Colchicine treatment in a dog with hepatoportal fibrosis

A two-year-old female spayed English setter with hepatic encephalopathy was found to have hepatoportal fibrosis and acquired portosystemic shunts on laparotomy and liver biopsy. The dog was treated symptomatically with a low-protein diet, lactulose and metronidazole, while colchicine was given as antifibrotic therapy. There was a gradual improvement in clinical signs and liver function until 30 months after first presentation, when the dog developed severe haematuria caused by renal infarction of unknown aetiology. Post mortem examination revealed hepatic fibrosis to be unchanged. This case illustrates that long term survival may be possible in canine hepatoportal fibrosis and suggests that colchicine may be effective in improving liver function and slowing progression of hepatic fibrosis.     

Plasma concentration of transforming growth factor-β1 and hepatic fibrosis in dogs

Liver fibrosis is a morphologic alteration that accompanies chronic liver diseases. Apart from analysis of liver biopsy specimens, there has been no means of diagnosing and evaluating the course of liver fibrosis in the dog. Several plasma markers, including transforming growth factor beta-1 (TGF-β1), are used to indicate liver fibrosis in humans, but none has been validated for use in dogs. There is a significant correlation between the presence and severity of hepatic fibrosis and the plasma concentration of TGF-β1 in humans with hepatic fibrosis and cirrhosis. The feasibility of using TGF-β1 as a marker for hepatic fibrosis in dogs was evaluated by comparing plasma concentrations in 29 healthy dogs and 18 dogs with liver disease. The plasma concentrations of TGF-β1, were 193 to 598 pg/mL in the healthy dogs, 143 to 475 pg/mL in the 7 dogs with mild hepatic fibrosis or none at all, and 427 to 1289 pg/mL in 11 dogs with moderate to severe hepatic fibrosis. The plasma concentrations of TGF-β1 in the dogs with moderate to severe fibrosis differed significantly (P < 0.001) from those in the other 2 groups, whereas the concentrations in the dogs with mild or no fibrosis did not differ significantly from those in the healthy dogs (P > 0.05). It was concluded that TGF-β1 is a potential plasma marker for hepatic fibrosis in dogs.     

Hepatic Fibrosis in Dogs

Hepatic fibrosis is commonly diagnosed in dogs, often as a sequela to chronic hepatitis (CH). The development of fibrosis is a crucial event in the progression of hepatic disease that is of prognostic value. The pathophysiology of hepatic fibrosis in human patients and rodent models has been studied extensively. Although less is known about this process in dogs, evidence suggests that fibrogenic mechanisms are similar between species and that activation of hepatic stellate cells is a key step. Diagnosis and staging of hepatic fibrosis in dogs requires histopathological examination of a liver biopsy specimen. However, performing a liver biopsy is invasive and assessment of fibrotic stage is complicated by the absence of a universally accepted staging scheme in veterinary medicine. Serum biomarkers that can discriminate among different fibrosis stages are used in human patients, but such markers must be more completely evaluated in dogs before clinical use. When successful treatment of its underlying cause is feasible, reversal of hepatic fibrosis has been shown to be possible in rodent models and human patients. Reversal of fibrosis has not been well documented in dogs, but successful treatment of CH is possible. In human medicine, better understanding of the pathomechanisms of hepatic fibrosis is leading to the development of novel treatment strategies. In time, these may be applied to dogs. This article comparatively reviews the pathogenesis of hepatic fibrosis, its diagnosis, and its treatment in dogs.     

Anatomicopathological study of vascular and biliary systems using cast samples of Fasciola-infected bovine livers

In 117 livers with fascioliasis, this study was focused on the number of Fasciola, the number and intrahepatic localization of affected hepatic ducts and bile ducts, and the degree of fibrosis in the hepatic segments and bile ducts. The degree of pathological changes in bile ducts caused by fascioliasis was classified into five levels. The site of Fasciola habitation was most often the hepatic ducts of the porta hepatis: it was the left hepatic duct in 101 livers and the right hepatic duct in 88 livers. Casts were prepared by infusing synthetic resin into the hepatic arterial, portal, hepatic venous and biliary systems of 15 bovine livers with fascioliasis and then examined. In the left lobe, quadrate lobe, and caudate process where atrophic fibrosis was noted, the bile ducts became rod-shaped by losing branches, and the samples resembled dead branches of liver. Portal branches were thinned or completely terminated with marked fibrosis. Fine and irregular newly formed bile ducts not parallel with portal branches were observed in livers with markedly chronic fascioliasis. Distal portal branches in the right lobe, caudate lobe, and papillary process showed hypertrophic proliferative changes. The arterial system was generally well developed in thickened walls of bile ducts and formed vascular beds, and surrounded the bile ducts as tubes. In livers with severe fibrosis, capillaries were markedly developed and resembled glass cotton.     

Multiple acquired extrahepatic portosystemic shunts secondary to veno-occlusive disease in a young German shepherd

An 11-month-old German shepherd presented with behavioral abnormalities. Histopathologic analysis of liver biopsies taken during exploratory laparotomy revealed veno-occlusive disease caused by fibrosis of the hepatic central veins leading to secondary portal hypertension, development of shunting vessels, and hepatic encephalopathy. The fibrosis was likely congenital in origin.     

Congenital hepatic fibrosis and cystic bile duct formation in Swiss Freiberger horses

Congenital hepatic fibrosis with autosomal recessive or dominant inheritance has been described in humans, cats, piglets, and dogs. In horses, only two cases of congenital hepatic fibrosis have been previously reported. This retrospective study of records from the Institute for Animal Pathology, University of Berne, identified 30 foals with liver lesions compatible with congenital hepatic fibrosis. Anamnestic data revealed clinical signs of severe liver injury in most affected animals. Pathologic examination showed severely enlarged, firm livers with thin-walled cysts. Histologically, the livers showed diffuse porto-portal bridging fibrosis with many small, irregularly formed and sometimes cystic bile ducts. All foals belonged to the Swiss Freiberger breed. Pedigree analysis revealed that the diseased animals could be traced back to one stallion. These results strongly suggest that congenital hepatic fibrosis in Swiss Freiberger horses is a recessively inherited autosomal genetic defect.     

Mild hepatic fibrosis in cholesterol and sodium cholate diet-fed rats

To date, the majority of research on hypercholesterolemia has focused on the effects of a high cholesterol diet on atherosclerosis and coronary heart disease. The toxic effects of cholesterol on the liver and the relationship between the intake of a high cholesterol diet and hepatic fibrosis, however, have not been investigated clearly or histopathologically. Male Wistar rats were fed a diet supplemented with 1.0% cholesterol and 0.3% sodium cholate for 12 weeks. Rats were sacrificed and analyzed via blood biochemistry, traditional microscopy and immunohistochemistry. Following the feeding of this diet, the rates of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and total cholesterol in the rats were elevated consistently from week 3 and throughout the remainder of the experiment. From microscopic observation, hepatic necrosis, macrophage infiltration and steatosis increased markedly throughout the experiment. Hepatic fibrosis and myofibroblast proliferation were detected at weeks 9 and 12. Mast cell appearance was proportional to the degree of hepatic damage. These findings suggest that hepatic fibrosis is inducible by a high cholesterol diet and is likely the result of the interaction between several different cell types (i.e., macrophages, myofibroblasts, and mast cells) in an inflammatory milieu. Hypercholesterolemia should be considered as a risk factor for hepatic fibrosis as well as atherosclerosis and coronary artery disease.     

Ultrasonographic findings in cattle and buffaloes with chronic hepatic fascioliosis

The purpose of this study was to characterize the ultrasonographic findings in cattle and buffaloes with chronic hepatic fascioliosis. To the best of the author's knowledge, this report is the first to document ultrasonographic findings in buffaloes with chronic hepatic fascioliosis. Ultrasonographic findings included distended gallbladders with either homogenous or heterogeneous contents, edema of the gallbladder walls, which ranged from mild or moderate to severe and bile duct mineralization. In 78% of the buffaloes, there was an ultrasonographic picture of hepatic fibrosis in which heterogeneous and hyperechogenic hepatic parenchymas with multiple echogenic foci were imaged. Other ultrasonographic findings included peritoneal, pleural and pericardial effusions. Two cows and one buffalo were slaughtered and examined postmortem. Hence, it was possible to verify distended gallbladders, edema of the gallbladder wall, calcified bile ducts, cholestasis and hepatic fibrosis by using ultrasonography in the cows and buffaloes with chronic hepatic fascioliosis. The procedure offers a useful supplement to clinical, hematological and biochemical examinations on the diagnosis of this condition.     

Mesenchymal hamartoma of the liver in a late-term equine fetus

Mesenchymal hamartoma of the liver is a rare congenital disorder of biliary tract development. During the necropsy of a late-term equine fetus, a markedly enlarged liver of more than two times normal weight was found. Light microscopic review revealed that the normal hepatic parenchyma had been obliterated, replaced, and expanded by abnormal bile ducts surrounded by abundant, myxoid stroma. The lesion was diagnosed as a mesenchymal hamartoma. Small portions of the liver had bridging septa of fibrosis and proliferations of small-caliber abnormal bile ducts, resembling another congenital biliary abnormality termed congenital hepatic fibrosis.     

Veno-occlusive disease in snow leopards (Panthera uncia) from zoological parks

Livers from 54 snow leopards, 4 days to 23 years old, that had died in 23 US zoos, were evaluated histopathologically to determine if the hepatic fibrosis, which has been noted to be prevalent in this species, was due to chronic active hepatitis from hepadnaviral infection, Ito cell proliferation, or hemosiderosis. Forty-two of 54 snow leopards had subintimal vascular fibrosis with partial or total occlusion of central and sublobular veins (veno-occlusive disease) of unknown origin. All 21 leopards older than 5 years were affected. Four leopards had chronic active hepatitis, and 12 leopards had cholangiohepatitis; but these lesions were not connected anatomically to central and sublobular venous fibrosis. Hepatocellular and Kupffer cell siderosis and Ito cell proliferation were prevalent and often coexisted with perisinusoidal, central, and sublobular venous fibrosis; but fibrosis was present in leopards without siderosis or Ito cell proliferation. The pattern and prevalence of veno-occlusive disease in these leopards was similar to that reported in captive cheetah (Acinonyx jubatus), suggesting that a common extrinsic factor may cause the majority of hepatic disease in these large felid animals in captivity.     

Toxic hepatic failure in newborn foals

Eight foals, 2 to 5 days of age, with similar clinical signs and laboratory and pathologic findings, died from hepatic failure. The predominant clinical signs were depression and icterus. Abnormally high values were found for plasma ammonia content, aromatic-to-branch-chain amino acid ratio, total serum bilirubin content, gamma glutamyl transferase activity, alkaline phosphatase activity, and PCV; partial thromboplastin time and prothrombin time were prolonged. Some foals had high sorbitol dehydrogenase activity. These laboratory findings were suggestive of subacute hepatic disease and failure. Predominant pathologic findings were limited to the liver and brain. The livers were less than half the expected size for 2- to 5-day-old foals, had prominent bile ductule proliferation, hepatic cell necrosis, and mild periportal fibrosis. These findings suggested both prenatal and postnatal diseases caused by exposure to a hepatoxin. The predominant lesion in the brain was the presence of Alzheimer type II astrocytes, which are characteristic of hepatoencephalopathy. Although the periportal fibrosis was suggestive of in utero exposure to a toxin, epidemiologic information suggested that the hepatic failure more likely resulted from oral inoculation of a microorganism culture product at birth. The same disease was reproduced in 2 newborn foals by feeding this product.     

肝纤维化动物模型研究进展

肝纤维化是肝损伤后的修复反应,涉及一系列复杂的细胞及分子机制,如何制作和选择与人类肝纤维化相似的动物模型,不仅是深入研究肝纤维化发病机制的重要基础,也是筛选防治肝纤维化药物的有效手段.文章介绍了目前常用的几种肝纤维化动物模型的造模方法,即给实验动物施以不同性质、不同剂量以及不同作用方式的肝毒剂,造成不同类型的肝纤维化模型.通过比较各种方法的致病机理、造模途径、效果、优缺点和各自用途,提出了肝纤维化动物模型的选择依据及研究方向.     

Detection of Bartonella henselae and Bartonella clarridgeiae DNA in hepatic specimens from two dogs with hepatic disease

A 4-year-old Basset Hound and a 6-year-old Doberman Pinscher were referred for diagnostic evaluation following documentation of persistently increased hepatic enzyme activities and hepatic dysfunction. Histologic evaluation of hepatic biopsy specimens from the 2 dogs revealed granulomatous hepatitis in the Basset Hound and lymphocytic hepatitis with fibrosis and copper accumulation in the Doberman Pinscher. No etiologic agents were identified histologically. Bartonella henselae DNA was subsequently amplified from hepatic tissue from the Basset Hound and Bartonella clarridgeiae was amplified from hepatic tissue from the Doberman Pinscher. Amplification was performed with a polymerase chain reaction assay incorporating primers that target a portion of the 16S-23S rRNA intergenic spacer region. Both dogs were treated with azithromycin, in combination with a variety of other medications and herbal treatments, and improved clinically. Identification of Bartonella DNA in these dogs indicates the need for future prospective studies to determine the clinical relevance of Bartonella spp infection in dogs with hepatic disease.     

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.     

Focal nodular hyperplasia in the livers of cynomolgus macaques (macaca fascicularis)

Two cases of spontaneous focal hepatic hyperplasia were observed in young female cynomolgus macaques (Macaca fascicularis). Grossly, a single raised nodule was observed in the left hepatic lobe. Histopathologically, the nodule compressed surrounding normal tissue; however, the hepatic cords within the nodule continued to those in the nor mal area except in part. Extensive fibrosis and absence of a normal hepatic triad were observed in the nodule. Thin fibrous septa radiating from the dense central stellate scarring and distended vessels were apparent in one animal. Hepatocytes in the nodule lacked cellular atypia, showed frequent PAS-positive eosinophilic inclusions in the cytoplasm and showed higher positive ratios for PCNA. The present cases resembled focal nodular hyperplasia reported in humans and a chimpanzee.     

Evaluation of serum feline trypsin-like immunoreactivity for the diagnosis of pancreatitis in cats

OBJECTIVE: To evaluate serum feline trypsin-like immunoreactivity (fTLI) concentration and results of abdominal ultrasonography, CBC, and serum biochemical analyses for diagnosis of pancreatitis in cats. DESIGN: Prospective study. ANIMALS: 28 cats with clinical signs compatible with pancreatitis. PROCEDURE: Serum fTLI concentrations were determined, and abdominal ultrasonography, CBC, and serum biochemical analyses were performed prior to histologic evaluation of pancreatic, hepatic, and intestinal specimens. On the basis of histologic results, cats were categorized as having a normal pancreas (n = 10), pancreatic fibrosis with ongoing inflammation (9), pancreatic fibrosis without inflammation (4), and acute necrotizing pancreatitis (5). Serum fTLI concentrations and results of CBC, serum biochemical analyses, and histologic evaluation of hepatic and intestinal specimens were compared among groups. RESULTS: Significant differences in serum fTLI concentrations or any hematologic or biochemical variable were not detected among the 4 groups of cats. Median serum fTLI concentrations were 51 micrograms/L (range, 18 to 200 micrograms/L) in cats with a normal pancreas, 32 micrograms/L (range, 12 to > 200 micrograms/L) in cats with pancreatic fibrosis and ongoing inflammation, 124 micrograms/L (range, 36 to > 200 micrograms/L) in cats with pancreatic fibrosis without ongoing inflammation, and 30 micrograms/L (range, 24 to 84 micrograms/L) in cats with acute necrotizing pancreatitis. We detected a high prevalence of concurrent hepatic and intestinal tract disease in cats with pancreatitis. CONCLUSIONS AND CLINICAL RELEVANCE: In cats with clinical signs of pancreatitis, serum fTLI concentration is poorly associated with histopathologic diagnosis.     

Effects of Salmonellosis on subsequent infections with Ascris suum in swine

Weanling pigs were exposed to Salmonella cholerae-suis var. kunzendorf and sixteen days later were inoculated with infective Ascaris suum eggs. Necropsy at seventeen days post-Ascaris-infection revealed fewer lesions of hepatic fibrosis and a lesser degree of tissue eosinophilia in the hepatic interstitium in pigs receiving inoculations of Salmonella and Ascaris compared to those receiving Ascaris inoculation only. The numbers of juvenile nematodes recovered from the small intestines of both groups were variable. The comparatively less-intensive hepatic lesions may have been caused by reduction of the number of penetrating larvae at the intestinal level. Alternatively, the decreased tissue eosinophilia and fibrosis of the liver may be due to the previous stress of the Salmonella infection.     

Hepatic encephalopathy in a pregnant mare: identification of histopathological changes in the brain of a mare and fetus

An 11-year-old Thoroughbred broodmare was evaluated for suspected hepatic dysfunction. Clinical signs of hepatic encephalopathy were evident at admission. Hepatic ultrasonographic evaluation revealed an increase in hepatic size, rounded borders and normal echogenicity. There was no evidence of cholelithiasis or bile duct distention. Increased activity of hepatic enzymes, increased bile acid and bilirubin concentration and an increased ammonia concentration were supportive of a diagnosis of hepatic disease and hepatic encephalopathy. Histopathological evaluation of a liver biopsy specimen was consistent with chronic active hepatitis. The mare was treated with intravenous fluids and antimicrobials, pentoxyfilline, branched-chain amino acids and dietary manipulation. Clinical improvement was observed initially; however, 3 weeks later, deterioration in the mare's condition necessitated euthanasia. Pathological lesions at necropsy were restricted to the liver and brain. The liver was diffusely firm with a prominent reticular pattern on the cut surface. A large choledocholith was present in the main bile duct of the left liver lobe. Histopathological examination of the liver revealed severe fibrosis, with hyperplastic bile ducts and mononuclear and neutrophilic inflammation. Pathological changes consistent with hepatic encephalopathy, (Alzheimer type II cells), were evident in the cerebrum of both the mare and the fetus.     

Lack of associations between ultrasonographic appearance of parenchymal lesions of the canine liver and histological diagnosis

Objective: To assess if there are any ultrasonographic features that may enable tentative diagnosis of hepatic parenchymal disease. Methods: Records of 371 dogs that had abdominal ultrasonography and abnormal liver on biopsy or necropsy were reviewed. Results: Histological diagnoses were hepatitis (n=77), nodular hyperplasia (n=47), vacuolar change (n=45), fibrosis (n=32), primary hepatic carcinoma (n=30), lymphoma (n=28), metastatic neoplasia (n=27), necrosis (n=21), lipidosis (n=17), haemangiosarcoma (n=13), round cell tumour (n=9), hepatocellular adenoma (n=8), degenerative change (n=6), steroid hepatopathy (n=7) and extramedullary haematopoiesis (n=4). The most prevalent ultrasonographic features were multifocal lesions (63% livers with haemangiosarcoma and 43% livers with hepatocellular carcinoma), diffuse lesions (71% livers with steroid hepatopathy, 44% livers with fibrosis and 40% livers with vacuolar hepatopathy), hyperechoic lesions (71% livers with steroid hepatopathy, 41% livers with lipidosis and 38% livers with fibrosis), heterogeneous lesions (62% livers with haemangiosarcoma), hepatomegaly (43% livers with steroid hepatopathy) and peritoneal fluid (62% livers with haemangiosarcoma). Target lesions were associated with malignancy in 67% instances. Marked variability in ultrasonographic appearance of lesions was observed for all diagnoses, and no statistically significant associations between ultrasonographic appearance and diagnosis were found. Clinical Significance: Histological examination remains essential for diagnosis of canine hepatic disease.