Ataxia and weakness as uncommon primary manifestations of hepatic encephalopathy in a 15‐year‐old trotter gelding

A 15‐year‐old trotter gelding was evaluated because of an acute onset of ataxia in all 4 limbs. There was no known history of trauma. The gelding showed grade 2/5 ataxia in all 4 limbs, which was localised after clinical neurological examination to the cervical vertebral spinal cord. Initial therapy consisted of oral anti‐inflammatory doses of prednisolone and antimicrobial treatment with potentiated sulphonamides. The ataxia progressed to grade 3/5 at Day 10 of hospitalisation. Additionally, the horse was slightly depressed and showed spontaneous yawning during examination. Facial sensation was blunted. Blood chemistry revealed a marked elevation of liver specific enzymes and blood ammonia levels. Transcutaneous abdominal ultrasonography revealed hepatomegaly. Due to a guarded prognosis, the horse was subjected to euthanasia. At necropsy the left lateral liver lobe was markedly enlarged and showed a firm texture, whereas the cranial part and the right and quadratic liver lobe displayed a severe and diffuse atrophy. Histopathologically, the left lateral liver lobe revealed a moderate to severe cirrhosis with a severe, diffuse hepatocellular iron‐accumulation. Increased numbers of Alzheimer type II astrocytes in the cerebral cortex and cerebral white matter vacuolisation were indicative for encephalopathy. These findings were interpreted as haemosiderosis and cirrhosis of the liver with consecutive hepatic encephalopathy. Aetiologically, haemosiderosis should be considered as a cause of liver cirrhosis with consecutive hepatic encephalopathy. Although hepatic encephalopathy in horses usually presents with predominating cerebral signs, it has to be taken into account as a differential diagnosis in cases of acute onset generalised ataxia.     

A systematic review and meta‐analysis of predictors of human hepatitis E virus exposure in non‐endemic countries

The reported incidence of clinical hepatitis E cases is rising in some non‐endemic countries, with concurrent concerns regarding potential hepatitis E virus (HEV) contamination of the blood supply. Therefore, the characterization of major potential sources of human HEV exposure is important to inform risk assessment and public health policy. A systematic review was conducted, including a comprehensive search in six electronic bibliographic databases, verified by hand‐searching reference lists of HEV reviews, and a grey literature search, of the broad research question ‘what is the evidence of the association between predictors of human HEV exposure, and HEV IgG seropositivity, in non‐endemic countries?’ Using forms designed a priori, captured studies were appraised at first‐level screening, second‐level characterization, and third‐level data extraction and risk of bias assessment. Meta‐analysis yielded summary estimates of association between potential predictors and odds of HEV seropositivity. Meta‐analysis and meta‐regression of the odds of HEV seroprevalence in specific groups characterized potential sources of HEV exposure. From 4,163 captured citations, 245 relevant studies underwent data extraction, investigating HEV seroprevalence or predictors in both healthy subjects and targeted patient groups. Across these groups, increasing age was a predictor of HEV IgG seropositivity. Both human immunodeficiency virus patients and haemodialysis patients had significantly increased odds of HEV seropositivity relative to the general population. Working with pigs, in forestry, or in hospitals, was significantly associated with increased odds of HEV seropositivity, as were consumption of meat, pork or game meat, or hunting. Chronological time was not associated with HEV seropositivity within our data sets. Further study of the distribution of potential dietary or behavioural predictors between high and lower prevalence areas within non‐endemic countries could improve our understanding of the relative importance of specific HEV transmission pathways.     

Theiler's disease associated with administration of tetanus antitoxin contaminated with nonprimate (equine) hepacivirus and equine parvovirus-hepatitis virus

An 11-year-old Trakehner gelding was presented for evaluation of lethargy, decreased appetite, mild icterus, and elevated hepatic enzyme activities. Physical examination, serum chemistry results, and liver biopsy histopathologic findings were supportive of Theiler's disease. Polymerase chain reaction (PCR) testing results of serum and liver tissue were positive for nonprimate (equine) hepacivirus (NPHV) and a novel equine parvovirus-hepatitis virus (EqPV-H). PCR testing of the lot of tetanus antitoxin administered to the gelding 3 months previously also yielded positive results for NPHV and EqPV-H. Treatment included supportive care and clinical signs resolved within 1 week, although hepatic enzyme activities remained elevated for several months. The horse successfully returned to work as a hunter/jumper for about 1 year until it developed a forelimb lameness and progressive atrophy of shoulder musculature (sweeney), prompting a decision for euthanasia 20 months after initial evaluation. Serial PCR testing of serum revealed persistent infection with both NPHV and EqPV-H and necropsy examination revealed chronic active hepatitis, mild liver atrophy, and positive PCR results for NPHV and EqPV-H in liver tissue. This case highlights the possible risk of administering potentially contaminated biologics of equine origin and the importance of screening for recently identified hepatic viruses in donors from which blood products are prepared.     

IMAGING DIAGNOSIS—TRANSCRANIAL COLOR‐CODED DUPLEX SONOGRAPHY IN A DOG WITH HEPATIC ENCEPHALOPATHY

We report the use of transcranial Doppler ultrasonography in a dog with hepatic encephalopathy secondary to a congenital portosystemic shunt. A severe increase in the pulsatility index was measured in the right middle cerebral artery, left middle cerebral artery, and basilar artery. These values returned to normal following medical stabilization of the patient and resolution of the neurologic signs. Transcranial Doppler ultrasonography appears to have value for monitoring the status of intracranial hypertension in patients with hepatic encephalopathy.     

Capsosiphon fulvescens extracts improve obesity‐associated metabolic disorders and hepatic steatosis in high‐fat diet‐induced obese mice

Herbal dietary supplements have attracted more and more attention owing to their relative effectiveness in obesity ‐related metabolic disorders and diseases. This study investigated the therapeutic effects and underlying mechanisms of Capsosiphon fulvescens (CF) extracts on obesity, their associated metabolic disorders and hepatic steatosis in high‐fat diet (HFD)‐induced obese mice. Male C57BL/6 mice were fed with normal, HFD/Vehicle and HFD/CF (orally 300 mg/kg/day for CF). After 12 weeks, CF blocked HFD‐induced body weight, food intake, liver weight, hepatic triglyceride (TG), fat mass (weight of abdominal subcutaneous fat and epididymal adipose tissue) and biochemical parameters (total cohlesterol, glucose, TG, creatinine, high‐density lipoproteins cholesterol and low‐density lipoprotein cholesterol) of serum. CF also had improved serum levels of adiponectin, leptin and insulin‐like growth factor‐1 in HFD/CF mice. Moreover, CF ameliorated the hepatic steatosis‐reducing size of white adipose tissue. These results indicate that CF have anti‐obesity effects and are effective for reducing metabolic risk and hepatic steatosis.     

The effects of nutrition‐induced abnormal food metabolism in the Southern Plains woodrat (Neotoma micropus): comparisons of variations of the Western diet

We investigated the effects of several modifications of the Western diet on a medium‐sized rodent, Neotoma micropus, that lives in the area of the wildland‐urban interface. We conducted a laboratory study of the response of N. micropus to high fat‐high fructose (HFHF), high fat‐high sucrose (HFHS), high fat‐low sugar (HFLSu) and control (low fat‐low sugar) diets. We found a significant increase in hepatic lipid deposition and a significant decrease in podocytes in those animals that consumed the HFHF and HFLSu diets compared to those on the HFHS and control diets. We found no significant differences in Bowman's space or hepatic collagen formation. We predict that N. micropus in the wild, with access to anthropogenic resources, will show similar effects as a result of the consumption of anthropogenic resources.     

Branched‐chain amino acid ratios in low‐protein diets regulate the free amino acid profile and the expression of hepatic fatty acid metabolism‐related genes in growing pigs

Liver metabolism is affected by nutrients. The aim of this study was to explore the effects of low‐protein diets (17% crude protein, CP) supplemented with branched‐chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile) and valine (Val), on hepatic amino acid profile and lipid metabolism in growing pigs. The ratio of Leu : Ile : Val in all groups was 1 : 0.51 : 0.63 (20% crude protein, CP), 1 : 1 : 1 (17% CP), 1 : 0.75 : 0.75 (17% CP), 1 : 0.51 : 0.63 (17% CP) and 1 : 0.25 : 0.25 (17% CP) respectively. Results revealed that compared to the positive control group (1 : 0.51 : 0.63, 20% CP), the low‐protein diets significantly augmented the concentrations of most essential amino acids and non‐essential amino acids (p < .05), with the greatest values observed in the 1 : 0.25 : 0.25 group. Moreover, relative to the control, the low‐protein diets with the Leu : Ile : Val ratio ranging from 1 : 0.75 : 0.75 to 1 : 0.25 : 0.25 markedly downregulated the mRNA abundance of acetyl‐CoA carboxylase (ACC), lipoprotein lipase (LPL) and fatty acid‐binding protein 4 (FABP‐4) (p < .05), and upregulated the mRNA expression of hormone‐sensitive lipase (HSL), peroxisome proliferator‐activated receptor‐g coactivator‐1α (PGC‐1α), uncoupling protein 3 (UCP3) and liver carnitine palmitoyltransferase 1 (L‐CPT‐1) (p < .05). Therefore, our data suggest that protein‐restricted diets supplemented with optimal BCAA ratio, that is, 1 : 0.75 : 0.75–1 : 0.25 : 0.25, induce a shift from fatty acid synthesis to fatty acid oxidation in the liver of growing pigs. These effects may be associated with increased mitochondrial biogenesis.     

TRIPLE‐PHASE HELICAL COMPUTED TOMOGRAPHY IN DOGS WITH HEPATIC MASSES

The purpose of this study was to determine the utility of triple‐phase helical computed tomography (CT) for differentiating canine hepatic masses. Seventy dogs with hepatic masses underwent triple‐phase CT followed by surgical removal of the hepatic masses. Triple‐phase helical CT scans for each dog included precontrast, arterial phase, portal venous phase, and delayed phase studies. The removed hepatic masses were histopathologically classified as hepatocellular carcinoma (n = 47), nodular hyperplasia (n = 14), and hepatic metastatic tumors (n = 9) in dogs. Of the 47 hepatocellular carcinomas, the most common CT findings included a heterogeneous pattern with hyper‐, iso‐, and hypoenhancement in both the arterial and portal venous phases (40/47, 85.1%). Of the 14 nodular hyperplasias, the most common CT findings were a homogeneous pattern with hyper‐ and isoenhancement in both the portal venous and delayed phases (13/14, 92.9%). Of nine hepatic metastatic tumors, the most common CT findings included a homogeneous hypoenhancement pattern in both the arterial and portal venous phases (8/9, 88.9%). In addition, 5 (55.6%) showed homogeneous hypoenhancement patterns in the delayed phase. Findings from our study indicated that triple‐phase CT is a useful tool for preoperative differentiation of hepatocellular carcinoma, nodular hyperplasia, and hepatic metastatic tumors in dogs.     

Plasma L-carnitine concentration in healthy dogs and dogs with hepatopathy

BACKGROUND: L-Carnitine has an essential role in lipid metabolism. Disturbances of L-carnitine metabolism can influence the energy supply of the organism. L-Carnitine is synthesized exclusively in the liver. Hence, we hypothesized that liver disease can influence L-carnitine metabolism. OBJECTIVES: The goal of this study was to compare plasma L-carnitine concentrations in dogs with different liver diseases of differing severity with the plasma L-carnitine concentrations of healthy dogs. METHODS: Sixteen dogs with inflammatory liver disease and 12 dogs with liver neoplasia were included in the study. Liver disease was diagnosed by clinical chemistry, ultrasonography, and histology of liver biopsy specimens. L-Carnitine concentration was measured in plasma samples using mass spectrometry, and compared among groups using unpaired Student's t-tests. RESULTS: Compared with healthy controls (24.4 +/- 8.4 micromol/L), the plasma L-carnitine concentration in dogs with liver disease (44.2 +/- 23.7 micromol/L) was significantly higher (P<.0001). The difference in L-carnitine concentration between dogs with moderate (n=8; 33.6 +/- 13.7 micromol/L) and severe (n=8; 57.4 +/- 22.9 micromol/L) hepatitis was also significant (P=.02). No difference in plasma L-carnitine concentration was found between dogs with hepatitis and those with liver tumors. CONCLUSIONS: Liver disease in dogs was accompanied by elevated plasma L-carnitine concentration. The severity of hepatitis appears to influence L-carnitine concentration.     

Evaluation of β‐carotene assimilation in leopard geckos (Eublepharis macularius)

Although leopard geckos (Eublepharis macularius) are commonly kept under human care, their vitamin requirements are largely unknown. Many invertebrate preys display a low vitamin A concentration; thus, gut‐loading insects with vitamin A or carotenoids is a common practice. The objective of this prospective experimental study was to investigate whether dietary supplementation with β‐carotene, including prey gut‐loading, leads to sufficient vitamin A hepatic storage and prevents epithelial squamous metaplasia development in leopard geckos. Ten clinically healthy female leopard geckos were randomly divided in two groups with various supplementations: a group receiving vitamin A supplementation and a group receiving β‐carotene. Insects were gut‐loaded continuously with a supplement containing vitamin A or β‐carotene, depending on the group. Oral supplementation with cod liver oil or carrot juice was administered weekly to each lizard from “vitamin A group” and “carotenoid group” respectively. After 10 weeks of supplementation, surgical hepatic biopsies were obtained in three geckos of each group while the two remaining geckos were euthanized to undergo complete necropsy. Hepatic vitamin A concentration was determined for each lizard (n = 10) by ultra‐performance liquid chromatography. Histopathology revealed hepatocellular vacuolization and vitellogenic follicles in five females. Epithelial squamous metaplasia was not observed in any of the geckos. Hepatic vitamin A concentration was significantly higher in the carotenoid‐supplemented group than in the vitamin A‐supplemented group (p = 0.03). Our results suggest that in leopard geckos, dietary supplementation with β‐carotene allows sufficient vitamin A hepatic storage.     

X‐RAY ATTENUATION OF THE LIVER AND KIDNEY IN CATS CONSIDERED AT VARYING RISK OF HEPATIC LIPIDOSIS

X‐ray attenuation of the liver has been measured using computed tomography (CT) and reported to decrease in cats with experimentally induced hepatic lipidosis. To assess the clinical utility of this technique, medical records and noncontrast CT scans of a series of cats were retrospectively reviewed. A total of 112 cats met inclusion criteria and were stratified into three hepatic lipidosis risk groups. Group 1 cats were considered low‐risk based on no history of inappetence or weight loss, and normal serum chemistry values; Group 2 cats were considered intermediate risk based on weight loss, serum hepatic enzymes above normal limits, or reasonably controlled diabetes mellitus; and Group 3 cats were considered high risk based on poorly controlled diabetes mellitus due to hypersomatotropism. Mean CT attenuation values (Hounsfield units, HU) were measured using regions of interest placed within the liver and cranial pole of the right kidney. Hepatic and renal attenuation were weakly positively correlated with each other (r = 0.2, P = 0.03) and weakly negatively correlated with body weight (r = ?0.21, P = 0.05, and r = ?0.34, P = 0.001, respectively). Mean (SD) hepatic and renal cortical attenuation values were 70.7 (8.7) HU and 49.6 (9.2) HU for Group 1 cats, 71.4 (7.9) HU and 48.6 (9.1) HU for Group 2, and 68.9 (7.6) HU and 47.6 (7.2) HU for Group 3. There were no significant differences in hepatic or renal attenuation among groups. Findings indicated that CT measures of X‐ray attenuation in the liver and kidney may not be accurate predictors of naturally occurring hepatic lipidosis in cats.     

LPS-TLR4/MD-2–TNF-α signaling mediates alcohol-induced liver fibrosis in rats

Liver fibrosis results from liver inflammation and progresses to liver cirrhosis or liver cancer. It is known that nonalcoholic liver disease is mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2)–tumor necrosis factor-alpha (TNF-α) signaling pathway. This study aimed to investigate whether alcoholic liver disease is also mediated by this pathway. To this end, we first established rat models of liver fibrosis by administering alcohol. Next, the rats were injected with anti-TLR4 and anti-MD-2 antibodies. Real Time Quantitative PCR (RT-qPCR) and Western blotting were used to detect the activation of the TLR4/MD-2–TNF-α signaling pathway and hepatic stellate cells (HSCs). Moreover, the expression of molecules related to liver fibrosis was estimated. The morphology of rat liver tissue was observed through hematoxylin–eosin staining and Masson staining. For in vitro studies, Kupffer cells (KCs) isolated from the liver were transfected with si-TLR4 and si-MD-2 and co-cultured with HSCs to determine the activity of HSCs. It was found that alcohol treatment activated the TLR4/MD-2–TNF-α signaling pathway and upregulated the molecules associated with liver fibrosis. However, inhibition of TLR4 and MD-2 partially reversed this trend. Notably, in vitro studies indicated that knockdown of TLR4 and MD-2 in KCs partially inhibited LPS-induced activation of KCs and HSCs. Overall, this study showed that alcohol induces liver fibrosis via the LPS-TLR4/MD-2–TNF-α signaling pathway.     

ASSOCIATIONS BETWEEN DUAL‐PHASE COMPUTED TOMOGRAPHY FEATURES AND HISTOPATHOLOGIC DIAGNOSES IN 52 DOGS WITH HEPATIC OR SPLENIC MASSES

Ability to noninvasively differentiate malignant from nonmalignant abdominal masses would aid clinical decision making. The aim of this retrospective, cross‐sectional study was to identify features in dual‐phase computed tomographic (CT) studies that could be used to distinguish malignant from nonmalignant hepatic and splenic masses in dogs. Medical records were searched for dogs that had an abdominal dual‐phase CT examination, a hepatic or splenic mass, and subsequent histopathologic diagnosis. Computed tomographic images for all included dogs were acquired prior to and <30 s (early phase) and >60 s (delayed phase) after intravenous contrast administration. Fifty‐two dogs with 55 masses were studied: 24 hepatic, including 14 (58%) malignant and 10 (42%) non‐malignant; 31 splenic, including 18 (58%) malignant and 13 (42%) nonmalignant. There was substantial overlap in the pre‐ and postcontrast CT features of malignant and nonmalignant hepatic and splenic masses. Regardless of histologic diagnosis, hepatic masses most frequently showed marked, generalized enhancement in early phase images that persisted in the delayed phase. Splenic hemangiosarcoma and nodular hyperplastic lesions most frequently showed marked, generalized enhancement in early phase images that persisted in delayed images whereas most splenic hematomas had slight enhancement in early phase images. All splenic hematomas and 77% of the hemangiosarcomas had contrast accumulation compatible with active hemorrhage. There were no other significant differences in quantitative or categorical CT data between malignant and nonmalignant hepatic or splenic masses. Dual‐phase CT of dogs with hepatic or splenic masses provides limited specific diagnostic information.     

Clove bud (Syzygium aromaticum) improved blood and hepatic antioxidant indices in laying hens receiving low n‐6 to n‐3 ratios

This study was carried out to investigate the effects of different levels of clove bud (Syzygium aromaticum) powder and vitamin E on serum lipid profile, enzyme activities and antioxidant indices, as well as hepatic biochemical and histological alterations in laying hens receiving different n‐6 to n‐3 ratios. A total of 160 laying hens, 43 weeks of age, were allotted to 8 experimental diets with 5 cages of 4 birds each. Dietary treatments consisted of two ratios of n‐6 to n‐3 (16.71 and 2.35), three levels of clove bud (0.0, 2.0 and 4.0 g/kg) and a high vitamin E level (200 mg/kg, as a positive control in each level of n‐6 to n‐3 ratio) in a 2 × 4 factorial arrangement during 70 days of the experiment. Results showed that a decline in the n‐6 to n‐3 ratio led to a reduction in serum cholesterol concentration (p < 0.05) and an increase in serum HDL content (p < 0.05). Additionally, decreasing n‐6 to n‐3 ratio and increasing clove bud level caused a remarkable decline in serum aspartate aminotransferase (p < 0.05 and p < 0.001) and alanine aminotransferase (p < 0.05 and p < 0.05) enzyme activities. Furthermore, total antioxidant capacity (p < 0.05 and p < 0.001) as well as serum vitamin E concentration (p < 0.05 and p < 0.001) was decreased and enhanced by low n‐6 to n‐3 ratio diets (LRD) and clove bud powder respectively. Decreasing the n‐6 to n‐3 ratio lowered hepatic lipid (p < 0.05) and glycogen contents (p < 0.01) as well as tissue integrity (p < 0.05), and raised liver MDA concentration (p < 0.001), markedly. Nevertheless, increments in clove bud content led to a reduction (p < 0.01) in liver relative weight (p < 0.05) and hepatic fat vacuole numbers. In general, the best synergistic responses on modulating of blood lipids and serum enzyme activities were observed when the highest level of clove bud was supplemented in the diets with low n‐6 to n‐3 ratio. Likewise, antioxidant indices were improved by administration of dietary clove bud powder although feeding fish oil was observed to elevate the susceptibility of blood and hepatocytes to lipid peroxidation.     

Intestinal microbiota of broilers submitted to feeding restriction and its relationship to hepatic metabolism and fat mass: Fast‐growing strain

The present study was conducted to verify how feed restriction affects gut microbiota and gene hepatic expression in broiler chickens and how these variables are related to body weight gain. For the experiment, 21‐d‐old Cobb500^TM birds were distributed in a completely randomized experimental design with three treatments: T1. Control (ad libitum—3.176 Mcal/kg ME—metabolizable energy—and 19% CP—crude protein); T2. Energetic restriction (2.224 Mcal/kg ME and 19% CP) from 22 to 42 days with consumption equivalent to control; T3. Quantitative restriction (70% restriction, i.e., restricted broilers ingested only 30% of the quantity consumed by the control group—3.176 Mcal/kg ME and 19% CP) for 7 days, followed by refeeding ad libitum from 28 to 42 days. Ileum and caecum microbiota collections were made at 21, 28 and 42 days of age. Hepatic tissue was collected at 28 and 42 days old for relative gene expression analyses. At 43‐d‐old, body composition was quantified by DXA (Dual‐energy X‐ray Absorptiometry). Both feed restriction programmes decreased Lactobacillus and increased Enterococcus and Enterobacteriaceae counts. No differences were found in the refeeding period. Energetic restriction induced the expression of CPT1‐A (Carnitine palmitoyltransferase 1A) gene, and decreased body fat mass. Quantitative feed restriction increased lipogenic and decreased lipolytic gene expression. In the refeeding period, CPT1‐A gene expression was induced, without changing the broilers body composition. Positive associations were found between BWG (Body Weight Gain) and Lactobacillus and Clostridium cluster IV groups, and negatively associations with Enterobacteriaceae and Enterococcus bacterial groups. In conclusion, differences found in microbiota were similar between the two feed restriction programmes, however, hepatic gene expression differences were only found in quantitative restriction. Higher counts of Lactobacillus and Clostridium cluster IV groups in ileum are likely to be related to better broiler performance and low expression of lipogenic genes.     

State‐of‐the‐Art‐Review: Immunomodulatory effects of opioids

Objective – To review the immunomodulatory effects of opioids. Data Sources – Original research publications and review articles using the PubMed search engine with the following keywords – opioids, morphine, immuomodulation, and immunosuppression. Veterinary and Human Data Synthesis – Opioids have been shown to modulate the immune system in animal models by affecting both the acquired and innate arms of the immune system. Natural killer cell activity, T‐cell proliferation, antibody production, phagocytic cell function, and cytokine production have all been shown to be affected by opioids. Many of these effects are reversed by opioid antagonists. Opioids have also been shown to induce sepsis in laboratory animals. Opioid administration alters immune parameters in healthy humans at analgesic doses and may increase the risk of infection in some patient populations. Conclusions – While opioids remain the most powerful and widely used analgesics available, their negative effects on the immune system are well established in the laboratory setting. Thoughtful consideration should be given to the use of certain opioids in critically ill patients, especially those with pre‐existing immunocompromise.