Jonathan A. Lidbury

New advances in the diagnosis of canine and feline liver and pancreatic disease

The diagnosis of liver and pancreatic disorders in dogs and cats present their own set of challenges. However, as new diagnostic tests are developed and the optimal ways in which to use existing tests are determined, the ability of the veterinary profession to make these diagnoses continues to improve. Histopathological assessment is considered to be the reference standard for the diagnosis of many hepatic and pancreatic diseases, but it has some inherent limitations. New classes of diagnostic tests for liver disease that are currently being studied include direct and indirect serum markers of hepatic fibrosis, such as hyaluronic acid; novel markers of hepatocellular injury, such as circulating microRNAs; and quantitative tests of hepatic microsomal function. Assays for pancreas-specific lipase have greatly improved the ability of practitioners to diagnose pancreatitis in dogs and cats. However, further research is needed to fully understand the characteristics of these assays, especially in patients with concurrent non-pancreatic disease. The more common use and refinement of CT and MRI to assess the hepatobiliary system and pancreas of dogs and cats also have huge potential to improve diagnostic capabilities.

Assessment of the Variation Associated with Repeated Measurement of Gastrointestinal Transit Times and Assessment of the Effect of Oral Ranitidine on Gastrointestinal Transit Times Using a Wireless Motility Capsule System in Dogs

This study aimed to evaluate the variation associated with repeated measurement of gastrointestinal (GI) transit times and the effect of oral ranitidine on GI transit times in healthy dogs using a wireless motility capsule (WMC) system. Eight privately owned healthy adult dogs were enrolled, and one developed diarrhea and was removed from the study. For the first 3 repetitions, each dog was fed a standard meal followed by oral administration of a WMC. For the 4th repetition, each dog was given ranitidine hydrochloride (75 mg PO every 12 hours) prior to and during assessment of GI transit times. Mean between-subject coefficients of variation for gastric emptying time (GET), small and large bowel transit time (SLBTT), and total transit time (TTT) were 26.9%, 32.3%, and 19.6%, respectively. Mean within-subject coefficients of variation for GET, SLBTT, and TTT were 9.3%, 19.6%, and 15.9%, respectively. Median GET, SLBTT, and TTT without ranitidine were 719, 1,636, and 2,735 minutes, respectively. Median GET, SLBTT, and TTT with ranitidine were 757, 1,227, and 2,083 minutes, respectively. No significant differences in GI transit times were found between any of the 4 repetitions. Under these experimental conditions, no significant effects of oral ranitidine on GI transit times were observed.

Hepatic encephalopathy in dogs and cats

Objective To comparatively review the pathogenesis, clinical presentation, diagnosis, and management of hepatic encephalopathy (HE) in dogs and cats. Data Sources The Medline database was searched for articles related to HE in people, dogs, and cats. Articles published within the last 5 years were given special importance. Human Data Synthesis The pathogenesis of HE is complex and incompletely understood, but ammonia appears to play a central role. Hyperammonemia leads to accumulation of glutamine in astrocytes, with subsequent astrocyte swelling and neurological dysfunction. The development of HE in patients with hepatic cirrhosis is a poor prognostic indicator. The fermentable disaccharide lactulose and the antimicrobial rifaximin are US Food and Drug Administration approved treatments for human HE. Severe protein restriction is no longer recommended for patients with this condition. Veterinary Data Synthesis HE is often associated with portosystemic shunting in dogs and cats. Ammonia plays a central role in the pathogenesis of HE in dogs and cats, but other factors such as manganese and endogenous benzodiazepines may also contribute. Recently, a soy protein-based diet was found to be beneficial in treating canine HE. Severe dietary protein restriction is likely to be detrimental in affected animals. There have been no clinical trials of drugs routinely used in the management HE in veterinary medicine, but lactulose and antimicrobials such as metronidazole are well-established treatments. Conclusions HE is a potentially life-threatening condition that is probably underdiagnosed in companion animals. Although various treatment recommendations have been proposed, there is a lack of evidence in the veterinary literature regarding optimal strategies for the management of this condition. As our understanding of the pathogenesis of HE in dogs and cats evolves, novel diagnostic tests and therapeutic agents may become available.OBJECTIVE To comparatively review the pathogenesis, clinical presentation, diagnosis, and management of hepatic encephalopathy (HE) in dogs and cats. DATA SOURCES The Medline database was searched for articles related to HE in people, dogs, and cats. Articles published within the last 5 years were given special importance. HUMAN DATA SYNTHESIS The pathogenesis of HE is complex and incompletely understood, but ammonia appears to play a central role. Hyperammonemia leads to accumulation of glutamine in astrocytes, with subsequent astrocyte swelling and neurological dysfunction. The development of HE in patients with hepatic cirrhosis is a poor prognostic indicator. The fermentable disaccharide lactulose and the antimicrobial rifaximin are US Food and Drug Administration approved treatments for human HE. Severe protein restriction is no longer recommended for patients with this condition. VETERINARY DATA SYNTHESIS HE is often associated with portosystemic shunting in dogs and cats. Ammonia plays a central role in the pathogenesis of HE in dogs and cats, but other factors such as manganese and endogenous benzodiazepines may also contribute. Recently, a soy protein-based diet was found to be beneficial in treating canine HE. Severe dietary protein restriction is likely to be detrimental in affected animals. There have been no clinical trials of drugs routinely used in the management HE in veterinary medicine, but lactulose and antimicrobials such as metronidazole are well-established treatments. CONCLUSIONS HE is a potentially life-threatening condition that is probably underdiagnosed in companion animals. Although various treatment recommendations have been proposed, there is a lack of evidence in the veterinary literature regarding optimal strategies for the management of this condition. As our understanding of the pathogenesis of HE in dogs and cats evolves, novel diagnostic tests and therapeutic agents may become available.

A dysbiosis index to assess microbial changes in fecal samples of dogs with chronic inflammatory enteropathy

ABSTRACT Recent studies have identified various bacterial groups that are altered in dogs with chronic inflammatory enteropathies (CE) compared to healthy dogs. The study aim was to use quantitative PCR (qPCR) assays to confirm these findings in a larger number of dogs, and to build a mathematical algorithm to report these microbiota changes as a dysbiosis index (DI). Fecal DNA from 95 healthy dogs and 106 dogs with histologically confirmed CE was analyzed. Samples were grouped into a training set and a validation set. Various mathematical models and combination of qPCR assays were evaluated to find a model with highest discriminatory power. The final qPCR panel consisted of eight bacterial groups: total bacteria, Faecalibacterium, Turicibacter, Escherichia coli, Streptococcus, Blautia, Fusobacterium and Clostridium hiranonis. The qPCR‐based DI was built based on the nearest centroid classifier, and reports the degree of dysbiosis in a single numerical value that measures the closeness in the l2 ‐ norm of the test sample to the mean prototype of each class. A negative DI indicates normobiosis, whereas a positive DI indicates dysbiosis. For a threshold of 0, the DI based on the combined dataset achieved 74% sensitivity and 95% specificity to separate healthy and CE dogs.

A Prospective, Placebo‐Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats

Background Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. Objectives Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. Animals Six healthy adult DSH cats. Methods In a within subjects, before and after design, cats received placebo followed by omeprazole (0.83–1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two‐way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole. Results No significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole. Conclusions and Clinical Importance Although further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats.

Gastric histopathologic abnormalities in dogs: 67 cases (2002–2007)

OBJECTIVE To test the hypothesis that intestinal pathologic changes are often concurrent with gastric pathologic changes in dogs and to characterize the historical, physical, clinicopathologic, imaging, and endoscopic findings in dogs with gastric histopathologic abnormalities. DESIGN Retrospective case series. ANIMALS 67 dogs with gastric histopathologic abnormalities. PROCEDURES Medical records from dogs that had undergone gastrotomy, gastroduodenoscopy, or gastroscopy between September 2002 and September 2007 were identified. Dogs were included in the study when histopathologic abnormalities were detected during evaluation of gastric tissue sections. History, clinical examination findings, results of diagnostic tests, diagnoses, treatments, and outcome were recorded for each dog. RESULTS 67 dogs with gastric histopathologic abnormalities were included in the study. The most frequent clinical sign recorded was vomiting (36/67 [53.7%] dogs). The most common biochemical abnormality recorded was panhypoproteinemia (27/64 [42.2%] dogs). Lymphoplasmacytic gastritis was the most frequent histopathologic finding recorded (34/67 [50.7%] dogs). For dogs in which both intestinal biopsy specimens and gastric biopsy specimens were collected, concurrent pathologic changes were recorded in 43 of 60 (71.7%) dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results of this study suggested that intestinal pathologic changes are commonly concurrent in dogs with gastric pathologic changes. This supports the practice of collecting both gastric and duodenal biopsy specimens every time gastroduodenoscopy is performed. Lymphoplasmacytic gastritis was the most commonly recorded gastric histopathologic finding and was often of minimal or mild severity.

Variation of the microbiota and metabolome along the canine gastrointestinal tract

IntroductionThe fecal microbiota are relevant to the health and disease of many species. The importance of the fecal metabolome has more recently been appreciated, but our knowledge of the microbiota and metabolome at other sites along the gastrointestinal tract remains deficient.ObjectiveTo analyze the gastrointestinal microbiota and metabolome of healthy domestic dogs at four anatomical sites.MethodsSamples of the duodenal, ileal, colonic, and rectal contents were collected from six adult dogs after humane euthanasia for an unrelated study. The microbiota were characterized using Illumina sequencing of 16S rRNA genes. The metabolome was characterized by mass spectrometry-based methods.ResultsPrevalent phyla throughout the samples were Proteobacteria, Firmicutes, Fusobacteria, and Bacteroidetes, consistent with previous findings in dogs and other species. A total of 530 unique metabolites were detected; 199 of these were identified as previously named compounds, but 141 of them had at least one significantly different site-pair comparison. Noteworthy examples include relative concentrations of amino acids, which decreased from the small to large intestine; pyruvate, which peaked in the ileum; and several phenol-containing carboxylic acid compounds that increased in the large intestine.ConclusionThe microbiota and metabolome vary significantly at different sites along the canine gastrointestinal tract.

Prevalence and Clinicopathological Features of Triaditis in a Prospective Case Series of Symptomatic and Asymptomatic Cats

Background The term triaditis designates the concurrent presence of idiopathic inflammatory bowel disease (IBD), cholangitis, and pancreatitis in cats. Hypothesis/Objectives The histopathology of concurrent, but often subclinical, inflammatory processes in the small intestine, liver, and pancreas of cats is poorly described. We aimed to investigate the frequency of enteritis, cholangitis, pancreatitis, or some combination of these in symptomatic and asymptomatic cats, compare clinicopathological features, and correlate histopathological with laboratory findings. Animals Domestic cats (27 symptomatic, 20 asymptomatic, and 8 normal). Methods Prospective study. Physical examination, laboratory variables (CBC, serum biochemistry profile, serum thyroxine concentration, serum feline trypsin‐like immunoreactivity [fTLI], feline lipase immunoreactivity [fPLI, as measured by Spec fPL ®], urinalysis, and fecal analysis), imaging, and histopathological examinations were conducted. Feline liver, pancreas, and small intestine were biopsied during laparotomy. Results Inflammatory lesions were detected in 47 cats (27 symptomatic, 20 asymptomatic). In total, 20 cats had histopathologic lesions of IBD (13/47, 27.7%), cholangitis (6/47, 12.8%), or pancreatitis (1/47, 2.1%) alone, or inflammation involving >1 organ (27/47, 57.4%). More specifically, 16/47 cats (34.0%) had concurrent lesions of IBD and cholangitis, 3/47 (6.4%) of IBD and pancreatitis, and 8/47 cats (17%) of triaditis. Triaditis was identified only in symptomatic cats (8/27, 29.6%). A mild, positive correlation was detected between the severity (score) of IBD lesions and the number of comorbidities (rho = +0.367, P = .022). Conclusions and Clinical Importance Histopathological evidence of IBD or IBD with comorbidities was detected in both symptomatic and asymptomatic cats. The possibility of triaditis should be considered in symptomatic cats with severe IBD.

Getting the Most Out of Liver Biopsy.

Histopathologic evaluation of liver biopsy specimens yields information that is not otherwise obtainable and is frequently essential for diagnosing hepatic disease. Percutaneous needle biopsy, laparoscopic biopsy, and surgical biopsy each have their own set of advantages and disadvantages. Care should be taken to ensure an adequate amount of tissue is collected for meaningful histologic evaluation. Because sampling error is a limitation of hepatic biopsy, multiple liver lobes should be biopsied. This article discusses the indications for liver biopsy, associated risks, advantages and disadvantages of different biopsy techniques, and strategies to get the most useful information possible out of this process.

Interobserver Agreement Using Histological Scoring of the Canine Liver

Background Grading schemes for the assessment of hepatic fibrosis and necroinflammatory activity in humans previously have been applied to dogs with chronic hepatitis. Interobserver agreement is a desirable characteristic for any histological scoring scheme. Hypothesis/Objectives To assess interobserver agreement associated with pathologists using a previously published histological scoring scheme to assess hepatic fibrosis and necroinflammatory activity in dogs and to compare fibrosis scores assigned to serial sections stained with hematoxylin & eosin (H&E) and picrosirius red. Animals Histological sections of liver from 50 dogs with variable degrees of hepatic fibrosis and necroinflammatory activity were selected from institutional tissue archives. Methods Six board‐certified veterinary anatomic pathologists assigned fibrosis and necroinflammatory activity scores to the histological sections. The multiuser kappa statistic was calculated to assess interobserver agreement. Fibrosis stage assigned to serial sections stained with picrosirius red and H&E was compared using the Wilcoxon signed‐rank test. Results Multiuser kappa statistics for assessment of fibrosis and necroinflammatory activity from H&E‐stained sections were 0.35 and 0.16, respectively. There was no difference in median fibrosis scores assigned to serial section stained with H&E and picrosirius red (P = .248). Conclusions and Clinical Importance There was fair interobserver agreement when pathologists assessed fibrosis and poor agreement when they assessed necroinflammatory activity. This suboptimal agreement must be taken into account by clinicians making decisions based on histology reports of the liver and in the design of studies evaluating these findings. To decrease this variability, ideally >1 pathologist should evaluate each section.