Hepatitis In Dogs Research Articles

Mycophenolate mofetil as a treatment for presumed idiopathic chronic hepatitis in dogs: Six cases (2010-2022).

The objectives of this study were to describe the clinical findings, treatment and outcomes of six dogs with presumed idiopathic chronic hepatitis treated with mycophenolate mofetil (MMF). Medical records were retrospectively searched to identify dogs in which idiopathic chronic hepatitis was diagnosed on histopathology between January 2010 and June 2022 that were treated with MMF for at least two weeks with >2 follow-up examinations. Data recorded from each dog included signalment, clinical signs, diagnostic test results and treatment. Six dogs were treated with MMF at a median initial dosage of 9.6mg/kg PO q 12h. Reported adverse effects from MMF included decreased appetite, vomiting and diarrhoea. In all six dogs, MMF was used successfully long term for the treatment of idiopathic chronic hepatitis as determined by 46% or greater improvement of alanine aminotransferase (ALT) between 4 and 18 weeks of starting MMF. Three dogs were also temporarily treated for 4-6 months on a tapering dose of prednisone. In two dogs, ALT remained within the reference interval, and in one dog, it was very mildly elevated when on MMF alone. In all six dogs, owners reported that the medication was well tolerated. To the authors' knowledge, this is the first report describing the use of MMF with and without a tapering dose of prednisone for the treatment of idiopathic chronic hepatitis in six dogs. Based on the outcomes of the dogs in this report, MMF can be effective for the long-term treatment of idiopathic chronic hepatitis as measured by reduction in ALT and improvement of clinical signs.

Aetiopathology of canine hepatitis in Kerala

Hepatitis in dogs could be due to infectious, toxic or metabolic causes. Among infectious causes, leptospira, canine adenovirus (CAV 1) and babesia are responsible at varying levels, depending on the local geo-climatic conditions. This study, conducted on 40 dogs with clinical signs of hepatitis in Thrissur, Kerala, revealed occurrence of 2.5 per cent (1/40) for CAV 1, 20 per cent (8/40) for leptospirosis and 22.5 per cent (9/40) for babesiosis. The aetiologies were confirmed by polymerase chain reaction (PCR) targeting the E3 gene for CAV 1, microscopic agglutination test (MAT) for leptospirosis and peripheral blood smear examination for babesiosis. Haematological profile of CAV 1 infected animals revealed thrombocytopaenia, lymphopaenia, monocytopaenia and granulocytosis. Serum biochemical analysis divulged elevated alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin and creatinine, with decreased total protein and albumin. Significant decrease in volume of packed red cells (VPRC), haemoglobin (Hb) and total erythrocyte count (TEC), with significant increase in total leukocyte count (TLC) were evident in dogs positive for leptospirosis. Serum biochemical analysis revealed significant increase in ALP, AST and blood urea nitrogen (BUN) and significant decrease in total protein. Severe anaemia and thrombocytopenia with mild leucocytosis and significant increase in ALP and total bilirubin, with hypoproteinemia were noticed in animals with babesiosis.

Can the neutrophil count from hepatic fine‐needle aspirate cytology be used to diagnose hepatitis in dogs? A pilot study

The cytologic diagnosis of inflammation on canine hepatic aspirates can be confounded by neutrophilic infiltrates in the liver of dogs with nodular regeneration, by extramedullary hematopoiesis, and by marked blood contamination. We aimed to assess the association between neutrophil counts on hepatic cytology and the histopathologic diagnosis in dogs with hepatitis and non-inflammatory hepatopathy. We also sought to determine a cut-off value for the cytologic diagnosis of hepatitis. In a retrospective blinded pilot study, three observers independently reviewed hepatic aspirates that had corresponding histopathologic examinations performed within 2days. The number of neutrophils per 200 hepatocytes was determined and averaged among observers. Only neutrophils within or directly in contact with a cluster of ≥5 hepatocytes were counted, and only intact hepatocytes within an approximate monolayer were included. Data are presented as the median (range), and the Mann-Whitney U test is used to make comparisons between groups. Eighteen cases were included (13 hepatitis and five vacuolar hepatopathy). Aspirates with a histopathologic diagnosis of hepatitis had increased numbers of neutrophils compared with those of vacuolar hepatopathy (7.7 [0.3-18.3] vs 3.0 [1.0-5.3]; P=.038). Receiver operating characteristic curve analysis indicated that ≥6 neutrophils were 61.5% (CI 31.6%-86.1%) sensitive and 100% (CI 47.8%-100%) specific for identifying hepatitis. Liver aspirates from hepatitis cases have a higher number of neutrophils on cytology compared with those from vacuolar hepatopathy; however, larger studies, including those with dogs with other liver pathologies, are required. Identification of six or more neutrophils per 200 hepatocytes is highly suggestive of hepatitis.

D-Penicillamine: The State of the Art in Humans and in Dogs from a Pharmacological and Regulatory Perspective.

Chelant agents are the mainstay of treatment in copper-associated hepatitis in humans, where D-penicillamine is the chelant agent of first choice. In veterinary medicine, the use of D-penicillamine has increased with the recent recognition of copper-associated hepatopathies that occur in several breeds of dogs. Although the different regulatory authorities in the world (United States Food and Drugs Administration—U.S. FDA, European Medicines Agency—EMEA, etc.) do not approve D-penicillamine for use in dogs, it has been used to treat copper-associated hepatitis in dogs since the 1970s, and is prescribed legally by veterinarians as an extra-label drug to treat this disease and alleviate suffering. The present study aims to: (a) address the pharmacological features; (b) outline the clinical scenario underlying the increased interest in D-penicillamine by overviewing the evolution of its main therapeutic goals in humans and dogs; and finally, (c) provide a discussion on its use and prescription in veterinary medicine from a regulatory perspective.

Lifetime diagnosis of carnivore plague

Main problem: Until now the problem of intravital direct diagnosis of canine plague (Kara's disease), aimed at detecting the viral antigen in the secretions and excretions of sick animals, remains urgent. In the case of the disease of carnivorous dogs, the issue of reliable intravital diagnosis is more urgent, since the plague of carnivores in dogs is treated. Lifetime diagnosis of this disease by methods applicable in veterinary clinics is preferable, since in the case of timely and correct diagnosis, therapeutic measures will be more effective. Purpose: To improve the system of antiepizootic measures against canine plague among dogs in terms of prevention, diagnosis and treatment of this disease. Methods: Analysis of data from private veterinary clinics reporting on the incidence of small domestic animals was used. Various serological methods were used. Differential diagnosis from infectious hepatitis in dogs was carried out by means of CBR, DPR, from parvovirus enteritis - by HIR with cat erythrocytes. To check the specificity of reactions and determine the concentration of the test material, excluding false positive results, samples of pathological material obtained from dogs with various infectious diseases, as well as those obtained from healthy intact animals, were examined. Results and their significance: The use of a complex of various diagnostic methods ensures the diagnosis of plague of carnivores in any form of the disease and at any stage, even in the case of mixed infections, as well as differentiate it from parvovirus enteritis, infectious hepatitis and other carnivorous diseases similar to plague. Valuable in the RAM for the detection of the virus-specific antigen of the plague of carnivorous virus is that it can be used to diagnose the disease in vivo by examining fecal samples and swabs from the oral and nasal cavities.

Cfa-miRNAs-122 and -21 as modern biomarkers of primary hepatitis in dogs

Primary hepatitis (PH) is one of the most frequently diagnosed hepatic diseases in dogs. Its popular forms are acute hepatitis (AH) and chronic active hepatitis (CAH) which can progress to hepatic fibrosis and cirrhosis. This investigation aimed to evaluate the use of hepatocyte released Canine familiaris miRNAs(cfamiR)-122 and -21 as serum biological markers for the early and reliable diagnosis of PH and to reveal the onset of hepatic fibrosis. After the ultrasonographic and histological examination, fifteen healthy dogs were involved in the study as control group to compare with other thirty dogs confirmed to have AH or CAH (n = 15). Activity of liver enzymes as well as serum level of globulin and total bilirubin were significantly elevated in AH (P 0.001) and CAH (P 0.01) groups whereas, serum level of total protein, albumin, BUN and A/G ratio were significantly lowered in both PH groups (P 0.01) compared to control. Cfa-miR-122 significantly expressed in AH (P 0.001) and CAH (P 0.01) and exhibited a potential significance in distinguishing these groups from control with an area under the curve (AUC) of 0.98 and 0.96, respectively. Additionally, cfa-miR-122 displayed a potential role in distinguishing AH (P 0.05) from CAH group with an AUC of 0.85. Cfa-miR-21 was only expressed in dogs of CAH group and displayed a potential role in distinguishing this group (P 0.001) from AH and healthy groups with an AUC of 0.99 and 0.88, respectively. Therefore, cfa-miR-122 can be significantly expressed in dogs with two forms of PH whereas, cfa-miR-21 could be potentially enhanced only in chronic form of PH and may act as new non-invasive biomarker for distinguishing AH from CAH.

Evaluation of COMMD1 in copper toxicosis in Labrador retrievers and Dobermans

Copper toxicosis is a major cause of hepatitis in dogs. We have shown that variants in ATP7A and ATP7B modulate hepatic copper levels in Labrador retrievers and Dobermans. However, these variants cannot fully explain the observed variation in hepatic copper levels in these dog breeds. Homozygous deletion of exon 2 of COMMD1 causes copper toxicosis in Bedlington terriers. We investigated the possible involvement of COMMD1 in the multifactorial aetiology of copper toxicosis in Labrador retrievers and Dobermans. Thirty dogs of each breed with known hepatic copper status were selected for DNA sequence analysis of the three exons and flanking intronic regions of COMMD1. The observed variants were tested for association with hepatic copper levels by linear model analysis. Several variants were observed in the DNA sequence of COMMD1 in both Labrador retrievers (nine variants) and Dobermans (11 variants) but none of these was associated with variations of hepatic copper concentrations. We conclude that COMMD1 did not play a major role in the aetiology of copper associated hepatitis in Labrador retrievers and Dobermans.

ПОШИРЕНІ ПАТОЛОГІЇ У СОБАК ТА ГЕПАТОПРОТЕКТИВНІ ЗАСОБИ

Досліджено поширення патологій гепатобіліарної системи у собак і спектр гепатозахисних препаратів. Визначено, що основна частка гепатопатій серед собак має вторинний характер – 81,8 %. Патології печінки виникають, переважно, як наслідок хронічної серцевої недостатності і токсичного навантаження організму тварин. Як самостійне захворювання, гепатопатії зареєстровано у 18,2 % собак. Встановлено, що структура гепатопротекторів для тварин сформована, в більший мірі, комбінованими препаратами – 71,4 %.

Chronic hepatitis in dogs - A histological study

Chronic hepatitis in dogs - A histological study

Infectious hepatitis in dogs (state of the problem)

The paper contains data regarding current state of research and author opinion on realization of diagnostics and therapy improvement in case of infectious hepatitis in dogs based on the form of the disease. A study of worldwide practice and a summary of personal experience of the aspects of clinical manifestation, diagnostics and treatment methods for canine hepatitis have been performed.
 According to our research canine infectious hepatitis in Sumy region is usually found in dogs at 1-3 (44%) years of age, less of ten at 5-8 (28%) years. The quantity of cases at 3-8 y.o. is 17% and in animals younger than 1 year – 11%. After being introduced into the body, the virus replicates in the regional lymph nodes then appears in the blood (viremia), after 2-3 days it forms masses of core inclusions (Rubart’s bodies) – big, round, acidophilic masses in capillary and vein endothelium in all the organs, especially liver and spleen. As a result liver dystrophy occurs and general body intoxication follows. Further development of the process results in renal and myocardial dystrophy,appearance of multiple blood effusions on mucous and serous membranes. After the neural centers of the brain and spine are being affected the locomotion disorders are observed.At the stage of acute clinical signs the virus is present in blood and all the exudates, while being observed only in kidneys and urine later. The incubation period of spontaneous hepatitis lasts about 6 to 9 days. Currently there are some cases of an acute and peracute course but chronic and latent courses are prevalent. The organ lesions depend on the severity and course of the disease. Infectious hepatitis is being diagnosed based on epizootological, clinical, pathological and laboratory study data as well as virological research and biological test. Use of a treatment regimen including polyvalent serum, anfluron, cobactan, difeniramine, metoclopramide, furosemide, hepavikel, and crystalline IV solutions allowed shorteningofthe treatment period in comparison to average.

Retrospective evaluation of cyclosporine in the treatment of presumed idiopathic chronic hepatitis in dogs.

BackgroundThe etiology of idiopathic chronic hepatitis (ICH) in dogs is poorly understood, but evidence supports an immune‐mediated pathogenesis in some dogs.ObjectivesTo describe a case series of dogs with presumed ICH treated with cyclosporine (CsA) with or without concurrent medications and to document the incidence of biochemical remission and factors associated with failure to attain remission.AnimalsForty‐eight client‐owned dogs diagnosed with presumed ICH, treatment of which included CsA.MethodsTwo‐institution, retrospective case series of dogs between 2010 and 2017. All dogs were treated with CsA with or without concurrent medications for ≥2 weeks. Data were collected from medical records.ResultsBiochemical remission (<1.1 times the upper limit of normal for alanine aminotransferase activity) was attained in 79% of dogs (38/48). Median dose of CsA at remission was 7.9 mg/kg/d (range, 2.5‐12.7 mg/kg/d) and median time to remission was 2.5 months (range, 0.75‐18 months). Concurrent hepatoprotectant treatment was not associated with likelihood of remission. Clinical score, ascites, hypoalbuminemia, hyperbilirubinemia, prolonged coagulation times, dose, and duration of treatment were not associated with the probability of remission or time to remission. Common adverse effects of CsA were gastrointestinal signs in 38% (18/48) and gingival hyperplasia in 25% (12/48) of treated dogs.Conclusion and Clinical ImportanceA treatment regimen including CsA and frequent hepatoprotectant use resulted in biochemical remission of ICH in most dogs. None of the evaluated factors, including hepatoprotectant use, were significantly associated with likelihood of remission. Future prospective studies are indicated to evaluate CsA monotherapy in ICH dogs.

Association of the canine ATP7A and ATP7B with hepatic copper accumulation in Dobermann dogs.

BackgroundHepatic copper accumulation causes chronic hepatitis in dogs. Mutations in the copper transporters ATP7A and ATP7B were, respectively, associated with attenuation and enhancement of hepatic copper concentrations in Labrador Retrievers. There is a predisposition of Dobermanns to hepatitis with increased hepatic copper concentrations.ObjectivesTo investigate whether the ATP7A:c.980C>T and ATP7B:c.4358G>A mutations identified in Labrador Retrievers were associated with hepatic copper concentrations in Dobermanns.AnimalsDobermanns from the Netherlands (n = 122) and the United States (n = 78).MethodsIn this retrospective study, mutations in ATP7A and ATP7B were investigated as risk factors for hepatic copper accumulation in Dobermanns. Liver biopsies of 200 Dobermanns were evaluated by histochemical copper staining, quantitative copper measurement, or both modalities. ATP7A and ATP7B genotypes were obtained by Kompetitive Allele Specific PCR. A linear regression model was used to investigate an association between genotype and hepatic copper concentrations.ResultsThe ATP7A:c.980C>T was identified in both Dutch (2 heterozygous individuals) and American Dobermanns. In the American cohort, the minor allele frequency of the mutation was low (.081) and a possible effect on hepatic copper concentrations could not be established from this data set. A significant association of the ATP7B:c.4358G>A variant with increased hepatic copper concentrations in Dobermanns was observed.Conclusions and Clinical ImportanceThe ATP7B:c.4358G>A variant could be a contributor to hepatic copper accumulation underlying the risk of development of copper‐associated hepatitis in breeds other than the Labrador Retriever.

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs.

This consensus statement on chronic hepatitis (CH) in dogs is based on the expert opinion of 7 specialists with extensive experience in diagnosing, treating, and conducting clinical research in hepatology in dogs. It was generated from expert opinion and information gathered from searching of PubMed for manuscripts on CH, the Veterinary Information Network for abstracts and conference proceeding from annual meetings of the American College of Veterinary Medicine and the European College of Veterinary Medicine, and selected manuscripts from the human literature on CH. The panel recognizes that the diagnosis and treatment of CH in the dog is a complex process that requires integration of clinical presentation with clinical pathology, diagnostic imaging, and hepatic biopsy. Essential to this process is an index of suspicion for CH, knowledge of how to best collect tissue samples, access to a pathologist with experience in assessing hepatic histopathology, knowledge of reasonable medical interventions, and a strategy for monitoring treatment response and complications.

Proteomic analysis of liver tissue from dogs with chronic hepatitis.

Chronic hepatitis is the most common hepatic disease in dogs. Copper accumulation is an important cause of chronic hepatitis in dogs; however, the etiology in most dogs cannot be determined. Clinical signs of chronic hepatitis are often non-specific; therefore, this disease is frequently diagnosed in an advanced stage that makes successful intervention less likely. Early diagnosis of chronic hepatitis in dogs would thus be beneficial. The identification of proteins that are differentially expressed in dogs with chronic hepatitis could contribute to the development of novel diagnostic markers for this disease and provide insight into its pathogenesis. The objective of this study was to identify novel proteins that are differentially expressed in the liver of dogs with chronic hepatitis. Hepatic tissue was collected from 8 healthy dogs during ovariohysterectomy and from 8 dogs with histologically confirmed chronic hepatitis. The proteome of the liver samples was extracted by mechanical disruption and detergent-based cell lysis and differentially labeled prior to analysis by 2-dimensional fluorescence difference gel electrophoresis. Spots with an absolute fold change value > 2.0 were selected for further analysis. Protein identification was achieved by nanoflow liquid chromatography tandem mass spectrometry. Differential expression of select proteins was validated by Western blot. Five protein spots were differentially expressed between patients with chronic hepatitis and healthy control dogs. From these 5 protein spots 11 proteins were identified. Differential expression of cytokeratin 18 and annexin 5 were confirmed by Western blot analysis. Differential protein expression was shown between dogs with chronic hepatitis and healthy control dogs. Upregulation of cytokeratin 18 in chronic hepatitis may suggest increased hepatocellular apoptosis and necrosis, whereas upregulation of annexin 5A suggests increased hepatocellular apoptosis. Further studies are needed to determine whether either protein has diagnostic utility.

Hepatic leptospiral infections in dogs without obvious renal involvement.

BackgroundReports of chronic hepatitis in dogs caused by Leptospira spp. are confined to small case series. Fluorescence in situ hybridization (FISH) allows the identification of spirochetes in liver samples. Consequently, this technique may help elucidate the role of Leptospira spp. in cases of chronic hepatitis.ObjectivesTo describe cases of hepatic leptospirosis in dogs diagnosed by FISH and subsequent polymerase chain reaction (PCR) speciation, with the absence of clinically relevant renal involvement.AnimalsTen client‐owned dogs.MethodsRetrospective case series from the University of Cambridge presented between 2013 and 2016 or cases consulted by telephone advice during this time period. Cases were selected based on histopathologically confirmed granulomatous hepatitis and leptospiral organisms identified by FISH and PCR speciation (Leptospira interrogans/kirschneri).ResultsAll cases had increased liver enzyme activities, and FISH in combination with PCR speciation‐confirmed infection with L. interrogans/kirschneri. Four dogs underwent repeat liver biopsy, FISH and PCR speciation 4‐15 months after initial presentation and doxycycline treatment with 1 dog undergoing repeat sampling at necropsy. Three dogs that underwent repeat biopsy remained positive for L. interrogans/kirschneri infection. Six dogs were alive at the time of manuscript preparation and 4 dogs were euthanized as a result of progressive liver disease.Conclusions and Clinical ImportanceThe presence of hepatic leptospiral organisms may be associated with chronic granulomatous hepatitis without clinical evidence of renal involvement. Further studies are necessary to elucidate the etiological role of these organisms in the disease.

Erythrocyte copper chaperone for superoxide dismutase and superoxide dismutase as biomarkers for hepatic copper concentrations in Labrador retrievers

Hereditary hepatic copper accumulation in Labrador retrievers leads to hepatitis with fibrosis and eventually cirrhosis. The development of a non-invasive blood-based biomarker for copper status in dogs could be helpful in identifying dogs at risk and to monitor copper concentrations during treatment. In this study, two cellular copper metabolism proteins, Cu/Zn superoxide dismutase (SOD1) and its chaperone (copper chaperone for SOD1, CCS) were measured in erythrocytes and tested for association with hepatic copper concentrations in 15 Labrador retrievers with normal or increased hepatic copper concentrations.Antibodies against CCS and SOD1 were applicable for use in canine specimens. This was demonstrated by the loss of immune-reactive bands for CCS and SOD1 in siRNA treated canine bile duct epithelial cells. Erythrocyte CCS and CCS/SOD1 ratios were decreased 2.37 (P < 0.001) and 3.29 (P < 0.001) fold in the high copper group compared to the normal copper group. Erythrocyte CCS and CCS/SOD1 ratio are potential new biomarkers for hepatic copper concentrations in Labrador retrievers and could facilitate early diagnosis and treatment monitoring for copper-associated hepatitis in dogs.

Molecular characteristics of a novel strain of canine minute virus associated with hepatitis in a dog.

A 5-year-old female Yorkshire terrier dog died a few days following hernia and ovariohysterectomy surgeries. Necropsy performed on the dog revealed that the surgeries were not the cause of death; however, degenerative viral hepatitis, showing intranuclear inclusion bodies in hepatic cells, was observed in histopathologic examination. Several diagnostic methods were used to screen for the cause of disease, and minute virus of canines (MVC) was detected in all parenchymal organs, including the liver. Other pathogens that may cause degenerative viral hepatitis were not found. Infection with MVC was confirmed by in situ hybridization, which revealed the presence of MVC nucleic acid in the liver tissue of the dog. Through sequencing and phylogenetic analysis of the nearly complete genome sequence, the strain was found to be distinct from other previously reported MVC strains. These results indicate that this novel MVC strain might be related to degenerative viral hepatitis in dogs.

Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers

Common parenchymal liver diseases in dogs include reactive hepatopathies and primary hepatitis (acute or chronic). In chronic hepatitis, there is usually a long subclinical phase. Specific clinical signs become overt only when liver damage is severe and in this phase, treatment is usually less effective. Limited data are available regarding the sensitivity of liver enzyme activity or biomarkers for early detection of subclinical hepatitis. Hepatocyte-derived microRNAs (HDmiRs) were recently identified as promising biomarkers for hepatocellular injury in multiple species. Here, the potential of the HDmiRs miR-122 and miR-148a as sensitive diagnostic biomarkers for hepatocellular injury in Labrador retrievers was investigated.Samples from 66 Labrador retrievers with histologically normal livers, high hepatic copper, and with various forms of liver injury were evaluated for serum alanine aminotransferase (ALT) activity and microRNA values. Median values of HDmiR-122 were 34.6 times higher in dogs with liver injury and high ALT than in normal dogs (95% confidence intervals [CI], 13–95; P < 0.001). HDmiR-122 values were significantly increased in dogs with liver injury and normal ALT (4.2 times; 95% CI, 2–12; P < 0.01) and in dogs with high hepatic copper concentrations and unremarkable histopathology (2.9 times; 95% CI, 1.1–8.0; P < 0.05). Logistic regression analyses demonstrated that miR-122 and miR-148a were both predictors of hepatocellular injury. The sensitivity of miR-122 was 84% (95% CI, 73–93%), making it superior to ALT (55%; 95% CI, 41–68%) for the detection of hepatocellular injury in Labrador retrievers (P < 0.001). This study demonstrated that serum HDmiR, particularly miR-122, is a highly sensitive marker for the detection of hepatocellular injury in Labrador retrievers and is a promising new biomarker that may be used for early detection of subclinical hepatitis in dogs.

Metallothionein Expression in Dogs With Chronic Hepatitis and Its Correlation With Hepatic Fibrosis, Inflammation, and Ki-67 Expression.

The chronic form of primary hepatitis occurs commonly in dogs, and the etiology is rarely found. Metallothionein (MT) is a heavy metal-binding protein found in many organs, including the liver. MT was recently shown to enhance liver regeneration and decrease hepatic fibrosis in human beings. This study examined the expression of MT in 24 cases of chronic hepatitis in dogs using immunohistochemistry. To understand the role of MT as a determinant of hepatic inflammation, fibrosis, bile duct proliferation, and regeneration, we correlated its expression with histologic lesions of chronic hepatitis, such as hepatic inflammation, fibrosis, and bile duct proliferation, as well as hepatocellular growth fraction as measured by Ki67 immunolabeling. Hepatocellular growth fraction was used as a measure of hepatic regeneration. Regression analysis revealed a significant positive correlation between MT labeling intensity and growth fraction (r(2) = 0.29, P < .05). The percentage of MT-positive cells and the overall MT expression were both positively correlated with growth fraction (r(2) = 0.25 and 0.26, respectively; P < .05). A negative correlation was found between the overall MT labeling and fibrosis (r(2) = 0.18, P < .05). A similar trend of negative correlation was also found between the percentage of MT-positive cells and fibrosis, but the P value was not statistically significant (r(2) = 0.14, P = .0684). These findings suggest a protective role of MT in dogs affected by chronic hepatitis, similar to its role in human beings. These dogs may respond to treatment modules focusing on enhancing the expression of MT.

Canine hepacivirus and idiopathic hepatitis in dogs from a Dutch cohort

Liver diseases are highly prevalent in the general dog population, though the etiology is often unknown. Recently a homolog of human hepatitis C virus was discovered in dogs with respiratory infections. Although this canine hepacivirus (CHV) was detectable in some liver samples, a clear link with liver disease has not been established. A recent study by Bexfield etal. showed that in a large cohort of dogs from the UK with idiopathic hepatitis, no evidence can be found for exposure to, or carrier state of CHV both in liver and in serum. The authors however state that 'the absence of CHV infection on dogs from the UK might not represent the global ecology of the virus'. We investigated CHV-infection in 267 liver biopsies from 120 dogs idiopathic hepatitis and 135 control animals, in a population from the Netherlands. Using a highly sensitive PCR assay for CHV-NS3, no CHV was detected in all 267 liver samples. Our data show that the lack of association between canine hepacivirus and chronic liver disease in dogs is not limited to the UK, but is also found in an independent cohort from the European continent.