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Genome-wide based model predicting recovery from portosystemic shunting after liver shunt attenuation in dogs.

ABSTRACT: BACKGROUND:In dogs with congenital portosystemic shunt (CPSS), recovery after surgical CPSS attenuation is difficult to predict. OBJECTIVES:Our aim was to build a model with plasma albumin concentration and mRNA expression levels of hepatic gene products as predictors of recovery from portosystemic shunting after surgery. ANIMALS:Seventy-three client-owned dogs referred for surgical attenuation of CPSS. METHODS:A prediction model was constructed using 2 case-control studies of recovered and nonrecovered dogs after surgical CPSS attenuation. In the 1st study, a dog-specific gene expression microarray analysis was used to compare mRNA expression in intraoperatively collected liver tissue between 23 recovered and 23 nonrecovered dogs. In the 2nd study, preoperative plasma albumin concentration and the expression of microarray-selected genes were confirmed by RT-qPCR in intraoperatively collected liver samples of 31 recovered and 31 nonrecovered dogs, including 35 dogs from the 1st study. RESULTS:In the 1st study, 43 genes were differently expressed in recovered and nonrecovered dogs. The mean preoperative plasma albumin concentration in recovered dogs was higher compared to nonrecovered dogs (23 and 19 g/L, respectively; P?=?.004). The best fitting prediction model in the 2nd study included preoperative plasma albumin concentration and intraoperative DHDH, ERLEC1, and LYSMD2 gene expression levels. CONCLUSION AND CLINICAL IMPORTANCE:A preclinical model was constructed using preoperative plasma albumin concentration and intraoperative hepatic mRNA expression of 3 genes that were unbiasedly selected from the genome to predict recovery from portosystemic shunting after shunt ligation. Further development is essential for clinical application.

SUBMITTER: Van den Bossche L

PROVIDER: S-EPMC6060332 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Genome-wide based model predicting recovery from portosystemic shunting after liver shunt attenuation in dogs.

Van den Bossche Lindsay L van Steenbeek Frank G FG Weber Maarten F MF Spee Bart B Penning Louis C LC van Sluijs Freek J FJ Zomerdijk Flin F Groot Koerkamp Marian J A MJA Rothuizen Jan J Burgener Iwan A IA Kummeling Anne A

Journal of veterinary internal medicine 20180517 4

<h4>Background</h4>In dogs with congenital portosystemic shunt (CPSS), recovery after surgical CPSS attenuation is difficult to predict.<h4>Objectives</h4>Our aim was to build a model with plasma albumin concentration and mRNA expression levels of hepatic gene products as predictors of recovery from portosystemic shunting after surgery.<h4>Animals</h4>Seventy-three client-owned dogs referred for surgical attenuation of CPSS.<h4>Methods</h4>A prediction model was constructed using 2 case-control ...[more]

PMID: 29770973

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Project description:Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder.

Project description:BackgroundThere is limited information regarding percutaneous transvenous coil embolization (PTCE) for single extrahepatic portosystemic shunt (PSS). This study aimed to describe the procedure and outcome of PTCE in dogs with a single extrahepatic PSS. Forty-two privately owned dogs were included in this study. All dogs were diagnosed with extrahepatic PSS by computed tomography (CT). Preoperative CT images were used to evaluate the diameter of the PSS for coil placement. A multipurpose balloon catheter was percutaneously inserted into the PSS via the jugular vein, and transvenous retrograde portography (TRP) and measurement of blood pressure in the PSS (pPSS) were performed during balloon inflation; one or more embolization coils were implanted via the catheter.ResultsIn most cases, preoperative median fasting and postprandial serum total bile acid (TBA) concentrations were high (fasting, 86.5 μmol/L [ 3.7-250.0 μmol/L]; postprandial, 165.5 μmol/L [ 1.5-565.0 μmol/L]). CT revealed that 30 dogs had left gastrophrenic shunt; eight had left gastroazygos shunt; and one each had left gastrocaval, splenocaval, splenophrenic, and left colocaval shunt. TRP revealed that intrahepatic portal vascularity was clearly detectable in all dogs. The median values of pPSS before and during the balloon occlusion were 4.8 mmHg [2.0-13.0 mmHg] and 8.6 mmHg [5.0-18.0 mmHg], respectively. The median number and diameter of coils used were 2 coils [1 - 5 coils] and 8.0 mm [4.0 - 12.0 mm], respectively. The median times of irradiation and PTCE were 9 min [4-26 min] and 40 min [23-75 min], respectively. The median fasting and postprandial TBAs significantly decreased to 8.2 μmol/L [0.3-45.1 μmol/L, n = 38, p = 0.0028] and 19.8 μmol/L [0.3-106.7 μmol/L, n = 38, p = 0.0018], respectively, approximately 1 month after PTCE. The clinical success rate of PTCE without requirement for a second surgery was 95.2% (40/42 dogs). During revision surgery, one dog underwent surgical ligation and, in another dog, an ameroid constrictor was placed.ConclusionsPTCE was clinically effective in treating single extrahepatic PSS in dogs. Preoperative CT and TRP prior to PTCE might be clinically valuable for choosing the size of embolization coils, deciding the appropriate location of coil implantation, and estimating the number of coils to be implanted. PTCE is a promising alternative to conventional surgical procedures for single extrahepatic PSS in dogs.

Dataset Information

Genome-wide based model predicting recovery from portosystemic shunting after liver shunt attenuation in dogs.

Publications

Genome-wide based model predicting recovery from portosystemic shunting after liver shunt attenuation in dogs.

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