Liver Disease

Liver disease is a relatively common problem in horses. Despite this, it can often be a real challenge to identify the underlying cause. The liver is the main organ involved in the accumulation, metabolism and distribution of nutrients within the body. The majority of nutrients absorbed from the gastrointestinal tract pass via the portal circulation directly to the liver where they are metabolised, repackaged and either stored or exported to peripheral tissues. The liver also has a vital role in detoxification of both endogenous and exogeneous substances. The liver acts as the ‘first line of defence’ for all toxic substances that are absorbed via the gastrointestinal tract. As a result of this, the liver can be injured by many substances that are absorbed within the horse’s diet. The presence of gastrointestinal disease with intestinal inflammation can also cause injury to the liver.

The following table details some of the possible causes of liver disease in the horse:

Clinical Signs and Diagnosis

Clinical signs of liver disease in the early stage are often vague and non-specific. Many horses that are experiencing low levels of hepatic injury do not show any clinical signs. Clinical signs can include weight loss, lethargy, anorexia, colic, icterus, photosensitisation or, in more advanced cases, hepatic encephalopathy and laryngeal paralysis.  The main image shows a horse with end stage liver disease and dramatic oedema of his abdomen.

Diagnosis of liver disease or injury can usually be made relatively simply by performing biochemistry on a blood sample. This usually reveals increased concentrations of hepatic enzymes including gamma glutamyl transferase (GGT), glutamate dehydrogenase (GLDH) and aspartate aminotransferase (AST). Analysis of bile acid and bilirubin concentrations can also provide more information about hepatic function. In horses with advanced hepatic disease other laboratory findings may include prolonged blood clotting times, hyperglobulinaemia and increased ammonia concentration.

Once it has been identified that a horse has hepatic disease or injury, then further diagnostic tests may be useful to help identify the underlying cause. The first question that it is often useful to answer is whether it is only an individual horse or a group of horses that are affected. The simple way to do this is to blood test a number of horses from the same environment. It is very common to identify a number of other horses that are subclinically affected. The presence of a group of affected horses suggests exposure to a common environmental toxin or infectious agent.

Hepatic ultrasound is a useful tool for an individual horse with liver disease. It allows assessment of hepatic size and parenchyma and can identify specific problems such as the presence of masses, dilated bile ducts or choleliths. Changes, however, are often subtle and non-specific and in the majority of horses, no specific abnormalities are seen. Hepatic biopsy can be used to help provide further diagnostic and prognostic information. This should always be done using ultrasound guidance. Histology can provide a specific diagnosis in some cases (for example ragwort toxicity, neoplasia) but usually does not identify aetiologic agent but provides useful information about the type of disease process and the severity of the underlying disease. This helps to formulate a treatment plan for an affected horse and provide prognostic information.

Identification of potentially toxic substances can be challenging. The first simple assessment may be visual assessment of the hay and pasture for evidence of toxic plants such as ragwort. A good history should be taken to evaluate the possibility of more unusual toxins such as arsenic or other heavy metals. Specific testing can then be carried out if indicated.

Mycotoxins

Mycotoxins are an important and often underestimated cause of liver disease in horses. They are harmful substances that are produced from moulds growing on crops either during growth, harvesting or storage. Environmental conditions can have a huge impact on the levels of toxins produced. Increased amounts of these substances are produced during times of ‘stress’ for example extremes of temperature, dry weather etc. Once produced, these toxins are very stable and survive on pasture/forage for long periods of time. They are also not degraded by the acid environment in the stomach. Rossdales Laboratories has teamed up with Alltech, who are world leaders in animal nutrition and mycotoxin management, to be able to provide comprehensive mycotoxin testing. This involves screening samples of feed (usually forage) for a huge panel of mycotoxins. This then enables a risk analysis to be carried out to assess the likelihood of mycotoxin-related disease.

In recent years, a number of newly discovered viruses have been associated with liver disease in horses. Equine parvovirus-hepatitis (EqPV-H) has been identified as a cause of Theiler’s disease (equine serum hepatitis) which is often, but not always, associated with recent administration of an equine biologic product (Divers et al, 2018). Clinical disease usually presents with signs of lethargy, anorexia, jaundice and in some cases hepatic encephalopathy, and is most commonly seen in North America. The mortality rate in clinical cases is high; however, recently infected horses can have subclinical hepatitis and present with elevated hepatic enzymes. Equine hepacivirus (EqHV) has also recently been discovered and is closely related to human Hepatitis C virus. Research into the role of this virus in equine liver disease is ongoing, however it may be associated with subclinical disease in horses that results in mild elevations in hepatic enzymes. Both EqPV-H and EqHV can be detected in clinically healthy horses which may act as carriers. Both viruses can be detected by PCR analysis of a serum sample or fresh liver tissue if a biopsy is being performed.

Parasitic infection may cause focal or multifocal hepatic disease but is rarely a cause of significant hepatic dysfunction or liver failure. Larvae of Parascaris equorum and large strongyles can migrate through the liver resulting in areas of focal hepatitis and fibrosis. Echinococcus granulosus can form hydatid cysts in the liver, which can be visualised on ultrasound examination, however these are usually an incidental finding. Liver fluke infection can occur in horses, particularly if co-grazing with ruminants, although it most commonly results in subclinical disease. Faecal analysis for fluke eggs is available but has low sensitivity due to intermittent egg shedding and the fact that many infections do not become patent. Serological testing is also available and can aid in diagnosis.

Primary bacterial hepatitis/cholangiohepatitis is rare in adult horses. Cholangiohepatitis can occur secondary to bile stasis (e.g. due to cholelithiasis, intestinal obstruction, obstructive hepatic neoplasia) and diagnosis is based on histopathological findings on liver biopsy and isolation of bacteria from fresh tissue samples. Bacterial isolates associated with cholangiohepatitis are most commonly enteric organisms, with ascending infection from the small intestine considered the most likely route of infection.

Cholelithiasis occurs infrequently in middle-aged to older horses and can be associated with bacterial cholangiohepatitis, which may predispose to cholelith formation. Cholelithiasis can be found at any level of the biliary tract and the presence of multiple choleliths is common. Choleliths may be clinically silent or can result in clinical signs of hepatic disease and colic, particularly if obstructing larger bile ducts. Ultrasonographic findings include hepatomegaly, increased hepatic echogenicity, distended bile ducts and visualisation of choleliths and histopathological findings can be supportive of the diagnosis.

Primary hepatic neoplasia (e.g hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma) is very rare in horses. Metastatic spread of malignant tumours (e.g. lymphoma, malignant melanoma) to the liver from another primary location is more frequently seen, however it is still uncommon. Ultrasound examination and targeting of specific lesions for biopsy and histological examination may be useful for antemortem diagnosis.

Summary

Investigation of liver disease in horses can be challenging. A careful history and physical examination is always the first starting point. Further investigation should be case-specific but may include blood testing, ultrasound or biopsy. Mycotoxin testing should be considered in horses which are affected as part of a group situation. Other useful tests include viral testing and liver fluke serology.

Please contact our medicine team if you wish to discuss a case or a referral.