Internal Medicine Service

Research into canine hepatic encephalopathy

Research by the Dick Vet’s Medicine Team, along with colleagues at Dick White Referrals and Davies Veterinary Specialists, has offered insight into why dogs may suffer from neurological abnormalities as a common complication of liver disease.

Im news story

Liver disease is an important cause of ill-health in dogs. One of the most common complications of liver disease in dogs is neurological abnormalities, such as lethargy, altered gait, confusion and stupor. This syndrome is often termed hepatic encephalopathy (HE).

The presence of HE in dogs with liver disease can have a significant impact on their quality of life. This syndrome is a particular problem in dogs with a congenital portosystemic shunt (cPSS) (shown by arrow on image above in a computed tomography reconstruction of a cPSS). This is one of the most common congenital disorders we diagnose in our hospital and is due to the presence of an abnormal blood vessel, which diverts blood from the intestines away from the liver.

Our previous studies have demonstrated that dogs with liver disease have high circulating concentrations of manganese. Abnormalities in manganese metabolism are well recognised in human patients with liver disease as well and occur because the liver cannot effectively regulate manganese metabolism in patients with significant liver disease. High manganese concentrations in the blood of dogs and humans with liver diseases is considered to be clinically relevant because nerve cells are particularly susceptible to manganese toxicity. Consequently, it has been widely speculated that manganese plays an important role in the development of HE in dogs and humans with liver disease.

However, it still remains unclear whether manganese plays a central role in driving HE or is simply an innocent bystander and just a metabolic consequence of liver disease. In our most recent study, we measured manganese concentrations in the blood before and after surgical attenuation of a cPSS. We found that reducing the volume of blood which was diverted away from the liver through the cPSS was associated with a significant reduction in the severity of HE. Importantly, we also found that that a hypermaganesemic state persisted despite surgical attenuation of the cPSS. Our study demonstrated that resolution of hepatic encephalopathy can occur without the correction of hypermanganesemia, indicating that increased manganese concentrations alone do not play a causative role in HE. This study represents an important contribution to our understanding of the causes of HE in dogs and will help guide us in our quest to develop therapies for this highly debilitating disorder.

The precise role of manganese in the development of HE in humans and dogs with liver disease has widely debated for many years. However, clarifying the role manganese plays in the development of neurological complications in humans with liver disease has proved to be highly problematic. Our study has clearly demonstrated that dogs with liver diseases and HE can be successfully treated without the resolution of the hypermanganesemic state. Taken with our other recent studies, our collective body of work highlights the key role of ammonia and inflammation play in the development of HE and reveals that whilst hypermanganesmia occurs commonly in dogs with liver disease, high concentrations of manganese is unlikely to be the sole driver of HE. As well as improving our understanding of the biology of this important disorder in dogs, we hope that our studies demonstrates to the wider biomedical community the value of studying spontaneous disorders in dogs. We hope this comparative biology approach will improve treatment outcomes for dogs and humans alike.

Dr Richard MellanbyHead of Small Animal Medicine

The paper is published in Metabolic Brain Disease and is available on link below:

Surgical attenuation of spontaneous congenital portosystemic shunts in dogs resolves hepatic encephalopathy but not hypermanganesemia.

You can also find previous manganese study papers in the Veterinary Journal and the Journal of Veterinary Internal Medicine, on the below links:

Plasma cytokine concentrations in dogs with a congenital portosystemic shunt.

Whole blood manganese concentrations in dogs with congenital portosystemic shunts.

You can find previous HE studies in PLoS ONE, The Journal of Small Animal Practice and Metabolic Brain Disease at the links below.

Attenuation of congenital portosystemic shunt reduces inflammation in dogs.

Whole blood manganese concentrations in dogs with primary hepatitis.

Dogs with congenital porto-systemic shunting (cPSS) and hepatic encephalopathy have higher serum concentrations of C-reactive protein than asymptomatic dogs with cPSS.