Concurrent hepatopathy in dogs with gallbladder mucocele: Prevalence, predictors, and impact on long-term outcome.

BACKGROUND: Information is limited regarding the prevalence and importance of hepatic histologic abnormalities in dogs with gallbladder mucocele (GBM). OBJECTIVES: To (a) report prevalence of hepatic histologic abnormalities in dogs with GBM (b) evaluate for association between hepatic abnormalities and outcome in dogs with GBM (c) evaluate whether neutrophil-to-lymphocyte ratio (NLR) differs in dogs with GBM with and without specific hepatic lesions. ANIMALS: Fifty-two dogs with grossly and histologically confirmed GBM. METHODS: Multicenter, retrospective study of dogs with GBM undergoing cholecystectomy with concurrent liver biopsy. Archived histological sections of gallbladder and liver evaluated by investigators blinded to data. Proportions of dogs with each histologic abnormality alive vs deceased at 1, 3, and 12 months post-cholecystectomy compared. Mann-Whitney U performed to determine if NLR differed in dogs with or without selected lesions. RESULTS: 51/52 (98%, 95% CI [89%, 99%]) dogs with GBM had at least 1 hepatic histologic abnormality. Hepatic fibrosis (37/51; 73%, 95% CI [59%, 83%]), biliary hyperplasia (29/52; 56%, 95% CI [42%, 68%]), and portal inflammation (25/52; 48%, 95% CI [35%, 61%]) were most common. The proportion of dogs alive vs dead differed based on the fibrosis score at 1, 3, and 12 (P ≤ .04) months post-cholecystectomy. Dogs with hepatic necrosis (P = .006) and cholangitis/cholangiohepatitis (P = .02) had higher NLRs compared to dogs without these lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: Histologic abnormalities of the liver are common in dogs with GBM. A higher portal fibrosis score might be associated with shortened long-term survival after cholecystectomy for dogs with GBM. An increase in NLR might predict hepatic necrosis and cholangitis/cholangiohepatitis in dogs with GBM.

A multicenter retrospective study assessing progression of biliary sludge in dogs using ultrasonography.

BACKGROUND: Biliary sludge (BS) frequently is identified on ultrasonographic examination and is described as incidental. It is hypothesized that biliary stasis and hypersecretion play a role in both BS and gallbladder mucocele (GBM) formation. Recent studies have documented similarities in composition of BS and GBM, and there are several examples of progression from BS to GBM in the veterinary literature. OBJECTIVES: To assess the relationship between the presence of BS and later development of GBM in dogs, over time periods >12 months. ANIMALS: A total of 154 dogs with BS and ultrasonographic follow-up >12 months. METHODS: Medical records were retrospectively collected from 9 UK-based referral centers for all available time points. A semiobjective scoring system was used to track volume of BS within the gall bladder (GB) over time. RESULTS: Twenty dogs developed GBM during the study period. Shetland Sheepdogs (odds ratio [OR], 40.99; 95% confidence interval [CI], 3.61-465.95; P = .003) and Border Terriers (OR, 11.66; 95% CI, 3.28-46.63; P < .001) were independent risk factors for the development of GBM. Non-gravity-dependent BS (NDBS) was noted to form before GBM development in 9/20 dogs, and breeds at-risk for GBM were more likely to have NDBS. Odds for the development of GBM increased with BS score. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with NDBS may be at risk for the development of GBM and a stratified BS scoring system could allow for semiobjective monitoring over time, particularly in at-risk breeds.

Long-term survival of dogs treated for gallbladder mucocele by cholecystectomy, medical management, or both.

BACKGROUND: Gallbladder mucoceles (GBM) typically are treated by cholecystectomy. Medical management rarely has been reported and medical and surgical management have not been compared. HYPOTHESIS/OBJECTIVES: To compare survival of dogs treated for GBM by medical management or cholecystectomy or both. ANIMALS: Eighty-nine client-owned dogs diagnosed with GBM that received cholecystectomy or medical treatment or both from 2011 to 2017. METHODS: Potential cases were identified by searching the medical records database. Data collected included signalment, clinicopathologic results, treatments, and ultrasonographic images and reports. Dogs were grouped according to the treatment received (medical management, surgical treatment, or both) that was chosen at the discretion of the attending veterinarian. Survival analysis was performed and prognostic variables identified and compared between treatment groups. RESULTS: Of dogs surviving at least 14 days after diagnosis, median survival times were 1802 (95% confidence interval [CI], 855-not reached) days, 1340 (95% CI, 444-1340) days, and 203 (95% CI, 18-525) days, for the surgical, medical, and medical then surgical treatment groups, respectively, and differed significantly (P < .0001). Gallbladder mucocele type (P = .05), serum alkaline phosphatase activity (P = .0001), and serum creatinine (P = .002) and phosphorus (P = .04) concentrations were associated with decreased survival across groups. Suspicion of biliary rupture on abdominal ultrasound (AUS) examination was correlated with increased survival in the surgical group (P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Cholecystectomy for the treatment of GBM results in the best long-term survival in dogs surviving the immediate postoperative period (14 days) compared to medical management. Although medical management is associated with shorter survival compared to surgical treatment, it is a reasonable alternative when surgery cannot be pursued.

Reference limits for hepatic bile duct-to-arteriole and bile duct-to-portal tract ratios in healthy cats.

OBJECTIVE To establish reference limits for hepatic bile duct-to-arteriole ratio (BD:A) and bile duct-to-portal tract ratio (BD:PT) in healthy cats and assess whether these parameters could be used to support a diagnosis of biliary ductopenia in cats. SAMPLE Hepatic biopsy samples from healthy cats (n = 20) and cats with ductopenia (2). PROCEDURES Hepatic biopsy samples from healthy cats were used to count the number of bile ducts and hepatic arterioles in 20 portal tracts for each cat. Mean BD:A and mean BD:PT for each cat were calculated, and these values were used to determine reference limits for mean BD:A and mean BD:PT. Results of histologic evaluation, including immunohistochemical staining in some instances, were compared for healthy cats versus cats with ductopenia. RESULTS Of the 400 portal tracts from healthy cats, 382 (95.5%) and 396 (99.0%) had BD:A and BD:PT, respectively, ≥ 1.0, with less variability in BD:A. Mean BD:A and BD:PT were markedly lower in both cats with ductopenia, compared with values for healthy cats. However, only mean BD:A for cats with ductopenia was below the reference limit of 0.59. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that systematic evaluation of BD:A, with a lower reference limit of 0.59 to define biliary ductopenia in cats, may be a discrete and easily applied morphometric tool to enhance detection of ductopenia in cats. However, application of this ratio required evaluation of ≥ 20 portal tracts with cross-sectioned portal elements to determine a mean BD:A value.

Hepatobiliary diseases in buffalo (Bubalus bubalis): clinical, laboratory, and ultrasonographic findings.

This study describes ultrasonographic observations of five hepatobiliary diseases in buffalo (Bubalus bubalis). Fifty buffalo, including 20 clinically normal and 30 hepatobiliary diseased buffalo were enrolled in the study. Complete clinical, radiographic and ultrasonographic examinations and laboratory analyses were conducted. Focal parenchymal lesions including liver abscess (n = 12) and hepatic cyst (n = 6), diffuse parenchymal lesion (hepatobiliary cirrhosis, n = 5) and obstruction of hepatobiliary passages including cholestasis (n = 4), and hepatocholelithiasis (n = 3) were successfully imaged by ultrasonography. Hepatic abscess imaged as a hypoechoic to echogenic circumscribed mass of various diameters with a distinct echogenic capsule. Hepatic cyst imaged as a pear-shaped sac with a bright echogenic margin, anechoic content, and distal acoustic enhancement. In hepatobiliary fibrosis, the liver showed linear bands of increasing echogenicity with less distinct imaging of the portal vasculature. Cholestasis was imaged as dilatation of the gallbladder (GB) with wall thickening and homogeneous or heterogeneous contents. Hepatocholelithiasis imaged as an echoic structure within the hepatic parenchyma, or within and around the GB and bile duct, with more echogenicity of the hepatic parenchyma than normal. Ultrasonography can be an efficient rapid, noninvasive tool for screening of common hepatobiliary diseases in buffalo under field conditions.

Retrospective analysis of canine gallbladder contents in biliary sludge and gallbladder mucoceles.

The pathophysiology of canine gallbladder diseases, including biliary sludge, gallbladder mucoceles and gallstones, is poorly understood. This study aimed to evaluate the component of gallbladder contents and bacterial infection of the gallbladder in order to elucidate the pathophysiology of biliary sludge and gallbladder mucoceles. A total of 43 samples of canine gallbladder contents (biliary sludge, 21 and gallbladder mucoceles, 22) were subjected to component analysis by infrared spectroscopy, and the resultant infrared spectra were compared with that of swine mucin. Of the 43 samples, 41 were also evaluated by aerobic and anaerobic bacterial culture. The contents of 20 (95.2%) biliary sludge and 22 (100%) gallbladder mucocele samples exhibited similar infrared spectra as swine mucin. Although biliary sludge and gallbladder mucocele contents exhibited similar infrared spectra, one sample of biliary sludge (4.8%) was determined to be composed of proteins. The rate of bacterial infection of the gallbladder was 10.0% for biliary sludge and 14.3% for gallbladder mucoceles. Almost all of the identified bacterial species were intestinal flora. These results indicate that the principal components of gallbladder contents in both gallbladder mucoceles and biliary sludge are mucins and that both pathophysiologies exhibit low rates of bacterial infection of the gallbladder. Therefore, it is possible that gallbladder mucoceles and biliary sludge have the same pathophysiology, and, rather than being independent diseases, they could possibly represent a continuous disease. Thus, biliary sludge could be considered as the stage preceding the appearance of gallbladder mucoceles.

Use of Serum MicroRNAs as Biomarker for Hepatobiliary Diseases in Dogs.

BACKGROUND: Current biochemical indicators cannot discriminate between parenchymal, biliary, vascular, and neoplastic hepatobiliary diseases. MicroRNAs are promising new biomarkers for hepatobiliary disease in humans and dogs. OBJECTIVE: To measure serum concentrations of an established group of microRNAs in dogs and to investigate their concentrations in various types of hepatobiliary diseases. ANIMALS: Forty-six client-owned dogs with an established diagnosis of hepatobiliary disease and stored serum samples and eleven client-owned healthy control Labrador Retrievers. METHODS: Retrospective study. Medical records of dogs with parenchymal, biliary, vascular, or neoplastic hepatobiliary diseases and control dogs were reviewed. Concentrations of miR-21, miR-122, miR-126, miR-148a, miR-200c, and miR-222 were quantified in serum by real-time polymerase chain reaction. RESULTS: No different microRNA concentrations were found in the adenoma and congenital portosystemic shunt groups. In all other diseases, miR-122 concentrations were elevated with the highest concentration in the mucocele group (267-fold, CI: 40-1,768, P < .001). In dogs with biliary diseases, miR-21 and miR-222 were only increased in dogs with mucoceles (26-fold, CI: 5-141, P = .005 and 13-fold, CI: 2-70, P = .025, respectively). Uniquely increased microRNAs were found in the hepatocellular carcinoma group (miR-200c, 35-fold increase, CI: 3-382, P = .035) and the chronic hepatitis group (miR-126, 22-fold increase, CI: 5-91, P = .002). CONCLUSIONS AND CLINICAL IMPORTANCE: A microRNA panel consisting of miR-21, miR-122, miR-126, miR-200c, and miR-222 can distinguish between parenchymal, biliary, and neoplastic hepatobiliary diseases. Serum microRNA profiling is a promising new tool that might be a valuable addition to conventional diagnostics to help diagnose various hepatobiliary diseases in dogs.

Arterial blood gas anomaly in canine hepatobiliary disease.

Arterial blood gas analysis is an important diagnostic and monitoring tool for respiratory abnormalities. In human medicine, lung complications often occur as a result of liver disease. Although pulmonary complications of liver disease have not been reported in dogs, we have frequently encountered hypoxemia in dogs with liver disorders, especially extrahepatic biliary obstruction. In addition, respiratory disorders account for 20% of perioperative fatalities in dogs. Therefore, in this study, we evaluated the respiratory status in dogs with hepatobiliary disease by arterial blood gas analysis. PaO2 and PaCO2 were measured. Alveolar-arterial oxygen difference (AaDO2), the indicator of gas exchange efficiency, was calculated. Compared to healthy dogs (control group), hepatobiliary disease dogs had significantly lower PaO2 and higher AaDO2. Hypoxemia (PaO2 of ≤80 mmHg) was observed in 28/71 dogs with hepatobiliary disease. AaDO2 was higher (≥30 mmHg) than the control group range (11.6 to 26.4 mmHg) in 32/71 hepatobiliary disease dogs. By classifying type of hepatobiliary disease, dogs with extrahepatic biliary obstruction and chronic hepatitis showed significantly lower PaO2 and higher AaDO2 than in a control group. Dogs with chronic hepatitis also had significantly lower PaCO2. The present study shows that dogs with hepatobiliary disease have respiratory abnormalities more than healthy dogs. Preanesthetic or routine arterial blood gas analysis is likely beneficial to detect the respiratory abnormalities in dogs with hepatobiliary disease, especially extrahepatic biliary obstruction and chronic hepatitis.

A laboratory diagnostic approach to hepatobiliary disease in small animals.

Routine biochemical tests generally include serum enzymes, proteins, and other markers useful for identifying hepatobiliary disease in dogs and cats. Obtaining results outside the reference intervals can occur with direct hepatocellular injury, enzyme induction by hepatocytes or biliary epithelium, or decreased hepatic function. However, detection of biochemical abnormalities does not necessarily indicate clinically significant disease. For a comprehensive approach to detection and treatment of hepatobiliary disease, the laboratory results must be correlated with the history and physical examination findings, diagnostic imaging results, and other assays.

Fatal Wedelia glauca intoxication in calves following natural exposure.

A group of 342 beef calves, corralled in the Patagonia region of Argentina, were fed alfalfa hay that had been inadvertently contaminated with Wedelia glauca. A total of 147 (43%) calves died within 4 days. Pathologic findings in 2 calves were diffuse centrilobular hepatic necrosis and hemorrhage with edema in the gallbladder, common bile duct, and choledochoduodenal junction. Epidermal fragments of W. glauca were identified in rumen contents by microscopy. Intact W. glauca plants and leaf fragments were found in the hay. Patches of defoliated W. glauca were also identified in the alfalfa pasture from which the hay had been baled.

Morphological and molecular characterization of Explanatum explanatum from cattle and buffaloes in Myanmar.

A robust molecular marker is needed for discrimination of amphistome species, because identification based on morphology alone requires specialized knowledge and techniques. In this study, we performed morphological and molecular characterization of Explanatum explanatum, a species that causes severe liver damage in definitive host species. Fifty-five adult amphistomes were collected from cattle and water buffaloes in Myanmar. Eighteen of the amphistomes, arbitrarily chosen, were morphologically identified as E. explanatum using sagittal sections. All of the 55 amphistome isolates had identical second internal transcribed spacer (ITS2) of ribosomal DNA sequences; these sequences differed at 7 nucleotide sites from those of the closest species, Paramphistomum leydeni. Our data indicate that the ITS2 sequence could be a useful molecular marker for epidemiological studies on E. explanatum.

Coagulation in hepatobiliary disease.

OBJECTIVE: To review the pathogenesis and clinical consequences of coagulation abnormalities accompanying hepatobiliary disorders and to highlight the need for further studies to characterize these derangements and their treatment options in small animal patients. DATA SOURCES: Veterinary and human medical literature: original research articles, scientific reviews, consensus statements, and recent texts. SUMMARY: The liver plays an important role in the production and clearance of many components of coagulation. A wide range of hemostatic derangements can occur in patients with hepatobiliary disease including alterations in platelet number and function, coagulation factor levels, anticoagulants, vascular endothelial function, and fibrinolysis. As these hemostatic alterations include both pro- and anticoagulation pathways, the net result is often a rebalanced hemostatic system that can be easily disrupted by concurrent conditions resulting in either clinical bleeding or thrombosis. Conventional coagulation tests are inadequate at identifying the spectrum of coagulation alterations occurring in patients with hepatobiliary disease, but their evaluation is necessary to assess bleeding risk and provide prognostic information. A paucity of information exists regarding the treatment of the coagulation derangements in small animals with hepatobiliary disease. Extrapolation from human studies provides some information about potential treatment options, but further studies are warranted in this area to elucidate the best management for coagulation abnormalities in dogs and cats with hepatobiliary disease. CONCLUSION: Hepatobiliary disease can have profound effects on coagulation function leading to hypercoagulable or hypocoagulable states. Overall coagulation status with hepatobiliary disease depends on both the type and severity of disease and the presence of associated complications.

Choledochotomy and primary repair of extrahepatic biliary duct rupture in seven dogs and two cats.

OBJECTIVE: To report clinical findings and outcome in dogs and cats undergoing choledochotomy or primary repair of extrahepatic biliary duct rupture. METHODS: Retrospective study of dogs (n=7) and cats (n=2) that had choledochotomy or primary bile duct repair. RESULTS: Extrahepatic biliary obstruction was confirmed at surgery in all cases. The underlying cause in four dogs and both cats was choledocholithiasis, two dogs had gall bladder mucocoeles with associated bile duct rupture, and one dog had inspissated bile obstructing the bile duct secondary to gall bladder carcinoid tumour. Three dogs and both cats had choledochotomies performed to relieve extrahepatic biliary obstruction, and four dogs with bile duct rupture underwent primary repair of the defect. One dog with a bile duct rupture was re-explored four days postoperatively and had suffered dehiscence of the repair; this rupture was re-repaired. All animals were discharged from the hospital, and did not have clinical recurrence of extrahepatic biliary obstruction. CLINICAL SIGNIFICANCE: Choledochotomy and primary repair of extrahepatic biliary duct rupture were associated with low perioperative morbidity and no mortality in this small cohort of cases. These techniques are reasonable options either alone or in conjunction with other procedures when bile duct patency cannot be re-established by catheterisation or bile duct discontinuity exists.

Evaluation and treatment of a posttraumatic intrahepatic biloma in a dog.

A 9 mo old male mixed-breed dog was presented with a history of chronic vomiting and fever after undergoing a cholecystectomy for the management of traumatic cystic duct rupture associated with biliary effusion 10 days before referral. A 6 cm × 6 cm intrahepatic bile collection, a biloma, was diagnosed on abdominal ultrasound and fine-needle aspiration. The biloma was treated with percutaneous catheter drainage under ultrasonographic guidance. Two years after aspiration, the dog continued to do well.

Chronic cardiac tamponade in a cat caused by an intrapericardial biliary cyst.

A 1-year-old domestic longhair cat presented to our hospital with a 4-month history of progressive exercise intolerance and coughing. Two-dimensional echocardiography confirmed the presence of an intrapericardial cyst and cardiac tamponade. Tamponade was relieved via percutaneous aspiration of the cyst. The cyst was surgically excised 4 days later, and histopathology was consistent with a biliary cyst. The cat's clinical signs completely resolved following surgery.

Histopathological distinction and evaluation of biliary and peribiliary cysts in pig liver.

The majority of hepatic cysts identified in animals are considered to derive from the intrahepatic bile ducts (biliary cysts). An alternative origin is the peribiliary glands located in the hilum of the liver and large portal tracts (peribiliary cysts). The distinction between biliary and peribiliary cysts, and whether these have different clinical significance, has rarely been considered previously. This study reports the pathological features of five cystic porcine livers. Four of these five livers had both biliary and peribiliary cysts and the fifth had only biliary cysts. Biliary cysts were not associated with distortion of adjacent hepatic parenchyma, whereas peribiliary cysts appeared to cause local compression and circulatory disturbance. It would therefore appear that peribiliary cysts have greater potential clinical significance than those of biliary origin.

Multiple hepatic peribiliary cysts in a young pig.

Histopathologic features of hepatic peribiliary cysts were described in a young slaughtered pig. The animal was an apparently healthy 6-month-old pig of mixed breed. Macroscopically, all lobes of the liver contained numerous cysts of varying size containing serous fluid in all lobes. Histopathologically, the cysts were located mainly around the large bile duct and in the connective tissue of the portal tracts. Within serial sections, these cysts were assumed to be solitary or multilocular, but they were separated from the bile duct. The cysts were lined by a single layer of columnar, cuboidal, and flattened epithelial cells. Occasionally, goblet cells were observed. The epithelial cells were stained with periodic acid-Schiff/alcian blue and high-iron diamine/alcian blue, indicating the presence of neutral mucin, sialomucin, and sulfomucin. Grimalius' method revealed the presence of endocrine cells in the lining epithelium. There was no bile pigment in the cysts by the Hall method.

Bacterial culture results from liver, gallbladder, or bile in 248 dogs and cats evaluated for hepatobiliary disease: 1998-2003.

BACKGROUND: Information is lacking on the prevalence and susceptibility patterns of bacterial isolates in dogs and cats with suspected hepatobiliary disease. OBJECTIVES: To characterize the prevalence, identity, and antimicrobial susceptibility of common hepatobiliary isolates from such patients. ANIMALS: Dogs and cats presented to the University of Wisconsin-Madison Veterinary Medical Teaching Hospital for which samples of bile, gallbladder, or liver were submitted for culture from 1998 to 2003, including 190 dogs (192 culture episodes) and 58 cats (61 culture episodes). METHODS: Cases were identified from the microbiology laboratory database. Data from patient medical records were extracted, including the history of antimicrobial administration, the presence of fever, the results of CBC and serum biochemistry, the presence of biliary obstruction or hepatobiliary inflammation, and the results of aerobic and anaerobic bacterial cultures and aerobic antimicrobial susceptibilities. RESULTS: Biliary cultures yielded a significantly higher percentage of positive results overall (30% [18 of 60]) than did hepatic cultures (7% [15 of 215]). In patients with cholecystitis, 62% (8 of 13) had positive biliary cultures. In patients with hepatic inflammation, 23% (7 of 30) had positive bile cultures, whereas only 6% (6 of 103) had positive hepatic cultures. Escherichia coli, Enterococcus spp., Bacteroides spp., Streptococcus spp., and Clostridium spp. were the most common true-positive isolates. More than 80% of Enterobacteriaceae were susceptible to ciprofloxacin or aminoglycosides, with only 30-67% susceptible to first-generation aminopenicillins and cephalosporins. Liver samples obtained by surgery or laparoscopy were more likely to yield positive cultures than those obtained by percutaneous needle biopsy.