Abstract
Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with liver disease. The pathogenesis of he is incompletely understood although ammonia and inflammatory cytokines have been implicated as key mediators. To facilitate further mechanistic understanding of the pathogenesis of HE, a large number of animal models have been developed which often involve the surgical creation of an anastomosis between the hepatic portal vein and the caudal vena cava. One of the most common congenital abnormalities in dogs is a congenital portosystemic shunt (cpss), which closely mimics these surgical experimental models of HE. Dogs with a cPSS often have clinical signs which mimic clinical signs observed in humans with HE. Our hypothesis is that the pathogenesis of HE in dogs with a cPSS is similar to humans with HE. The aim of the study was to measure a range of clinical, haematological and biochemical parameters, which have been linked to the development of HE in humans, in dogs with a cPSS and a known HE grade. One hundred and twenty dogs with a cPSS were included in the study and multiple regression analysis of clinical, haematological and biochemical variables revealed that plasma ammonia concentrations and systemic inflammatory response syndrome scores predicted the presence of HE. Our findings further support the notion that the pathogenesis of canine and human HE share many similarities and indicate that dogs with cPSS may be an informative spontaneous model of human HE. Further investigations on dogs with cPSS may allow studies on HE to be undertaken without creating surgical models of HE thereby allowing the number of large animals used in animal experimentation to be reduced.
Highlights
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which occurs in patients with significant liver disorders [1]
We hypothesised that dogs with spontaneous congenital vascular abnormalities termed portosystemic shunts (cPSS) would be a good model for human HE. This hypothesis is supported by our recent findings that dogs with cPSS have increased whole blood concentrations of manganese and that dogs with a cPSS have higher serum concentrations of C-reactive protein compared to dogs with a cPSS which were asymptomatic, observations which are similar to studies in human HE [9,11,30,31]. We investigated this hypothesis by measuring a range of clinical, haematological and biochemical variables, including plasma ammonia and sodium concentrations and systemic inflammatory response syndrome (SIRS) scores, in 120 dogs with a cPSS both with and without clinical signs of HE
It is important to acknowledge that several dogs with HE had a normal plasma ammonia concentration
Summary
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which occurs in patients with significant liver disorders [1]. Hepatic encephalopathy has been estimated to occur in approximately 30-45% of patients with cirrhosis and 10-50% of patients with transjugular intrahepatic portosystemic shunt, while minimal HE has been estimated to affect approximately 20-60% of patients with liver disease [3]. The estimated prevalence of chronic liver disease and cirrhosis in the United States is approximately 5.5 million cases and in 2003 there were over 40 000 patients hospitalized for a primary diagnosis of HE, resulting in total charges of approximately $932 million [3]. Due to the significant morbidity and mortality associated with HE, a large number of studies have been undertaken which have examined the pathogenesis of this disorder. Two controlled trials of ammonia administration to patients with cirrhosis did not document development of HE [7,8]
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