Cholangitis in cats: symptoms, cause, diagnosis, treatment, and prognosis

Inflammation of the bile ducts is common in cats. This review article reports on what is currently known about the various types of cholangitis (i.e., cholangitis caused by liver flukes, neutrophilic cholangitis, and lymphocytic cholangitis). Treatment is available for cholangitis caused by liver flukes and for neutrophilic cholangitis, and the prognosis is good. However, the cause of lymphocytic cholangitis is not known and there is currently no evidence-based therapy. Several causes are mentioned in the literature, but more research is needed in order to establish the cause of this disease and to develop an appropriate therapy.     

Statistical relevance of ultrasonographic criteria in the assessment of diffuse liver disease in dogs and cats

OBJECTIVE: To determine whether objectively applied ultrasonographic interpretive criteria are statistically useful in differentiating among 7 defined categories of diffuse liver disease in dogs and cats. SAMPLE POPULATION: Ultrasonographic images of 229 dogs and 104 cats. PROCEDURES: Liver parenchymal or related sonographic criteria established by the authors were retrospectively and independently applied by 3 radiologists who were not aware of patient status or patient laboratory data. Seven histologic or cytologic categories of diffuse (infiltrative but not nodular) liver diseases were jointly established by the authors and included normal liver; inflammation; round-cell neoplasia; non-round-cell infiltrative, prenodular (early) metastatic neoplasia; lipidosis; vacuolar hepatopathy; and other. Liver parenchymal sonographic criteria included parenchymal sound attenuation with increasing depth, comparative organ echogenicity (liver, spleen, and kidneys), diffuse or patchy hyperechoic or hypoechoic echotexture, uniform or coarse echotexture, portal venous clarity, and liver lobe geometry. Related extrahepatic criteria included gallbladder wall thickness, bile duct diameter, amount and character of gallbladder precipitate, nondependent shadowing in the gallbladder, hepatic vein diameter versus caudal vena cava diameter, peritoneal fluid, spleen echotexture (normal vs abnormal [characterized]), and kidney echotexture. Ultrasonographic criteria were statistically compared to the 7 categories of diffuse liver disease in search of clinically exploitable relationships. RESULTS: Statistical evaluation of the applied ultrasonographic criteria did not yield clinically acceptable accuracy for discrimination among the 7 categories of diffuse liver diseases (including normal liver) in either species. CONCLUSIONS AND CLINICAL RELEVANCE: Criterion-based ultrasonographic appearance was insufficient to discriminate among canine and feline diffuse infiltrative liver diseases.     

Suppurative cholangitis in cats

Suppurative cholangitis in 5 aged cats was characterized clinically by weight loss, depression, dehydration, icterus, and fever. The major abnormal laboratory findings were a severe left shift of WBC and a high, conjugated bilirubin concentration consistent with an inflammatory process and cholestasis. Gross pathologic findings included periductal biliary fibrosis (4 cats), periductal pancreatic fibrosis (2 cats), cholelithiasis (2 cats), deformation of the gallbladder (2 cats), and chronic interstitial pancreatitis (2 cats). Histopathologic findings in all cases were portal hepatic fibrosis, biliary hyperplasia, and suppurative exudate within dilated intrahepatic biliary ducts. Weight loss and portal fibrosis were suggestive of chronic, intermittent illness. The pathogenesis appeared to involve invasion of the bile duct by enteric bacteria. Cholangitis was observed to occur in association with pancreatitis, cholelithiasis, or anatomic abnormalities of the biliary tract.     

Correlation of cytologic and histopathologic findings with perinodal echogenicity of abdominal lymph nodes in dogs and cats

Abdominal lymphadenopathy in dogs and cats is routinely investigated with ultrasound. As the determination between benign and neoplastic etiologies of lymphadenopathy affects patient management, specific sonographic characteristics associated with both benign and neoplastic lymph nodes have been suggested. However, a significant overlap between these characteristics exists, necessitating a cytologic or histopathologic diagnosis in most instances. The objectives of this retrospective, cross‐sectional study were to evaluate whether echogenicity of perinodal fat could be a discriminator between benign and neoplastic abdominal lymphadenopathy and to assess if additional sonographic features associated with malignancy could be identified in lymph nodes with hyperechoic perinodal fat. Small animal patients (257 dogs and 117 cats) with sonographic evidence of abdominal lymphadenopathy and a cytological or histopathological diagnosis were evaluated for differences in the proportions of sonographic features between benign and neoplastic groups. Greater maximum long axis diameter (in dogs and cats) and a greater number of abnormal lymph nodes (in cats) were associated with malignancy in lymph nodes with hyperechoic perinodal fat. Canine lymph nodes with round cell neoplasia were significantly more likely to have hyperechoic perinodal fat. Lymph nodes affected with other neoplasia or with lymphadenitis were equally likely to have normal or hyperechoic perinodal fat. Reactive lymph nodes were significantly less likely to have hyperechoic perinodal fat in both species. These results suggest that though echogenicity of perinodal fat is a nonspecific finding, abdominal lymph nodes with hyperechoic perinodal fat are less likely to be reactive and sampling of these lymph nodes may be indicated.     

Sclerosing cholangitis in baboons (Papio spp) resembling primary sclerosing cholangitis of humans

Primary sclerosing cholangitis is a chronic and progressive cholestatic liver disease that has been extensively documented in the human literature. Although it shares many features in common with chronic lymphocytic cholangitis in cats, primary sclerosing cholangitis has never been reported in a nonhuman primate. Primary sclerosing cholangitis is characterized by the presence of intrahepatic and/or extrahepatic inflammation and concentric fibrosis of bile ducts, eventually leading to cirrhosis and hepatic failure. The pathogenesis and cause remain unknown, but the disease likely involves a multifactorial mechanism with genetic- and immune-mediated components. The authors report 2 cases that histologically resemble the condition in humans; they consist of 2 adult male baboons with a clinical history of chronic elevated liver enzymes. In both cases, the liver was histologically characterized by thick bands of fibrosis and mild lymphoplasmacytic periportal cholangiohepatitis with concentric periductal fibrosis, resulting in atrophy and loss of bile ducts. Immunohistochemical analysis revealed positivity of hepatocytes to cytokeratin 7. Masson stain demonstrated marked biliary fibrosis. This is the first report that resembles sclerosing cholangitis in a nonhuman primate, and it suggests that the baboon may provide a useful animal model for this condition in humans.     

Progressive lymphocytic cholangitis in the cat

A distinct type of liver disease is described in 21 cats. It is characterized morphologically by monolobular fibrosis, lymphocytic infiltrates which surround and permeate bile ducts and proliferation of bile ductules of varying intensity. The most common clinical signs are ascites, jaundice and hypergammaglobulinaemia. The condition appears to progress through an active stage of intense lymphocytic infiltration and proliferation of bile ductules to a stage of progressive monolobular fibrosis which results in distortion of liver architecture. The rate of progression is very variable. The condition differs from that of ascending or suppurative cholangitis described in the cat and bears only superficial resemblances to various forms of cholangitis in man and other species. At present the aetiology is unknown but it is suggested that genetic and immunological factors may predispose certain animals to produce hepatic lesions after exposure to a variety of environmental factors.     

THE SONOGRAPHIC APPEARANCE OF INTESTINAL MUCOSAL FIBROSIS IN CATS

The medical records of 11 cats with full‐thickness intestinal biopsies and histopathologic confirmation of segmental mucosal fibrosis were reviewed. All cats received an abdominal ultrasonographic evaluation. The sonographic feature of a small intestinal mucosal hyperechoic band paralleling the submucosa was present in all cats. Other intestinal sonographic findings included wall thickening, and altered wall layering (increased mucosal echogenicity, thickened submucosa, and/or muscularis layer). None of the cats had complete loss of wall stratification. All cats had clinical signs related to the gastrointestinal (GI) tract at the time of presentation. Three of the 11 cats had palpably thickened small intestinal loops, 3/11 abdominal pain, and 2/11 abdominal fluid. Histopathologically, mucosal fibrosis was associated with inflammatory cell infiltrates in all cats. In those cats with histopathologic evidence of mural fibrosis, all cats had a visible hyperechoic band through several intestinal segments. We speculate that the hyperechoic mucosal band represents the zone of mucosal fibrosis. Independently and prospectively, we reviewed the clinical presentation of 35 cats having this visible hyperechoic mucosal band on ultrasound. Twenty‐four of these 35 cats had clinical signs related to the digestive system at the time of record. Our study suggests that the hyperechoic mucosal band represents fibrosis, and in presence of concurrent GI signs, further diagnostic tests may be warranted.     

Choledochal cyst with secondary cholangitis,choledochitis, duodenal papillitis,and pancreatitis in a young domestic shorthair cat

Choledochal cysts, congenital segmental dilations of the common bile duct, have been reported in few cats, and histologic characterization is lacking. A 20-mo-old spayed female domestic shorthair cat was presented because of vomiting and weight loss. There was progressive elevation of liver enzyme activity (ALT > ALP, GGT) and hyperbilirubinemia. Diagnostic imaging identified focal cystic dilation of the common bile duct, dilation and tortuosity of adjacent hepatic ducts, and a prominent duodenal papilla. A choledochal cyst was suspected, and the animal was euthanized. On postmortem examination, there was a 2-cm, firm, thickened, cystic dilation of the common bile duct, patent with adjacent ducts. Histologically, the cyst wall was expanded by fibroblasts, collagen, and lymphoplasmacytic inflammation. Adjacent bile ducts were markedly dilated and tortuous, with lymphoplasmacytic inflammation and papillary mucosal hyperplasia that extended to the major duodenal papilla. There was chronic neutrophilic cholangitis, suggesting bacterial infection and/or disturbed bile drainage, extrahepatic obstruction, and lymphoplasmacytic pancreatitis with ductular metaplasia. Prominent lymphoid follicles within biliary ducts and duodenum suggested chronic antigenic stimulation. Choledochal cysts can be associated with chronic neutrophilic cholangitis, extrahepatic obstruction, choledochitis, duodenal papillitis, and pancreatitis, and should be a differential for increased hepatic enzymes and hyperbilirubinemia in young cats.     

ULTRASONOGRAPHIC EVALUATION OF BILIARY CYSTADENOMAS IN CATS

The purpose of this study was to describe the ultrasonographic appearance of biliary cystadenomas in cats and compare the findings to a similar rare form of liver tumor in humans. Biliary cystadenomas are uncommon, benign liver tumors of older cats that may occur as focal or multifocal cystic lesions within the liver. The records of 10 cats which had abdominal ultrasonography and histologic diagnosis of biliary cystadenoma were reviewed. The average age of affected cats was 13.3 years (range 10-16 years). Eight cats were neutered males and two were neutered females. In three cats, the tumors were not seen ultrasonographically due to their small size or from being obscured by near-field reverberation echoes. The remaining seven cats had solitary (4 cats) or multifocal (3 cats) masses corresponding to variable ultrasonographic patterns: multilocular masses containing thin-walled cysts, hyperechoic masses with cystic components, or masses of mixed echogenicity with cystic components. The masses had variable ultrasonographic patterns when multifocal disease was present. Recognizable cysts were evident somewhere within the tumors seen ultrasonographically, although sometimes the cysts appeared very small. The biliary cystadenomas were thought to be clinically silent. Although liver enlargement or a cranial abdominal mass was palpable in 4 cats, no consistent trend of clinical signs, CBC or serum biochemical abnormalities could be directly attributed to biliary cystadenoma. The treatment of choice is surgical resection of the tumor, as continued growth may compress adjacent vital structures within the liver. The differential diagnosis of biliary cystadenomas from other cystic liver lesions such as hepatic cysts, hematomas, abscesses, parasitic cysts, or other liver tumors is discussed.     

Cholangitis and Cholangiohepatitis in Dogs: A Descriptive Study of 54 Cases Based on Histopathologic Diagnosis (2004–2014)

Background

Cholangitis in dogs appears to be more common than previously thought, but understanding of the disease remains incomplete.

Objective

To describe a population of dogs with cholangitis or cholangiohepatitis.

Animals

Fifty‐four client‐owned dogs with cholangitis or cholangiohepatitis.

Methods

Medical records of dogs with cholangitis or cholangiohepatitis confirmed by histopathology between January 2004 and December 2014 were identified using a computer‐based search and retrospectively reviewed.

Results

Clinical signs included vomiting (72.2%), lethargy (70.4%), and inappetence (64.8%). Most dogs (49/50) had increased liver enzyme activities, hyperbilirubinemia (32/50), and hypercholesterolemia (24/43). Ultrasonographic abnormalities of the hepatobiliary system were seen in 84% of cases. On histopathology, 53 of 54 affected dogs had neutrophilic cholangitis (NC) or cholangiohepatitis, whereas 1 dog had lymphocytic cholangitis. Most cases (42/54) were chronic. Evidence of concurrent biliary disease (46.2%) and biliary tract obstruction (42.6%) was common. Seventeen of 36 biliary and 11 of 25 liver cultures were positive for bacterial growth; Escherichia coli and Enterococcus spp. were most common. Median patient survival was 671 days (95% confidence interval [CI]: 114–1,426). On Cox regression, dogs that did not have a cholecystectomy performed had a 2.1 greater hazard for death (P = 0.037; 95% CI: 1.0–4.3) compared to cholecystectomized dogs. Dogs >13 years old had a 5.0 greater hazard for death (P = 0.001; 95% CI: 1.9–13.2) compared to younger dogs.

Conclusions and Clinical Significance

Chronic NC or cholangiohepatitis was most common. Cholecystitis and biliary tract obstruction often occurred in conjunction with cholangitis. Cholecystectomized dogs had decreased risk of death; thus, cholecystectomy may improve patient outcome.     

QUALITATIVE ULTRASONOGRAPHY OF THE LIVER IN OBESE CATS

A prospective study was undertaken to compare the relative echogenicity of the liver and the fat of the falciform ligament in two groups of clinically normal obese cats. In the first group of cats, four of eight normal weight cats were fed a high calorie diet ad libitum for a 12 week period at which time they were considered obese. The liver was hyperechoic when compared to the adjacent fat of the falciform ligament in the obese cats. In the second group of cats, the body condition of a group of eight clinically normal cats was subjectively graded. On ultrasonographic examination, the liver of those cats considered to be overweight were hyperechoic compared to the adjacent fat of the falciform ligament. Results from this study suggest that clinically normal obese cats may have a liver that is hyperechoic relative to the fat of the falciform ligament.     

ULTRASONOGRAPHIC EVALUATION OF GALLBLADDER WALL THICKNESS IN CATS

Ultrasonography of the gallbladder and biliary tract was performed on 42 cats: 22 clinically healthy cats (group A) and 20 cats with hepatobiliary disease and post mortem confirmation of gallbladder abnormalities (group B). The gallbladder wall was visible in 9 of 22 cats in group A and all 20 cats in group B. Additional gallbladder findings in group B included shape anomalies, biliary tract obstruction, wall thickening, polyps, neoplasia, and biliary sludge. Ultrasonographic evaluation of abdominal organs identified pancreatic disease as the predominant pathological cause of extrahepatic biliary obstruction. Hepatic parenchymal involvement was noted with inflammation and thickening of the gallbladder wall. Histologically, gallbladder walls were characterized by mucous gland hyperplasia, inflammation, infiltration, edema, epithelial detachment, and/or neoplasia. Ultrasonographic and histologic gallbladder wall measurements of 20 cats in group B agreed within 0.4 mm and all cats with a gallbladder wall thickness > or =1.0 mm had histopathologic abnormalities of the wall. Serum biochemical analysis revealed elevations of one or more parameters in all cats of group B, but was non-specific for a gallbladder lesion. The results of this study indicate that a visible, echogenic gallbladder wall can be considered a normal variant and is not always associated with hepatobiliary disease. Ultrasonography is accurate in measuring gallbladder wall thickness. Wall thickness greater than 1 mm is accurate in predicting gallbladder disease in cats, while a thickness less than 1 mm cannot rule out mild or chronic inflammation.     

Hepatobiliary Scintigraphy in the Evaluation of Feline Liver Disease

Hepatobiliary scintigraphy (HBS) was performed in 10 cats with histologically documented hepatobiliary disease. The scintigraphic patterns were classified into one of 5 categories: normal, primary hepatocellular dysfunction, primary in-trahepatic cholestasis, mixed hepatocellular and intrahe-patic cholestasis, and extrahepatic obstructive patterns. Initial attempts were made to correlate specific disease entities with HBS patterns, but a consistent relationship could not be determined. A correlation between the histological severity of a given hepatic disease and the HBS pattern was made. All cats (n = 5) with a mixed hepatocellular and intra-hepatic cholestasis scintigraphic pattern with normal gallbladder function had a histologically severe form of their individual hepatic disease. Three of the 4 cats with an intra-hepatic cholestasis pattern and normal hepatocellular and gallbladder function had histologically mild or moderate forms of their individual hepatic disease. One cat had an extrahepatic obstructive pattern where no radiopharmaceu-tical was identified in the gallbladder or small intestine by 3 hours postinjection. This study suggests that HBS can be useful in cats with hepatobiliary disease to assess the severity of hepatic dysfunction, and to determine if extrahepatic biliary obstruction is present. Correlation between HBS patterns and specific disease entities such as hepatic lipidosis or cholangitis-cholangiohepatitis syndrome could not be made in this study.     

ULTRASONOGRAPHIC ASSESSMENT OF SINCALIDE-INDUCED CANINE GALLBLADDER EMPTYING: AN AID TO THE DIAGNOSIS OF BILIARY OBSTRUCTION WINNER OF THE 1991 RESIDENT-AUTHORED PAPER AWARD SPONSORED BY THE AMERICAN COLLEGE OF VETERINARY RADIOLOGY

Gallbladder emptying studies using ultrasonography were performed on ten normal dogs, one normal control dog, three dogs with biliary obstruction and three dogs with nonobstructive hepatobiliary disease. An intravenous bolus of a synthetic cholecystokinin was used to induce emptying. The normal canine gallbladder emptied at least 40% of its volume within one hour of synthetic cholecystokinin (0.04 μg/kg) administration. Maximum response was seen within 5 to 20 minutes. The gallbladder in icteric dogs with nonobstructive hepatobiliary disease (1 cholecystitis, 1 cholangitis, 1 cholangiohepatitis) also emptied at least 40% of its volume within one hour. The obstructed gallbladder (1 chronic pancreatitis, 1 acute pancreatitis, 1 pancreatic mass) emptied less than 20% within one hour. A significant difference (p>0.05) in the maximum percent gallbladder emptying was found between the dogs with biliary obstruction and nonobstructed, icteric dogs. No side effects to the synthetic cholecystokinin were observed.     

EFFECT OF SEVOFLURANE ANESTHESIA AND BLOOD DONATION ON THE SONOGRAPHIC APPEARANCE OF THE SPLEEN IN 60 HEALTHY CATS

The aims of this prospective study were to describe the normal sonographic size and appearance of the feline spleen, and to test effects of sevoflurane anesthesia and blood collection on sonographic characteristics. Sonographic evaluations were performed in 60 healthy blood donor cats prior to anesthesia and blood collection (baseline), after anesthesia induction, after completion of blood collection while under anesthesia, and 7–10 days after blood collection. Transverse sonographic images of the splenic mid‐body were made. Splenic height, width, cross‐sectional area, echogenicity relative to the left renal cortex, and echotexture were recorded. Height, width, and cross‐sectional area were compared across time periods using linear‐mixed effects models. Holm's method was applied to adjust for multiplicity and control the overall Type 1 error rate at α = 0.05. Normal transverse sonographic splenic measurements (mean ± standard deviation) at baseline were: height 8.2 ± 1.4 mm; width 26.7 ± 4.4 mm; and CSA 1.6 ± 0.5 cm². While there were statistically significant differences in splenic height, width, and cross‐sectional area after sevoflurane anesthesia and/or blood collection, differences were of low magnitude. The spleen was diffusely homogenous and subjectively isoechoic or mildly hyperechoic relative to the left renal cortex. In 77% of castrated male cats, the spleen was isoechoic to the left renal cortex. We conclude that sevoflurane anesthesia and blood donation do not subjectively alter splenic dimensions, echogenicity and echotexture in normal cats.     

Association of Helicobacter with cholangiohepatitis in cats

Infection with Helicobacter spp. is increasingly linked with hepatobiliary inflammation and neoplasia in people and in a variety of animals. We sought to determine if Helicobacter species infection is associated with cholangiohepatitis in cats. Deoxyribonucleic acid was extracted from tissue blocks from cats with cholangiohepatitis (32), noninflammatory liver disease (13), and cats with normal liver histology (4). Deoxyribonucleic acid was polymerase chain reaction-amplified with 2 sets of Helicobacter genus-specific primers, gel purified, and sequenced. Polymerase chain reaction-positive hepatic tissue was further examined with Steiner's stain, immunocytochemistry for Helicobacter species, and eubacterial fluorescent in situ hybridization. Gastric tissues of cats with known Helicobacter infection status served as controls for deoxyribonucleic acid extraction and sequence comparison. Helicobacter species were detected in 2/32 cats with cholangiohepatitis, and 1/17 controls. Sequences had 100% identity with Helicobacter species liver, Helicobacter pylori, and Helicobacter fenelliae/cinaedii in a cat with suppurative cholangitis, Helicobacter species liver, Helicobacter pylori, and Helicobacter nemistrineae in a cat with mild lymphocytic portal hepatitis, and Helicobacter bilis in a cat with portosystemic vascular anomaly. In contrast, sequences from gastric biopsies showed highest homology (99-100%) to "Helicobacter heilmannii," Helicobacter bizzozeronii, Helicobacter felis, and Helicobacter salomonis. Fluorescent in situ hybridization revealed a semicurved bacterium, with Helicobacter-like morphology, in an intrahepatic bile duct of the cat with suppurative cholangitis. This study has identified Helicobacter deoxyribonucleic acid in 2/32 cats with cholangiohepatitis and 1/13 cats with noninflammatory liver disease. Deoxyribonucleic acid sequences of hepatic Helicobacter species were distinct from those found in the stomach and are broadly consistent with those identified in cat intestine and bile, and hepatobiliary disease in people and rodents.     

Gallbladder perforation associated with cholelithiasis and cholecystitis in a dog

A four-year-old female Japanese akita was admitted with icterus, ascites and chronically elevated serum bilirubin and liver enzymes. Abdominal ultrasonography revealed a diffusely thickened, hyperechoic gallbladder wall with a focal defect, hepatic lymphadenopathy and a large volume of anechoic fluid within the peritoneal space. Diagnosis of biliary tract rupture with bile peritonitis was based on the findings of bile and suppurative exudate in peritoneal aspirates. A perforated gallbladder and cholelithiasis were found on exploratory celiotomy, while histopathology revealed chronic suppurative cholecystitis. The dog recovered uneventfully after cholecystectomy. Although rare, the triad of cholelithiasis, cholecystitis and gallbladder perforation should be considered after detection of one of these conditions.     

Alkaline phosphatase, leucine aminopeptidase, and alanine aminotransferase activities with obstructive and toxic hepatic disease in cats

The activities of serum alkaline phosphatase (serum ALP), leucine aminopeptidase (serum LAP), and alanine aminotransferase (serum ALT) were determined in 15 cats before and after treatment by 3 methods: common bile duct occlusion, left hepatic duct(s) occlusion, and carbon tetrachloride administration. Significant increases in serum ALP, LAP, and ALT activities occurred in all cats in the 3 groups. Sustained mean increases of ninefold in ALP and 13-fold in LAP occurred in the cats with common bile duct occlusion. Lesser mean increases of these enzymes (fourfold) occurred in the cats with partial biliary occlusion. Transient mean increases (100-fold) in ALT occurred in the carbon tetrachloride-treated cats. Urine ALP excretion was measured in 3 cats with common bile duct occlusion. There was no significant difference between rates of urine ALP excretion before and after common bile duct occlusion. Specific ALP activities of hepatic extracts from normal cats and biliary-obstructed cats were compared. Mean specific activity was onefold higher in liver from cats with common bile duct occlusion of 21 days' duration. The findings in the present studies were interpreted to indicate that serum ALP and LAP are useful to detect biliary occlusive disease in cats and, in conjunction with serum ALT, may be used to differentiate primary hepatodegenerative disease and biliary occlusive disease.     

Temporary Bile Diversion in Cats with Experimental Extrahepatic Bile Duct Obstruction

The use of a cholecystostomy catheter for temporary bile diversion was investigated in four cats with experimentally induced extrahepatic bile duct obstruction. Eighteen days after ligation of the common bile duct, a 6.5 F accordion catheter was placed in the gallbladder with a 22 g Hawkins needle-guide system through a paracostal incision. Biochemical parameters and fasting serum bile acids were monitored for 16 days. There were significant decreases in mean total bilirubin, aspartate aminotransferase, and fasting serum bile acids within 72 hours of bile diversion, and in mean alanine aminotransferase within 96 hours. Attitude and appetite improved, and the catheter was tolerated well. Positive bile cultures developed in three cats. Histologic changes in the gallbladder included mucosal ulcerations, a mixed inflammatory cellular infiltration, and fibrosis of the submucosa.