Liver disease is a common cause of morbidity and mortality in dogs. Liver diseases can be
broadly classified into vascular abnormalities such as congenital portosystemic shunt (cPSS)
and parenchymal diseases such as primary hepatitis. cPSS are a well-recognised vascular
anomaly in dogs. Despite the importance of liver diseases as a cause of debilitating clinical
signs, little is understood about the pathophysiology of the complications of canine liver
disease and it is currently difficult to provide accurate prognostic information to owners of
dogs with liver disorders.
One of the most common complications of canine liver diseases is the development of
neurological signs termed hepatic encephalopathy (HE). The pathogenesis of HE is poorly
understood although increases in ammonia, manganese, gastrointestinal-derived endogenous
benzodiazepines, cortisol and altered tryptophan metabolism have been linked to the
development of neurological signs. Recent studies have also shown an association between
inflammation and HE in dogs with cPSS. However, little is known about the role of
manganese in the dogs with primary hepatitis and the relationship between inflammation and
liver disease has only been crudely assessed to date using tools such as the systemic
inflammatory response score.
A small number of studies have examined prognostic markers in dogs with liver disease.
However, none have examined the relationship between inflammation and outcome. This is
surprising given the accumulating data in human hepatology which indicates that the
presence of systemic inflammatory response syndrome (SIRS) is a common and debilitating
event in patients with liver diseases. For example, the presence of SIRS has been linked to the
development of complications such as HE and is associated with a poor clinical outcome in
humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome
in dogs with a primary hepatopathy is unknown.
This thesis aimed to advance understanding of the pathogenesis of hepatic encephalopathy in
dogs with liver disease. In addition, the thesis aimed to examine the relationship between
inflammation and clinical outcomes in dogs with liver disease. Specifically, the aim of this
body of work was to examine manganese and sodium metabolism in dogs with primary
hepatitis and to measure cytokines in dogs with a congenital portosystemic shunt. The final
aim was to examine the relationship between systemic inflammatory response scores to
clinical outcomes in dogs with a primary hepatitis.
This thesis demonstrated that a high SIRS score was associated with a poorer long term
survival in dogs with primary hepatopathies. Furthermore, IL-6 concentrations were
increased in dogs with a cPSS. Given the well-established role of IL-6 in the pathogenesis of
hepatic encephalopathy in humans with acquired liver disease, it is possible that IL-6 may be
important in the development of HE in dogs with a cPSS. This thesis also demonstrates that
whole blood Mn concentrations are increased in dogs with primary hepatitis and sodium
concentrations were rarely outside the reference range in dogs with primary hepatitis. This
finding is in contrast with the numerous studies of human patients with liver disease. Overall,
these findings highlight the potential role of dogs as a model to examine the pathogenesis of
liver disease in human health
