulation as a protective mechanism.This fetal vessel,
located on the left side of the liver, normally closes by 3-10 days of age.Closure is initiated by
blood pressure changes after umbilical venous flow ceases; thromboxane or various adrenergic
compounds can stimulate contraction of the musculature of the ductus venosus and might aid in
the vessel's closure.If the ductus venosus remains patent, or other congenital communications
exist, a PSS results. When blood bypasses the liver, trophic factors (particularly insulin and
glucagon) are not available to encourage hepatic growth, resulting in poor hepatic development,
deficient protein production, reticuloendothelial dysfunction, altered fat and protein
metabolism, hepatic atrophy, and eventually liver failure.
• Clinical signs are associated with the volume and origin of blood bypassing the liver, resulting in
impaired hepatic function, hepatic encephalopathy (HE), chronic gastrointestinal (GI) signs, lower
urinary tract signs, coagulopathies, and delayed growth.

9. Toxins Implicated in Hepatic Encephalopathy

10. Types of Hepatovescular disease
Congenital (CPSSs)
• Macrovascular portosystemic shunts
• Intrahepatic (IHPSSs)
• Extrahepatic (EHPSSs)
• Primary portal vein hypoplasia (PVH)
• PVH with portal hypertension (e.g., noncirrhotic portal hypertension [NCPH])
• PVH without portal hypertension (formerly microvascular dysplasia [MVD])
• Disturbances in outflow
Acquired (APSSs)
• Multiple, extrahepatic shunts
• Secondary to hepatic fibrosis (cirrhosis)
• Secondary to hepatic arteriovenous malformations (HAVMs)

11. Metabolic Diseases of the Liver
• A metabolic hepatopathy could be defined as any insult to the liver due to accumulation of
products of normal or abnormal metabolic pathways.
• This encompasses primary and secondary conditions and there is an overlap between
these two. For example, a secondary, clinically insignificant accumulation of fat (steatosis)
due to primary familial hyperlipidaemia in a dog may be associated with development of
gallbladder mucocele and clinically significant biliary stasis
Vacuolar Hepatopathies, Steatosis, Hyperlipidemia and Feline Hepatic Lipidosis
• The most common predominantly secondary metabolic hepatopathies in small animals
are the vacuolar hepatopathies, where hepatocytes become loaded with fat (steatosis) or
glycogen or water (hepatocellular swelling, or cloudy swelling)
• Several lysosomal storage diseases in dogs and cats also lead to hepatocyte vacuolation.
Cloudy swelling occurs when hepatocytes are injured and less able to maintain fluid
homeostasis.

12. C a u s e s o f P r i m a r y a n d S e c o n d a r y Va c u o l a r
H e p a t o p a t h i e s in C a t s
Steroid Hepatopathy and Cloudy Change
• Steroid hepatopathy—secondary to high concentrations of circulating corticosteroids
(exogenous or endogenous)
• Deficiency or toxicosis.
• Secondary to hepatic insult from another disease process, e.g., congestive heart
failure, neoplasia, other
hepatobiliary disease, gastrointestinal disease, renal disease, infectious disease
Steatosis
• Feline hepatic lipidosis—primary or secondary{obesity, anorexia, and stress are
important predisposing factors }
• Toxicoses—for example, vitamin A intoxication (cats)
• Secondary to canine familial hyperlipidemia
• Secondary to endocrine disease: hypothyroidism and diabetes mellitus (dogs);
occasionally hyperthyroidism (cats)

13. Feline Hepatic Lipidosis
• FHL has been defined as “a diffuse involvement of >50% of hepatocytes with cytoplasmic
vacuoles consistent in appearance with lipid.”
• Cats have a propensity to develop mild to moderate hepatic steatosis when anorexic for
any reason and also in response to toxic hepatic insults. It is important to differentiate this
mild steatosis from true hepatic lipidosis. It is also important to differentiate lipidosis of
hepatocytes from Ito cell proliferation
• FHL is reported in two forms: primary idiopathic and secondary
• The primary form occurs in overweight cats that have been fasted for a prolonged period
of time but have no identified underlying disease.
• Secondary FHL is recognized in association with another disease, particularly cholangitis,
pancreatitis, inflammatory bowel disease, neoplasia, diabetes mellitus, or hyperthyroidism.
• In both primary and secondary disease, it is proposed that fasting combined with stress
increases peripheral lipolysis and that there is a bottleneck effect in the liver, such that the
mobilized lipids become trapped, with reduced export.
• Cats with FHL have elevated circulating triglycerides and non-esterified fatty acids, consistent
with lipolysis of peripheral fat and reduced function of hormone sensitive lipase.23 The
triglyceride content of a normal cat’s liver is 1% whereas it increases to 43% in a cat with FHL

14. • It has been suggested that concurrent protein deficiency and negative nitrogen balance
associated with fasting reduce the ability to produce apoproteins to export fat from the
liver and that taurine and carnitine deficiencies contribute to the pathogenesis,
although the experimental evidence for these effects is limited.
• The resultant marked steatosis of hepatocytes interferes with the metabolic activity of the
cells and produces a secondary cholestasis due to compression of small intrahepatic
cholangioles. Thus, the result is a form of acute (potentially reversible) liver failure, with
severe clinical signs and effects on hepatic function
• Clinical signs are typical of acute-onset hepatic insufficiency with vomiting, anorexia,
weakness, and weight loss.

15. Amyloidosis
Feline Hepatic Amyloidosis
The tissue tropism of SAA varies between dogs and cats and between individual animals and
breeds.
Hepatic amyloidosis, where the liver is the primary site of clinical importance, is described
most commonly in cats
Amyloidosis in cats is most commonly familial and systemic (associated with SAA), although
it can be sporadic. In Abyssinian cats, the disease usually presents as chronic kidney
disease, with the renal medulla involved more than the glomeruli
Cats with hepatic amyloidosis most commonly present because of acute intraabdominal bleeding
from the fracture of a very friable liver, causing anemia and hypotension that can be fatal.
Cats also can present with jaundice and hepatomegaly as primary findings. On physical
examination, hepatomegaly is common.

16. Toxic Hepatic Diseases
D r u g s a n d C h e m i c a l s C o m m o n l y A s s o c i a t e d w i t h D o s a g e -
D e p e n d e n t H e p a t o t o x i c o s i s i n D o g s ( D ) o r C a t s ( C )
Acetaminophen
Aflatoxin
Amanita mushrooms
Azole antifungals
Glipizide
Phenazopyridine

17. D r u g s M o s t A s s o c i a t e d w i t h I d i o s y n c r a t i c H e p a t o t o x i c o s i s i n D o g
s( D ) o r C a t s ( C )
Carprofen (D)
Diazepam (C)
Mitotane (D)
Methimazole (C)
Potentiated sulfonamides (D)
Zonisamide (D)

18. Diseases of the Gallbladder and Extrahepatic Biliary
System• Cholelithiasis and Choledocholithiasis
• Cholecystitis
• Emphysematous Cholecystitis
• Biliary Neoplasia
• Gallbladder Mucoceles

19. Liver Failure
Liver disease occurs when the liver is damaged, resulting in loss of function.
It can be acute (sudden onset) or chronic (slow and progressive).
The most common cause of liver failure in cats is idiopathic hepatic lipidosis.
The next most common cause is Cholangiohepatitis(cholangitis).
Hepatic Lipidosis is the most common type of liver disease in the cat and occurs when your
cat becomes anorexic (stops or reduces the amount of food he is eating), the body begins to
use fat stores as fuel. These fat stores are sent to the liver, to be broken down to supply
nutrients. Unfortunately, the liver sometimes becomes overwhelmed and is unable to
process this fat as quickly as necessary, leading to a build-up of fat in the liver,
which interferes with normal liver function
Other Causes of Liver Damage
Toxins
Portosystemic Shunt
Acute Hepatic Failure in Cats
Hepatic failure, or acute liver failure, is a condition characterized by the sudden loss of 70
percent or more of the liver’s function. This diseased state may be due to sudden, massive,
hepatic necrosis (tissue death in the liver).

20. Symptoms
Clinical signs may vary depending on what has caused the liver disease, and
symptoms can often be vague and non-specific.
Early symptoms you may notice include:
•Loss of appetite (anorexia) – One of the early signs of liver disease in cats
•Weight loss – Another early sign of liver disease
Signs of severe liver damage include:
•Diarrhoea
•Vomiting
•Lethargy
•Bad breath
•Jaundice (icterus)
•Ascites (abdominal effusion) – Build-up of fluid in the peritoneal cavity caused by portal
hypertension (high blood pressure) in the portal vein of the liver
•Polyuria (increased urination)/polydipsia (increased thirst)
•Hepatomegaly (enlargement of the liver) or micro-hepatica (small liver)
•Dark coloured but clear urine caused by the presence of bilirubin
•Seizures – A build-up of toxins due to the liver no longer functioning properly can lead
to seizures

21. Jaundice
Jaundice is defined as yellow discoloration of the sclera, skin and mucous membranes
due to deposition of the pigment bilirubin.
When bilirubin serum levels rise above 2.0 mg/dL in a dog or cat, one is typically able
to discern the yellow hue.
“Jaundice” is not a disease; rather, it is a clinical manifestation of an underlying disease
process. There is a multitude of disease processes that can ultimately result in jaundice.
Pathophysiology ? We all know
C a u s e s o f J a u n d i c e
Pre-hepatic (Hemolysis)
Immune-mediated hemolytic anemia
Infectious
• Mycoplasma spp., Babesia spp., Cytauxzoon felis
Heinz body anemia
• Toxins/drugs (acetaminophen, onions, zinc)
• Hepatic lipidosis
Hypophosphatemia
Genetic disorders
• Osmotic fragility syndrome, phosphofructokinase deficiency, pyruvate kinase deficiency

22. Hepatic
Infectious
• Viral (feline infectious peritonitis, canine adenovirus-1)
• Bacterial (Leptospira spp., Salmonella spp., rickettsial disease)
• Protozoal (Toxoplasma gondii, Neospora caninum)
• Fungal (histoplasmosis, coccidioidomycosis)
• Parasitic (Heterobilharzia americana, visceral larval migrans)
Inflammatory/immune-mediated disease
Toxins
• Amanita spp., aflatoxin, Sago palm, cyanobacteria
Drugs
• Carprofen, acetaminophen, azathioprine, methimazole
Neoplasia
Copper-associated hepatopathy
Lysosomal storage disease
Post-hepatic
Intraluminal bile duct obstruction
• Mucocele, cholelith, inflammation, stricture, neoplasia
Extraluminal bile duct obstruction
• Pancreatitis, neoplasia, lymphadenopathy, duodenal foreign body

23. Diagnostic Plan
The complete blood count (CBC) should help identify and characterize the anemia, if
present. Hemolysis typically causes a macrocytic, hypochromic, regenerative anemia while
chronic liver disease may cause a microcytic, normochromic nonregenerative anemia.
Microcytic hypochromic anemia is typically due to chronic blood loss, such as occurs
with severe flea infestation or GI bleeding.
Cats with hepatic lipidosis may develop a regenerative Heinz body anemia. Spherocytosis and
autoagglutination confirm immune-mediated destruction of erythrocytes, and an inflammatory
leukogram is often present.
Thrombocytopenia may be noted with IMHA or DIC, which can develop secondary to liver failure
or severe inflammatory states like pancreatitis or bile peritonitis.
The chemistry panel should include alkaline phosphatase (ALP), alanine aminotransferase
(ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), cholesterol,
blood urea nitrogen (BUN), albumin, glucose and bilirubin.
Abdominal imaging, with either radiographs or ultrasound, is valuable. Abdominal radiographs
may show a penny or other foreign body causing zinc toxicosis, mass lesions or choleliths.

24. Diagnostic Evaluation of the Liver
• The liver has a remarkable regeneration capacity after significant loss.
• However, liver diseases associated with fibrosis, inflammation or viral infections impair
this regenerative process and liver function deteriorates.
• Because the liver has such an incredible ability to regenerate, more specific signs of liver
disease such as icterus, ascites, bleeding tendencies, hypoglycemia, and hepatic
encephalopathy (HE) typically do not develop until the end stages of a disease process.
Early clinical signs of liver disease such as vomiting, diarrhea, lethargy, polyuria (PU),
polydipsia (PD), and inappetence are extremely nonspecific. Thus, diagnosing primary
hepatobiliary disease can be challenging.
• A logical approach encompassing patient signalment, history, physical exam findings,
biochemical and hematologic abnormalities, diagnostic imaging, and liver sampling
should be used to obtain a diagnosis.
Signalment and History
Breed Predispositions
For example, middle-aged, overconditioned cats with a recent history of weight loss and
anorexia should raise suspicion for feline hepatic lipidosis (FHL).
Hepatic amyloidosis has been documented in Abyssinian, Oriental, and Siamese cats
In cats, PSSs tend to be extrahepatic, and overrepresented breeds
include the Domestic Short Hair, Persian, Siamese, Himalayan, and Burmese.

25. Physical Examination
Icterus
The most sensitive places to look for icterus on physical examination are the sclera, third
eyelid, soft palate, and below the tongue . Usually, icterus cannot be detected until the serum
bilirubin concentration is greater than 3.0 mg/dL. On the other hand, visibly icteric plasma
(seen on microhematocrit tubes) or serum can be seen when the bilirubin concentration is
over 0.5-1.0 mg/dL.
Dermatologic Signs
Ulceration and crusting of oral mucocutaneous junctions and ulceration of the
pinnae, periocular areas, interdigital areas, ventral abdomen, and inguinal
areas with or without crust formation is seen in cats
Ascites
Ascites in liver disease is typically due to portal hypertension (PH), though decreased
vascular oncotic pressure from hypoalbuminemia may also play a role
Portal hypertension can also lead to the development of multiple acquired portosystemic
shunts (MAPSS) and hepatic encephalopathy
Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a dysfunction of the brain secondary to liver dysfunction

26. Laboratory Evaluation of Hepatobiliary Disease
Liver Enzymes
Elevated serum liver enzyme activities are often the first finding that prompts suspicion of the
presence of hepatobiliary disease. Liver enzymes evaluated on typical biochemical panels
include alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
phosphatase (ALP), and gamma-glutamyl transpeptidase (GGT).
These enzymes reflect hepatocyte membrane integrity (ALT and AST), hepatocyte or
biliary epithelial necrosis (ALT and AST), cholestasis (ALP and GGT), or an induction
phenomenon (ALP and GGT)
Liver Function Parameters and Liver Function Testing
Glucose
Blood Urea Nitrogen (BUN)
Albumin/Globulin
Cholesterol
Bilirubin
Bile Acids
Ammonia
Coagulation Proteins

27. Hematologic Findings
• The most consistent abnormalities found on a complete blood cell count (CBC)
include microcytosis (associated with impaired iron transport in patients with vascular
abnormalities), target cells, poikilocytosis and Heinz body formation (cats)
• Anemia may occur secondary to hemorrhage from gastrointestinal ulceration seen with
advanced liver disease, a bleeding disorder, or anemia of chronic disease
Urinalysis
• The majority of these are nonspecific. The one specific finding for liver disease on
a urinalysis is that of bilirubinuria in cats.
• Cats with hepatic lipidosis may have refractile fat globules in the urine (lipiduria) on urine
sediment examination
Imaging of the Liver
Radiography
Ultrasonography
Other Imaging Modalities
Computed Tomography (CT)
Magnetic Resonance Imaging (MRI)
Portal Scintigraphy Using 99MTc-Sulfur Colloid
Trans-Splenic Portal Scintigraphy (TSPS)
Sampling of the Liver
Fine-Needle Aspiration of the Liver
Hepatic Biopsy

28. Thank you