Pathology of "double scale" skin defect in farmed American alligators (Alligator mississippiensis) and the possible association with hepatic fibrosis.

"Double scale" is a poorly characterized skin defect of crocodilians that drastically reduces the economic value of crocodilian skin. This study investigated the morphology and pathogenesis of double scale in a ranching farm of American alligators (Alligator mississippiensis). We compared the histopathology of skin and selected organs (liver, lung, kidney, heart, spleen, intestine, and brain) of alligators with double scale against healthy control animals, together with serum and liver vitamin and mineral levels. Skin affected with double scale had statistically significant hyperkeratosis, epidermal atrophy, and increased basal cell degeneration compared with control alligators (P < .0001). Interestingly, all alligators with double scale had varying degrees of hepatic fibrosis. Feed analysis showed that alligators that had double scale and hepatic fibrosis had prolonged dietary exposure to high levels of vitamin A, iron, and copper. Serum analysis indicated that levels of zinc (p < .0001), copper (P < .05), and vitamin E (P < .002) were significantly lower in alligators with hepatic fibrosis and double scale compared with controls. Finally, immunohistochemical analysis of skin with double scale showed a marked reduction in immunolabeling with the zinc-binding protein metallothionein. These results suggest that zinc deficiency, in combination with other micronutrient anomalies, may play a role in the pathogenesis of double scale in alligators with liver fibrosis.

Liver fibrosis in fish research: From an immunological perspective.

Liver fibrosis is a pathological process whereby the liver is subjected to various acute and chronic injuries, resulting in the activation of hepatic stellate cells (HSCs), an imbalance of extracellular matrix generation and degradation, and deposition in the liver. This review article summarizes the current understanding of liver fibrosis in fish research. Liver fibrosis is a common pathological condition that occurs in fish raised in aquaculture. It is often associated with poor water quality, stressful conditions, and the presence of pathogens. The review describes the pathophysiology of liver fibrosis in fish, including the roles of various cells and molecules involved in the development and progression of the disease. The review also covers the various methods used to diagnose and assess the severity of liver fibrosis in fish, including histological analysis, biochemical markers, and imaging techniques. In addition, the article discusses the current treatment options for liver fibrosis in fish, including dietary interventions, pharmaceuticals, and probiotics. This review highlights the need for more in-depth research in this area to better understand the mechanisms by which liver fibrosis in fish occurs and to develop effective prevention and treatment strategies. Finally, improved management practices and the development of new treatments will be critical to the sustainability of aquaculture and the health of farmed fish.

Liver fibrosis is a common pathological change in the liver of dairy cows with fatty liver.

Fatty liver (i.e., hepatic lipidosis) is a prevalent metabolic disorder in dairy cows during the transition period, characterized by excess hepatic accumulation of triglyceride (TG), tissue dysfunction, and cell death. Detailed pathological changes, particularly hepatic fibrosis, during fatty liver remain to be determined. Liver fibrosis occurs as a consequence of liver damage, resulting from the excessive accumulation of extracellular matrix, which distorts the architecture of the normal liver, compromising its normal synthetic and metabolic functions. Thus, we aimed to investigate liver fibrosis status and its potential causal factors including oxidative stress, hepatocyte apoptosis, and production of inflammatory cytokines in the liver of cows with fatty liver. Forty-five dairy cows (parity, 3-5) were selected, and liver biopsy and blood were collected on the second week postpartum (days in milk, 10-14 d). On the basis of the degree of lipid accumulation in liver, selected cows were categorized into normal (n = 25; TG <1% wet wt), mild fatty liver (n = 15; 1% ≤ TG <5% wet wt), and moderate fatty liver (n = 5; 5% ≤ TG <10% wet wt). Compared with normal cows, blood concentrations of nonesterified fatty acids and ß-hydroxybutyrate, along with alanine aminotransferase and aspartate aminotransferase activities, were greater in the cows with fatty liver (mild and moderate). Hepatic extracellular matrix deposition, as indicated by Picrosirius red staining, was greater in cows with fatty liver than those with normal ones. In addition, we observed an increased proportion of collagen type I fiber in extracellular matrix with increased lipid accumulation in the liver. Compared with normal cows, the area of α-smooth muscle actin (α-SMA)-positive staining along with the mRNA abundance of collagen type I α 1 (COL1A1), ACTA2 (gene encoding α-SMA), and transforming growth factor-ß (TGFB) were greater in cows with fatty liver. Compared with normal cows, hepatic contents of malondialdehyde, glutathione disulfide, and 8-isoprostane were greater, whereas total antioxidant capacity, the hepatic content of glutathione, and activities of antioxidant indicators, including superoxide dismutase, glutathione peroxidase, and catalase, were lower in cows with fatty liver. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells and abundance of apoptosis-related molecules BAX, CASP3, CASP8, and CASP9 were greater in cows with fatty liver. However, mRNA abundance of the anti-apoptotic gene BCL2 did not differ. The mRNA abundance of pro-inflammatory cytokines including tumor necrosis factor-α (TNFA), interleukin-1ß (IL1B), and interleukin-6 (IL6) was greater in the liver of cows with fatty liver. Overall, the present study indicated that fibrosis is a common pathological response to liver damage and is associated with oxidative stress, hepatocyte death, and inflammation.

Shear wave velocity values measured by 2D-shear wave elastography are not different between awake and anesthetized cats without clinically significant hepatic fibrosis.

Two-dimensional shear wave elastography (2D-SWE) is widely used as a noninvasive method to quantify liver stiffness. In humans, liver stiffness approximates histologic hepatic fibrosis. While histology is the gold standard for diagnosing liver disease, 2D-SWE may be a minimally invasive alternative to biopsy in feline patients. The objectives of this prospective, observational, crossover study were trifold: (1) to assess the feasibility of performing 2D-SWE in awake cats, (2) to determine whether anesthesia altered shear wave velocity (SWV) measurements, and (3) to correlate hepatic stiffness with histologically quantified hepatic fibrosis. Eleven healthy, purpose-bred cats underwent 2D-SWE in awake and anesthetized states. SWV measurements were compared with histologic fibrosis measurements obtained from liver biopsies during the anesthetic period. The mean velocities were not significantly different between awake (1.47 ± 0.18 m/s) and anesthetized (1.47 ± 0.24 m/s) cats. Premedication and anesthetic drugs did not impact mean SWV. There was a higher variability in the SWV values in the awake group. The data points were reliably replicated, with an interquartile range of 0.24 and 0.32 in anesthetized and awake groups, respectively. There was moderate agreement between observers (intraclass correlation coefficient = 0.66). All cats had clinically insignificant fibrosis. There was no correlation between the SWV measurements and the histological fibrosis values. This study demonstrates that 2D-SWE is feasible in awake cats and that the anesthetic protocol employed did not significantly alter mean SWV. This work is the first to histologically validate normal SWV values in cats and show that 2D-SWE cannot differentiate minimal differences in feline hepatic fibrosis.

Hepatic fibrosis and mineralization in a free-ranging barren-ground caribou (Rangifer tarandus groenlandicus) from the Northwest Territories.

Due to concerns about the appearance of portions of liver from a harvested adult, male barren-ground caribou (Rangifer tarandus groenlandicus), samples were submitted for diagnostic investigation. The gross and histologic findings were consistent with severe hepatic fibrosis and mineralization. Concentrations of vitamin E in the liver were also deficient. Disease investigations in wildlife of detectable abnormalities such as this provide important information for understanding the role of disease as populations change, as well as for safety of human food sources.

Fibrose hépatique et minéralisation chez un caribou de la toundra ( Rangifer tarandus groenlandicus ) en liberté provenant des Territoires du Nord-Ouest. En raison de préoccupations concernant l'apparence de portions de foie provenant d'un caribou de la toundra mâle adulte (Rangifer tarandus groenlandicus), des échantillons ont été soumis à des fins d'enquête diagnostique. Les résultats macroscopiques et histologiques étaient compatibles avec une fibrose hépatique sévère et une minéralisation. Les concentrations de vitamine E dans le foie étaient également déficientes. Les enquêtes sur les maladies de la faune sauvage portant sur des anomalies détectables telles que celle-ci fournissent des informations importantes pour comprendre le rôle des maladies à mesure que les populations changent, ainsi que pour la sécurité des sources de nourriture humaine.(Traduit par Dr Serge Messier).

Long-term follow-up of portal vein thrombosis in an American Cocker Spaniel with lobular dissecting hepatitis: a case report.

BACKGROUND: Lobular dissecting hepatitis (LDH) is a rare form of canine liver cirrhosis that may be accompanied by portal hypertension in American Cocker Spaniels. In human patients with liver cirrhosis, portal vein thrombosis (PVT) is a common complication. However, PVT has not been reported in dogs with LDH. Herein, we describe the long-term follow-up of PVT in an American Cocker Spaniel with LDH. CASE PRESENTATION: An 8-year-old neutered male American Cocker Spaniel presented with a 1-month history of severe abdominal effusion. The dog was histopathologically diagnosed with LDH and treated with low-dose prednisolone on day 14. On day 115, computed tomography angiography (CTA) confirmed the presence of a thrombus in the portal vein. Therefore, the dog was subcutaneously administered with the anticoagulant dalteparin, and low-dose prednisolone was continued. As a follow-up for PVT, CTA examinations were performed on days 207, 515, 886, and 1168, and the dog's antithrombin and D-dimer levels were measured. Following anticoagulant therapy, the dog was confirmed to have gradually increased antithrombin activity and decreased D-dimer concentrations. In addition, although the thrombus was confirmed to be in the same area of the portal vein system by CTA, atrophy and increased CT values due to organization were observed during the follow-up period. The dog's condition remained stable without clinical signs until day 1112 when it developed hepatic encephalopathy. The dog died on day 1208. On postmortem examination, histopathologically, the liver showed marked bile duct hyperplasia and fibrosis with chronic thrombus in the portal vein. CONCLUSIONS: This case demonstrated that low-dose glucocorticoid combined with dalteparin allowed long-term follow-up of PVT in an American Cocker Spaniel with LDH.

A study on causes of cattle liver condemnation at an abattoir in Omdurman area, Khartoum State, Sudan.

BACKGROUND: Information obtained from abattoirs on the causes of liver condemnation is important in preventing the spread of diseases and for promoting food security. The current study reviews three years (2009 to 2011) postmortem inspection records of cattle slaughtered at an abattoir in Omdurman, Khartoum State, Sudan. The aim was to determine the prevalence of diseases and conditions that lead to liver condemnation. RESULTS: From a total of 234,175 cattle slaughtered, 8,910 (3.8%) livers were condemned due to several diseases/conditions mainly fasciolosis, cysticercosis, necrosis, abscess, calcification, hemorrhages, liver cirrhosis, hydatidosis, and other miscellaneous causes. Collectively, fasciolosis was the leading cause of liver condemnation and was responsible for 51.6 % of total liver condemnations followed by necrosis (18.6%), and cysticercosis (13.5%). CONCLUSIONS: Because of their zoonotic nature, the observed high frequency of some detected diseases/conditions is thought to pose a public health risk among consumers. This survey could be used as a regional baseline for future monitoring of control programmers against these liver diseases.

Extrahepatic biliary obstruction can interfere with hepatic fibrosis prediction using two-dimensional shear wave elastography in dogs.

Two-dimensional shear wave elastography (2D-SWE) can be used to quantitatively evaluate the elastic modulus of the liver as shear wave velocity (SWV), which can noninvasively predict clinically relevant hepatic fibrosis in both dogs and humans. However, extrahepatic biliary obstruction (EHBO), regardless of the presence of clinically relevant hepatic fibrosis, can influence SWVs in humans and thus may interfere with hepatic fibrosis prediction using 2D-SWE in dogs. The aim of this prospective, observational, and one-group pretest-posttest study is to investigate whether SWV measured by 2D-SWE displays a difference between dogs with and without EHBO. A total of 20 dogs were included (7 with EHBO and 13 with gallbladder pathology but no EHBO) that underwent preoperative SWV measurement using 2D-SWE. In all dogs, stages of hepatic fibrosis were evaluated histopathologically using a scoring scheme. In addition, postoperative SWVs in dogs with EHBO relieved via laparotomy were also evaluated. The median (range) SWVs in the dogs with and without EHBO were 1.91 (1.81-2.54) m/s and 1.57 (1.37-1.64) m/s, respectively. Although there was no significant difference in the histopathological hepatic fibrosis stages between the dogs with and without EHBO, the preoperative SWVs in the dogs with EHBO were significantly higher than in dogs without EHBO (P = .0004), and SWVs were found to decrease significantly after surgery (P = .0097). This study demonstrates that EHBO can increase the SWV of dogs without clinically relevant hepatic fibrosis and can interfere with the prediction of noninvasive hepatic fibrosis using 2D-SWE.

Predicting copper toxicosis: relationship between the ATP7A and ATP7B gene mutations and hepatic copper quantification in dogs.

This preliminary study summarizes the genotypes of 42 Labrador Retrievers and Labrador Retriever-Golden Retriever crosses and phenotypes a subset of ten of these dogs that are homozygous mutant, heterozygous, or homozygous normal for mutations in the ATP7A and ATP7B genes that have been associated with the development of copper toxicosis in Labrador Retrievers. The purpose of this study is to evaluate whether there is a correlation between ATP7A and ATP7B genotypes and clinical evidence of hepatic pathology in young, asymptomatic Labrador Retrievers. We evaluated serum ALT levels, hepatic copper concentrations, and hepatic histopathology from ten offspring where both parents had a least one copy of the ATP7B mutation. Five were homozygous mutant, four were heterozygous, and one was homozygous normal for comparison. None had increased serum ALT activity. All dogs homozygous for the ATP7B mutation had elevated hepatic copper concentrations compared to dogs heterozygous for the ATP7B mutation regardless of sex or presence of an ATP7A mutation with the mean hepatic copper concentration being 1464 ppm (reference range 100-330 ppm). Mean hepatic copper concentration in homozygous normal and heterozygous dogs was 328 ppm. In this preliminary analysis, we found that dogs that carry two copies of the ATP7B mutation have abnormally elevated hepatic copper levels despite having normal serum ALT activity. Our findings support the hypothesis that the ATP7B DNA test can predict defects in hepatic copper metabolism. Veterinarians can test for the ATP7B gene mutation to identify Labrador Retrievers at risk for copper toxicosis so that they can take steps to prevent development of copper-associated chronic hepatitis in their patients.

Congenital Hepatic Fibrosis in a Purebred Spanish Horse Foal: Pathology and Genetic Studies on PKHD1 Gene Mutations.

A 1-month-old Purebred Spanish Horse (PSH) foal presented with progressive hepatic failure culminating in death. Hepatic lesions were consistent with congenital hepatic fibrosis (CHF). Genetic studies in the PKHD1 gene in the affected foal revealed that it was heterozygous for the 2 previously described single-nucleotide polymorphisms (SNPs) linked to CHF in Swiss Franches-Montagnes (SFM) horses. In addition, 2 novel mutations were detected, the foal being homozygous for one of them and heterozygous for the other. Genetic studies in a healthy PSH population ( n = 35) showed a 3-fold higher genotypic frequency for PKHD1 SNP g.49,630,834G>A and a 5-fold higher genotypic frequency for PKHD1 SNP g.49,597,760A>T compared with those reported for SFM horses. SNPs in the PKHD1 gene in CHF-affected SFM horses might not fully explain the CHF observed in the PSH. Other mutations in the PKHD1 gene could play a more important role in the PSH.

Hepatic Dicrocoelium dendriticum infection in a miniature horse.

A miniature horse which died following humane seizure from an Ontario farm was emaciated with serous atrophy of fat. Autopsy revealed hepatic atrophy and moderate periportal fibrosis. Eggs and trematodes seen in the liver were identified as Dicrocoelium dendriticum. This appears to be the first reported case of infection of equids in North America with Dicrocoelium dendriticum.

Infection parDicrocoelium dendriticumhépatique chez un cheval miniature. Un cheval miniature qui est mort à la suite d'une saisie humanitaire dans une ferme de l'Ontario était émacié et avait une atrophie séreuse des tissus adipeux. L'autopsie a révélé une atrophie hépatique et une fibrose périportale modérée. Des oeufs et des trématodes observés dans le foie ont été identifiés comme Dicrocoelium dendriticum. Il semblerait qu'il s'agit du premier cas signalé d'infection des équidés par Dicrocoelium dendriticum en Amérique du Nord.(Traduit par Isabelle Vallières).

Immunohistochemical study of hepatic fibropoiesis associated with canine visceral leishmaniasis.

Hepatic fibropoiesis has been confirmed in canine visceral leishmaniasis. In fibrotic disease, hepatic stellate cells (HSC) play an important role in fibropoiesis, undergoing activation by TGF-ß to acquire characteristics of myofibroblasts. These cells show extensive capacity for proliferation, motility, contractility, collagen synthesis and extracellular matrix component synthesis. The aim of this work was to identify markers of HSC activation in 10 symptomatic and 10 asymptomatic dogs naturally infected with Leishmania (Leishmania) infantum. Eight uninfected dogs were used as controls. Alpha-actin (α-SMA), vimentin and cytokeratin were investigated by immunohistochemistry as HSC markers. The cytokine TGF-ß in tissue was also evaluated by immunohistochemistry. All infected dogs showed higher numbers of reticular fibres than controls. Fibropoiesis found in infected dogs was always associated with the presence of parasites and chronic granulomatous hepatitis. Positive correlation was found among fibropoiesis, parasite tissue load and expression of α-SMA. There was no correlation between fibropoiesis, vimentin and cytokeratin markers. The expression of cytokine TGF-ß was higher in infected dogs than in controls, but not significantly different between symptomatic and asymptomatic dogs. These results confirm previous work describing the intense hepatic fibropoiesis in dogs naturally infected with Leishmania infantum, but now associated them with overexpression of TGF-ß, where α-SMA may be a superior marker for activated HSC cells in CVL.

Ductal Plate Malformation in the Liver of Boxer Dogs: Clinical and Histological Features.

Ductal plate malformations (DPMs) represent developmental biliary disorders with a wide phenotypic spectrum. This study characterizes DPM in 30 Boxer dogs. Median age was 1.5 (range, 0.3-10.0) years, with 12 dogs <1 year. Clinical features included increased serum levels of liver enzymes (28), gastrointestinal signs (16), poor body condition (14), abdominal effusion (9), and hepatic encephalopathy (2). Additional malformations included gallbladder atresia (8), atrophied left liver (2), absent quadrate lobe with left-displaced gallbladder (1), portal vasculature atresia (left liver, 1), intrahepatic portosystemic shunt (1), and complex intrahepatic arteriovenous malformation (1). All dogs had portal tracts dimensionally expanded by a moderate-to-severe multiple small bile duct phenotype embedded in abundant extracellular matrix; 80% displayed variable portal-to-portal bridging. Quantitative analysis confirmed significantly increased fibrillar collagen and a 3-fold increased portal tract area relative to 6 Boxer and 10 non-Boxer controls. Biliary phenotype was dominated by tightly formed CK19-positive ductules, typically 10 to 15 µm in diameter, with 3 to >30 profiles per portal tract, reduced luminal apertures, and negative Ki-67 immunoreactivity. CK19-positive biliary epithelium intersected directly with zone 1 hepatocytes as a signature feature when considered with other DPM characteristics. Phenotypic variation included a multiple small bile duct phenotype (all dogs), predominantly thin-walled sacculated ducts (4), well-formed saccular ducts (4), and sacculated segmental, interlobular, and intralobular ducts (Caroli malformation, 2 dogs, one with bridging portal fibrosis). Histologic evidence of portal venous hypoperfusion accompanied increased biliary profiles in every case. We propose that this spectrum of disorders be referred to as DPM with appropriate modifiers to characterize the unique phenotypes.

Serum concentrations of PIIINP aminopeptide in dogs with liver fibrosis.

The aim of the study was to evaluate the serum concentration of the type III procollagen aminopeptide in dogs, and to assess its utility in the diagnosis of liver fibrosis. The study was carried out on 20 dogs of different breeds and of both genders, between 7 and 15 years old. Based on the results of the histopathological examination and the evaluation of the degree of liver fibrosis, the dogs were divided into five groups. The mean serum PIIINP concentration in the group of dogs with stage 1 and 2 liver fibrosis (groups 2 and 3) was five-fold higher than in healthy dogs (group 1). In turn, the mean PIIINP concentration in the group of dogs with stage 3 (group 4) and stage 4 (group 5) fibrosis was 10-fold higher than that of the control group (group 1). Based on the results, we found that the serum PIIINP concentration correlated with the degree of liver fibrosis, assessed based on a histopathological examination. Therefore, PIIINP serum concentration tests may be a promising non-invasive diagnostic technique that could be used in veterinary hepatology to assess the degree of liver fibrosis.

7S Fragment of Type IV Collagen as a Serum Marker of Canine Liver Fibrosis.

The aim of this study was to assess whether the serum levels of the 7S fragment of type IV collagen may aid in diagnosing liver fibrosis in dogs. The study was carried out on 20 dogs with liver disease. Serum levels of the 7S fragment of type IV collagen were measured in all dogs. The analysis showed that healthy dogs and dogs with type 1, 2 and 3 liver fibrosis had low serum concentrations of the 7S fragment of type IV collagen compared to dogs with type 4 liver fibrosis. The study revealed that the assessment of serum levels of the 7S fragment of type IV collagen is useful in the diagnosis of advanced liver fibrosis and cirrhosis.

Hepatic lesions in 90 captive nondomestic felids presented for autopsy.

Hepatic lesions in nondomestic felids are poorly characterized. The purpose of this study was to evaluate hepatic lesions in 90 captive, nondomestic felids including tigers, cougars, and lions. Hepatic lesions were histologically characterized as vacuolar change (lipidosis or glycogenosis), biliary cysts, biliary hyperplasia, hepatitis, necrosis, neoplasia, fibrosis, veno-occlusive disease, cholestasis, hematoma, congestion, or hemorrhage. Stepwise logistic regression analyses were performed for vacuolar change, benign biliary lesions, hepatitis, lipogranulomas, extramedullary hematopoiesis, and hepatic stellate cell hypertrophy and hyperplasia, with species as the outcome variable. Ninety cats met the inclusion criteria. Seventy livers (78%) contained 1 or more lesions. Hepatocellular vacuolar change (41/90 [46%]) was the most common lesion overall. Extramedullary hematopoiesis, lipogranulomas, and hepatic stellate cell hyperplasia were also common. One snow leopard had veno-occlusive disease. Tigers were more likely than other felids to have no significant hepatic histologic lesions (odds ratio [OR], 12.687; P = .002), and lions were more likely to have biliary cysts (OR, 5.97; P = .021). Six animals (7%) died of hepatic disease: cholangiocellular carcinoma (n = 2) and 1 each of hepatic lipidosis, hepatocellular necrosis, pyogranulomatous hepatitis, and suppurative cholecystitis. Hepatocellular iron and copper accumulations were present in 72 of 90 (80%) and 10 of 90 (11%) sections, respectively. Sinusoidal fibrosis was common (74/90 [82%]) and primarily centrilobular (65/74 [88%]). Hepatocellular iron, copper, and fibrosis were not significantly associated with hepatic lesions. Primary hepatic disease was not a common cause of death in nondomestic felids in this study.

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.

Suitability of using serum hialuronic acid concentrations in the diagnosis of canine liver fibrosis.

There are multiple dynamic changes associated with the metabolism of the extracellular matrix (ECM) which occur in the course of liver fibrosis. Therefore, the evaluation of parameters reflecting the deposition of ECM, the activity of myofibroblasts and the synthesis and degradation of collagen may aid in the diagnosis of liver fibrosis. Hyaluronic acid is considered to be a marker of ECM deposition. It is a glycosaminoglycan synthesized by hepatic stellate cells and degraded by hepatic sinusoidal endothelial cells. The aim of this study was to evaluate the concentration of hyaluronic acid in dogs with different degrees of liver fibrosis. The study was carried out on 29 dogs with liver disease. A core needle biopsy of the liver was performed in order to assess the degree of hepatic inflammation. Then, hyaluronic acid serum concentrations were measured. The dogs were divided into five groups based on the histopathological examination and the evaluation of the degree of hepatic fibrosis. The study showed that serum hyaluronic acid concentrations were low in patients with first stage liver fibrosis and in controls, while they were twice as high as control values in the group of dogs with second stage liver fibrosis. These concentrations were three-fold greater than control values in patients with third stage liver fibrosis, and seven-fold greater in patients with liver cirrhosis. Based on the results, it was concluded that serum hyaluronic acid is a useful marker of liver fibrosis and may aid in determining the degree of its advancement.

Intestinal schistosomiasis in chimpanzees on Ngamba Island, Uganda: observations on liver fibrosis, schistosome genetic diversity and praziquantel treatment.

Despite treatment with praziquantel (PZQ) at 40 mg/kg in food, several chimpanzees on Ngamba Island Chimpanzee Sanctuary (NICS) continue to excrete eggs of Schistosoma mansoni. To monitor disease, 8 animals were closely examined under anaesthesia in March 2011 with portable ultrasonography and by rectal snip biopsy. Schistosome genetic diversity had been previously assayed within 4 of these chimpanzees, finding extensive diversity with 27 DNA barcodes encountered, although none was common to all animals. Calcified schistosome eggs were found in the rectal snips from 5 chimpanzees and liver fibrosis was clearly documented, indicative of progressive disease in 6 animals, the latter being surprisingly advanced in a younger chimpanzee. All 8 animals were treated under anaesthesia by oral gavage with PZQ at 60 mg/kg dosing that was well tolerated. These animals were again re-examined in June 2012 using stool and urine sampling. Only 1 chimpanzee appeared to be free from infection and active egg excretion was confirmed in 6 animals. If intestinal schistosomiasis is to be controlled within this setting, a long-term disease management plan is required which should combine active case-detection with an insistent treatment regime with praziquantel for these chimpanzees, exploring perhaps the performance of even higher dosing.

The role of hepatic myofibroblasts in liver cirrhosis in fallow deer (Dama dama) naturally infected with giant liver fluke (Fascioloides magna).

BACKGROUND: This paper describes liver cirrhosis in 35 fallow deer infected with the giant liver fluke, as well as the distribution, origin, and role of myofibroblasts in its development. RESULTS: In liver of infected deer, stripes of connective tissue are wound around groups of degenerated and regenerated liver lobuli. In the connective tissue, lymphocytes and macrophages which often contain parasite hematin are also present. The walls of the bile ducts are thickened, the epithelium multiplied with mucous metaplasia, and desquamated cells, parasite eggs and brown pigment are present in their lumen.In the livers with cirrhosis, immunopositivity to α-SMA and desmin was observed in cells in portal and septal spaces, at the edge between fibrotic septa and the surrounding parenchyma and in perisinusoidal spaces. These cells vary in size, they are round, oval, spindle-shaped or irregular in shape, similar to vascular smooth muscle cells. The derangement of epithelial-mesenchymal interactions detected in chronic cholangiopathies is most probably the pro-fibrogenic mechanism in liver cirrhosis of fallow deer (Dama dama) infected with the giant liver fluke (Fascioloides magna). CONCLUSION: Myofibroblasts, especially hepatic stellate cells (HSCs), play an important role in the synthesis of extracellular matrix components in the development of parasitic fibrosis and cirrhosis in the liver of fallow deer.