[Acute liver failure in a dog after mushroom intake, presumably of the genus Amanita]. / Akutes Leberversagen bei einem Hund nach Aufnahme eines Pilzes, vermutlich der Gattung Amanita.

A 4-year-old, neutered male Husky-mix dog weighing 29.4 kg that reportedly ingested a mushroom most likely of the genus Amanita one day prior to presentation exhibited signs of diarrhea, vomitus, inappetence and progressively worsening lethargy. Clinical chemistry revealed hypoglycemia, hyperbilirubinemia, decreased prothrombin and thromboplastin time, as well as increased liver enzyme activities. Despite hospitalization and supportive therapy over a period of 3 days the dog's general condition worsened leading to euthanasia. The pathomorphological findings were characterized by hemorrhage in several organs, hemorrhagic ingesta, icterus, and marked hepatic cellular necrosis.

Clinical recovery of 5 dogs from amatoxin mushroom poisoning using an adapted Santa Cruz protocol for people.

OBJECTIVE: To describe the clinical course, treatment, and outcome of 5 dogs following ingestion of toxic Amanita spp. mushrooms containing amatoxins using an adapted version of the Santa Cruz protocol developed for people. CASE SERIES SUMMARY: Five dogs were presented with clinical signs compatible with amanitin toxicity with witnessed ingestion noted in 3 of 5 dogs. Clinical findings included acute onset vomiting and diarrhea, lethargy, and hepatopathy including signs of fulminant hepatic failure (increased liver enzyme activities, hyperbilirubinemia, prolonged clotting times, and hypoglycemia were noted among these cases). Urine toxicological screening confirmed the presence of Amanita toxins in 4 cases with expert mycologist speciation in the fifth. Core interventions included percutaneous biliary drainage, use of octreotide, and early nil per os orders. All dogs survived to discharge with this treatment strategy. NEW OR UNIQUE INFORMATION PROVIDED: This case series describes the use of a modified version of the Santa Cruz protocol to address amatoxin-induced fulminant hepatic failure in dogs. The protocol was safe, well tolerated, and all patients made a full clinical recovery.

Deficiency of interleukin-19 exacerbates lipopolysaccharide/D-galactosamine-induced acute liver failure.

Interleukin (IL)-19 is a cytokine clustered in the IL-20 cytokine superfamily with both anti-inflammatory and pro-inflammatory aspects depending on the etiology of inflammatory disease. The function of IL-19 has been evaluated in cutaneous and inflammatory bowel diseases, but has not been studied in liver diseases. Here, we examined the effect of IL-19 on acute liver failure (ALF) using two mouse models of ALF: lipopolysaccharide and D-galactosamine (LPS/GalN)-induced model and concanavalin A (ConA)-induced model. In the LPS/GalN-induced ALF model, which is mainly caused by the innate immune response of liver macrophages, IL-19 knockout (KO) mice showed increased plasma level of liver deviation enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with wild-type (WT) mice. In histopathology of liver sections, IL-19 KO mice exacerbated liver injury with marked hemorrhagic lesions and hepatocellular death in the liver compared with WT mice. In this model, mRNA expressions of pro-inflammatory chemokines, CCL2 and CCL5 were increased in liver tissue from IL-19 KO mice compared with WT mice. Moreover, the mRNA expressions of IL-19 and its receptor subunit were induced in liver tissue by LPS/GalN administration. However, there is no difference in liver injury between WT and IL-19KO in the ConA-induced ALF model induced by CD4+ T cell activation. These data suggest that IL-19 has a protective effect against inflammation-mediated liver injury, which is dependent on the etiology.

Mucosal expression of defensin-5, soluble phospholipase A2 and lysozyme in the intestine in a rat model of acute liver failure and its relationship to intestinal bacterial translocation / Expresión de defensina-5, fosfolipasa A2 soluble y lisozima en la mucosa intestinal en un modelo de rata con insuficiencia hepática aguda y su relación con la traslocación bacteriana intestinal

INTRODUCTION: To study the expression of defensin-5 (RD-5), soluble phospholipase A2 (sPLA2) and lysozyme in the intestine in a rat model of acute liver failure and its relationship with intestinal bacterial translocation (BT). PATIENTS AND METHODS: Sprague-Dawley (SD) rats were divided into two groups. The experimental group was divided into five subgroups according to the lapsing time after the model was established, which were designated accordingly as 8 h, 16 h, 24 h, 48 h, and 72 h groups. Acute liver failure (ALF) model was induced by intraperitoneal injection of 10% d-galactosamine. The homogenates of mesenteric lymph nodes (MLNs), liver and spleen from each group were cultured in agar to determine the bacterial outgrowth. The mRNA expression of RD-5, sPLA2, lysozyme and the protein expression of sPLA2, lysozyme were determined. RESULTS: No bacteria grew in the organ cultures from the control group while experimental groups had positive cultures. Expression of the RD-5 and sPLA2 mRNA in the experimental groups gradually increased at early time points and peaked 16 h after induction of ALF, then progressively decreased. The mRNA expression of lysozyme in the experimental group peaked at 8 h after ALF induction, then progressively decreased. Similar results were obtained with Western blot and immunohistochemical staining. DISCUSSION: The immune barrier function of the ileal mucosa in the rat model of acute liver failure was compromised as demonstrated by the decreased expression of RD-5, sPLA2 and lysozyme in Paneth cells along with increased intestinal bacterial translocation

INTRODUCCIÓN: Estudiar la expresión de defensina-5 (RD-5), fosfolipasa A2 soluble (sPLA2) y lisozima en el intestino de un modelo de rata con insuficiencia hepática aguda y su relación con la traslocación bacteriana (TB) intestinal. PACIENTES Y MÉTODOS: Se dividieron ratas Sprague-Dawley® (SD) en 2 grupos. El grupo experimental se dividió en 5 subgrupos según el tiempo transcurrido desde que se estableció el modelo, y se designaron en consecuencia como grupos de 8, 16, 24, 48 y 72 h. El modelo de insuficiencia hepática aguda (IHA) se indujo mediante inyección intraperitoneal de D-galactosamina al 10%. Se cultivaron homogeneizados de ganglios linfáticos mesentéricos (GLM), hígado y bazo de cada grupo en agar para determinar la proliferación bacteriana. Se determinaron la expresión de ARNm de RD-5, sPLA2 y lisozima, y la expresión de proteínas de sPLA2 y lisozima. RESULTADOS: En los cultivos de órganos del grupo de control no creció ninguna bacteria, mientras que los grupos experimentales presentaron cultivos positivos. La expresión del ARNm de RD-5 y sPLA2 en los grupos experimentales aumentó gradualmente en los primeros momentos y alcanzó el máximo 16 h después de la inducción de la IHA, para después disminuir de forma progresiva. La expresión de lisozima en el grupo experimental alcanzó el valor máximo 8 h después de la inducción de la IHA y después disminuyó progresivamente. Se obtuvieron resultados similares con la inmunoelectrotransferencia y la tinción inmunohistoquímica. DISCUSIÓN: La función de barrera inmunológica de la mucosa ileal en el modelo de rata de insuficiencia hepática aguda se vio afectada, como lo demuestra la disminución de la expresión de RD-5, sPLA2 y lisozima en las células de Paneth junto con el aumento de la translocación bacteriana intestinal

Clinical and histologic outcome in a dog surviving massive hepatic necrosis.

This report describes the clinical and histologic recovery of a 2-year-old mixed-breed dog presented with hypovolemic shock, markedly increased serum alanine amino transferase activity, and hemoabdomen. Emergency exploratory surgery revealed a friable liver with multiple capsule hemorrhages necessitating removal of the left lateral lobe. Histologic evaluation showed acute massive hepatic necrosis with centrilobular and midzonal distribution. The dog survived, and all monitored laboratory values normalized within 7 weeks. A liver biopsy taken 8 weeks after presentation revealed normal hepatic architecture with a few, randomly distributed neutrophilic foci. Follow-up included intermittent determination of liver variables including liver function tests for a period of 7 years. The dog's health status, and all test results remained normal during this time. Complete recovery and good long-term quality of life after life-threatening acute liver failure secondary to massive hepatic necrosis is possible in dogs.

Acute liver failure in two dogs following ingestion of cheese tree (Glochidion ferdinandi) roots.

OBJECTIVE: To describe the management and resolution of acute liver failure (ALF) in two dogs following ingestion of cheese tree (Glochidion ferdinandi) roots. CASE SUMMARIES: A 2-year-old male entire Bullmastiff and a 5-year-old female neutered German Shepherd dog were presented for acute-onset lethargy and vomiting after chewing on tree roots of a cheese tree. Both dogs developed clinical abnormalities consistent with ALF, including hepatic encephalopathy, marked increase in alanine aminotransferase activity and bilirubin concentration, and prolonged coagulation times. Treatment included administration of intravenous fluids, hepatoprotectants, vitamin K1 , antibiotics, lactulose, antacids, antiemetics, and multiple fresh frozen plasma transfusions. Follow-up examinations performed 30 days after initial presentation revealed the dogs to be clinically healthy with serum biochemical and coagulation profiles within reference intervals. NEW OR UNIQUE INFORMATION: This is the first report describing ALF in two dogs following ingestion of cheese tree (G. ferdinandi) roots. In this clinical setting, despite a poor prognosis, survival and recovery of adequate liver function were possible with medical management.

Xylitol Toxicosis in Dogs: An Update.

Xylitol ingestions in dogs may result in severe hypoglycemia followed by acute hepatic failure and associated coagulopathies. Aggressive treatment may be needed, but the prognosis is generally expected to be good for dogs developing uncomplicated hypoglycemia. Because of increased availability of xylitol-containing products in the market and in the dog's environment, it is likely that there will continue to be increased exposures and toxicity in dogs.

Acute Liver Injury and Failure.

Acute liver injury and acute liver failure are syndromes characterized by a rapid loss of functional hepatocytes in a patient with no evidence of pre-existing liver disease. A variety of inciting causes have been identified, including toxic, infectious, neoplastic, and drug-induced causes. This article reviews the pathophysiology and clinical approach to the acute liver injury/acute liver failure patient, with a particular emphasis on the diagnostic evaluation and care in the acute setting.

Retrospective evaluation of acute liver failure in dogs (1995-2012): 49 cases.

OBJECTIVE: To characterize the clinical presentation and outcome of dogs with acute liver failure (ALF). DESIGN: Retrospective case series from January 1995 to December 2012. SETTING: University teaching hospital. ANIMALS: Forty-nine dogs were diagnosed with ALF defined as the acute onset of clinical signs accompanied by serum hyperbilirubinemia and coagulopathy (prothrombin time >1.5 times the upper limit of the reference interval) with or without signs of hepatic encephalopathy. METHODS: Medical records were retrospectively analyzed for clinical presentation, history, physical examination findings, clinicopathologic data, diagnostic imaging findings, hepatic histopathology, treatment, and outcome. MAIN RESULTS: Presenting signs included anorexia (28/49, 57%), vomiting (25/49, 51%), neurologic abnormalities (17/49, 35%), and polydipsia/polyuria (10/49, 20%). Neurologic impairment compatible with hepatic encephalopathy occurred at some point during hospitalization in 28/49 (57%) of dogs. Common clinicopathologic abnormalities on presentation other than hyperbilirubinemia and increased serum liver enzyme activity included thrombocytopenia (25/49, 51%), hypoalbuminemia (23/49, 46%), leukocytosis (17/49, 34%), anemia (14/49, 29%), hypokalemia (13/49, 27%), and hypoglycemia (10/49, 20%). The causes of ALF included neoplasia (13/49, 27%), presumptive leptosporosis (4/49, 8%), and ischemia (1/49, 2%). The remaining cases were idiopathic although 15 of these dogs had exposure to possible hepatotoxins. Common lesions in the 35/49 (71%) dogs that had hepatic histopathology were necrosis (19/39, 48%), lipidosis (16/39, 41%), vacuolar change (7/49, 14%), and inflammation (4/49, 8%). Complications included ascites (20/49, 41%), bleeding tendencies (14/49, 29%), pancreatitis (12/49, 24%), and acute tubular necrosis (11/49, 22%). Seven (14%) dogs survived to discharge. Survivors had higher alanine aminotransferase activity, and were more likely to maintain normal albumin concentrations and not develop clinical bleeding or ascites during hospitalization. CONCLUSIONS: Canine ALF is associated with multiple etiologies and a high mortality rate. Strategies to increase survival are urgently required.

Acute Hepatic Failure in a Dog after Xylitol Ingestion.

Xylitol is a five-carbon sugar alcohol produced from natural resources frequently used as a sugar substitute for humans. We report the development and successful treatment of acute hepatic failure and coagulopathy in a dog after xylitol ingestion. A 9-year-old 4.95 kg (10.9 lb) neutered male Chihuahua was evaluated at a veterinary clinic for vomiting after ingesting 224 g (45 g/kg, 20.5 g/lb) of granulated xylitol. Hypoglycemia developed within 1-2 h, elevated liver values, suggesting the development of acute hepatic failure, within 12 h and coagulopathy less than 24 h after ingestion. Treatment included maropitant, intravenous dextrose, phytonadione, metronidazole, and fresh frozen plasma. N-acetylcysteine (NAC) and S-adensoyl-L-methionine (SAMe) provided hepatic detoxification and support. The dog survived and liver values returned to normal within 1 month post ingestion. No adverse effects to hepatic function have been identified 2 years after acute xylitol toxicity. This paper is one of the few reports of successful management of a dog with hypoglycemia, hepatic failure, and coagulopathy caused by xylitol toxicity. To date, this is the highest published xylitol dose survived by a dog, as well as the only reported case that documents laboratory changes throughout the course of toxicity and includes normal hepatic indices for 7 months following xylitol toxicity. The rapidly expanding use of xylitol in a variety of products intended for human consumption has led to a rise in xylitol toxicity cases reported in dogs, and clinicians should be aware that more dogs may potentially be exposed and develop similar manifestations.

Thromboelastographic Evaluation of Dogs with Acute Liver Disease.

BACKGROUND: Given the liver's pivotal role in hemostasis and fibrinolysis, the coagulopathy accompanying hepatic disease is complex. HYPOTHESIS/OBJECTIVES: To prospectively evaluate kaolin-activated thromboelastography (TEG) in dogs with acute liver disease (ALD) and compare with plasma-based coagulation tests. ANIMALS: Twenty-one dogs with a diagnosis of ALD based on recent onset of clinical signs accompanied by increases in serum bilirubin concentration and alanine aminotransferase activity. METHODS: Clinical presentation, CBC, serum biochemistry, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and TEG analysis were evaluated in 21 dogs with a subset also having fibrinogen, antithrombin (AT) activity, protein C (PC) activity, d-dimers, and von Willebrand's factor (vWF) activity analyzed. A PT >1.5 times the upper limit of normal defined acute liver failure (ALF). RESULTS: Dogs with ALD had mean increases in R, K, LY30, PT, aPTT, and vWF activity, and decreases in angle, maximal amplitude (MA), G, AT activity, and PC activity. The TEG results defined dogs as hypocoagulable (11/21), normocoagulable (8/21), or hypercoagulable (2/21). Increases in LY30 defined 8/21 dogs as hyperfibrinolytic. Hypocoagulable and hyperfibrinolytic dogs had lower fibrinogen and PC activity than dogs without these abnormalities. Overall, ALF dogs had greater increases in K and LY30, and decreases in MA, G, and PC activity than dogs with less severe hepatic impairment. Results for MA and LY30 were positively correlated with serum bilirubin concentration and white blood cell count, and negatively correlated with serum cholesterol concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: ALD dogs have a range of coagulation abnormalities that trend toward hypocoagulability and hyperfibrinolysis as functional impairment occurs.

Acute liver failure in dogs and cats.

OBJECTIVE: To define acute liver failure (ALF), review the human and veterinary literature, and discuss the etiologies and current concepts in diagnostic and treatment options for ALF in veterinary and human medicine. ETIOLOGY: In veterinary medicine ALF is most commonly caused by hepatotoxin exposure, infectious agents, inflammatory diseases, trauma, and hypoxic injury. DIAGNOSIS: A patient may be deemed to be in ALF when there is a progression of acute liver injury with no known previous hepatic disease, the development of hepatic encephalopathy of any grade that occurs within 8 weeks after the onset of hyperbilirubinemia (defined as plasma bilirubin >50 µM/L [>2.9 mg/dL]), and the presence of a coagulopathy. Diagnostic testing to more specifically characterize liver dysfunction or pathology is usually required. THERAPY: Supportive care to aid the failing liver and compensate for the lost functions of the liver remains the cornerstone of care of patients with ALF. Advanced therapeutic options such as extracorporeal liver assist devices and transplantation are currently available in human medicine. PROGNOSIS: The prognosis for ALF depends upon the etiology, the degree of liver damage, and the response to therapy. In veterinary medicine, the prognosis is generally poor.

Pathologic findings and toxin identification in cyanobacterial (Nodularia spumigena) intoxication in a dog.

A 3-year-old Cairn Terrier dog that had been in contact with sea water containing cyanobacteria (blue-green algae) was euthanized because of acute hepatic failure and anuria after a 5-day illness. Histologic findings included lytic and hemorrhagic centrilobular hepatocellular necrosis and renal tubular necrosis. The cyanotoxin nodularin was detected in liver and kidney by high-performance liquid chromatography-mass spectrometry. Nodularin is a potent hepatotoxin produced by the algal species Nodularia spumigena. The intensity of algal blooms has increased during the past decades in the Baltic Sea region, thus increasing the risk for intoxications in domestic and wild animals. The authors describe the pathologic findings of cyanobacterial toxicosis in a dog with direct identification of the toxin from organ samples.

Hepatic dysfunction.

This article reviews the common pathophysiology that constitutes hepatic dysfunction, regardless of the inciting cause. The systemic consequences of liver failure and the impact of this condition on other organ systems are highlighted. The diagnostic tests available for determining the cause and extent of liver dysfunction are outlined, treatment strategies aimed at supporting hepatic health and recovery are discussed, and prognosis is briefly covered. The article emphasizes the fact that because of the central role of the liver in maintaining normal systemic homeostasis, hepatic dysfunction cannot be effectively addressed as an isolated entity.

Signaling pathways involved in liver injury and regeneration in rabbit hemorrhagic disease, an animal model of virally-induced fulminant hepatic failure.

Management of fulminant hepatic failure (FHF) continues to be one challenging problem, and experimental animal models resembling its clinical conditions are still needed. Rabbit hemorrhagic disease (RHD) fullfils many requirements of an animal model of FHF. This work investigated changes in MAPK, NF-kappaB, AP-1 and STAT pathways during RHD-induced liver injury. Rabbits were infected with 2 x 10(4) hemagglutination units of an RHD virus isolate. Apoptosis was documented by the presence of caspase-3 activity and substantial PARP proteolysis at 36 and 48 h postinfection (pi). Infection induced a marked and maintained expression of TNF-alpha from 12 h pi, while there was only a transitory increase in IL-6 expression. Expression of phosphorylated (p)-JNK, p-p38 and p-ERK1/2 was significantly elevated at 12 h pi. At 48 h pi p-JNK expression was maintained at a maximum level, while that of p-p38 returned to normality and there was no p-ERK1/2 expression. Activation of NF-kappaB and AP-1 and increased expression of VCAM-1 and COX-2 were observed. No significant changes were detected in activation of STAT1 and STAT3, while SOCS3 expression increased significantly. The current findings suggest that activation of JNK is an essential component in liver injury mediated by the RHD virus and that lack of activation of STAT3, probably mediated by SOCS3 over-expression, would contribute to the inhibition of the regenerative response. Data show the presence of molecular mechanisms contributing to liver damage and the lack of regeneration and they support the usefulness of this model to investigate novel therapeutical modalities in FHF.

Fatal fulminant hepatitis in a chimpanzee (Pan troglodytes) receiving cyproterone acetate.

Cyproterone acetate is a steroidal anti-androgen that has been used in human medicine for contraceptive purposes as well as treatment of medical conditions responsive to suppression of testosterone production. While serious side effects are considered to be rare, sporadic cases of severe hepatitis have been reported, including several fatal cases. This report describes a case of fatal fulminant hepatitis in one of four male chimpanzees (Pan troglodytes) that were undergoing trial treatment with cyproterone acetate to decrease inter-male aggression.

Spotted black snake (Pseudechis guttatus) envenomation in a maned wolf (Chrysocyon brachyurus).

Envenomation by a spotted black snake (Pseudechis guttatus), following multiple bites on the buccal mucosa of a captive maned wolf (Chrysocyon brachyurus), caused the animal's collapse, hemolysis, rhabdomyolysis, local tissue necrosis, hepatic and renal failure, and subsequent death. The wolf died despite intensive supportive care including antivenom administration, fluid support, and a blood transfusion. Gross necropsy findings included myocardial and intestinal hemorrhage, pulmonary congestion, hepatomegaly, and splenomegaly. Microscopic examination of formalin-fixed tissues demonstrated pulmonary and abdominal visceral hemorrhage, acute nephrosis with casts, multifocal hepatic necrosis, and splenic congestion.