Introduction

The commonest canine liver disease is chronic hepatitis (CH) which is sometimes copper associated but usually 'idiopathic' with no identifiable cause. In those cases, specific treatment is not possible. Nevertheless, many dogs with CH can enjoy a good quality of life for long periods provided that the clinical complications of the disease are managed. Conversely, failure to address serious complications of liver disease such as malnutrition and portal hypertension with gastrointestinal ulceration will lead to premature death of the patient. The clinician needs to be aware of these potential problems and not only treat them, but also avoid precipitating them with inappropriate treatments.

Malnutrition

Protein-calorie malnutrition is very common in dogs with CH, as a result of reduced intake due to anorexia, vomiting and diarrhoea, and increased loss/wastage of calories due to hypermetabolism and poor liver function. Protein-calorie malnutrition is likely to have a serious impact on longevity and quality of life in affected dogs. Malnutrition is also recognised in dogs with congenital portosystemic shunt (PSS), both as a result of reduced liver synthetic capability and inappropriately severe protein restriction by the clinician. The treatment is clearly to feed the patient a sufficient diet. Protein restriction should be avoided as much as possible - and in some cases of CH associated with obvious cachexia, supplementation of a maintenance diet with extra high-quality protein (such as soya or dairy protein) is even indicated. If the patient will not eat voluntarily, some form of tube feeding should be instituted short term.

Portal Hypertension

The hepatic portal vein makes up 75% of the total hepatic circulation. In normal dogs, the multiple branches of the portal vein reduce the overall resistance to blood flow (circuits in parallel reduce resistance), and therefore the pressure in the portal vein is maintained at a level lower than that in the caudal vena cava. Diseases that obstruct flow through the intrahepatic branches of the portal vein or sinusoids elevate this pressure and result in significant portal hypertension. Most commonly in CH this occurs as a result of fibrosis.

Sustained portal hypertension results in splanchnic congestion and poor intestinal blood flow. This results in ascites and an increased risk of gastrointestinal ulceration. Ascites only develops once there is activation of the renin-angiotensin-aldosterone system (RAAS) and sodium retention in the kidneys. Splanchnic pooling of blood reduces systemic blood pressure. This causes RAAS activation with increased renal sodium retention to maintain systemic blood pressure. This increase in vessel filling tips Starling's forces 'over the edge' in the splanchnic circulation and allows ascites to build up. This explains why aldosterone antagonists are particularly effective in treating ascites of liver disease. Initially, these can be combined with furosemide to increase efficacy but long term, spironolactone is usually sufficient alone. Furosemide used alone can result in a counterintuitive increase in ascites due to increased RAAS activation. It is important NOT to drain the ascites from these patients unless they can be given a concurrent plasma transfusion because paracentesis in a dog with liver disease usually results in a precipitous drop in blood albumin concentration.

Poor splanchnic blood flow also predisposes to gastrointestinal ulceration. Bleeding from oesophageal varices is a common cause of death in humans with portal hypertension. In dogs, upper gastrointestinal bleeding is also a common cause of death in CH and much of the management of a stable canine CH case should be aimed at preventing any ulceration. Thus, avoidance of ulcerogenic drugs is important wherever possible. Non-steroidal anti-inflammatory drugs (NSAIDs) should not be used in these dogs anyway because of the increased risk of hepatotoxicity. Steroids also increase the risk of ulceration so should not be used unless there is a very good indication. In fact, the author avoids steroids in any dogs with CH unless they have had a liver biopsy AND examination of the biopsy specimen confirms a dense lymphoplasmacytic infiltrate (i.e., autoimmune-like) and a lack of significant fibrosis. Steroids are contraindicated without a biopsy since no non-invasive test will predict whether the patient has cirrhosis or non-inflammatory fibrosis. Animals with severe fibrosis and cirrhosis derive no benefit from steroid therapy and in fact steroids are likely to hasten their death.

Sustained increases in pressure in the portal vein higher than the caudal vena cava also result in the development of multiple acquired PSSs as 'escape' valves extrahepatically between the portal vein and caudal vena cava. These are a good thing as they limit the gastrointestinal congestion and reduce the risk of ulceration but they obviously result in a risk of hepatic encephalopathy (HE). This is usually more subtle in older dogs with CH than in younger dogs with congenital PSS. However, the pathophysiology and medical treatment of HE in both congenital and acquired PSS is similar. The difference is that acquired PSSs are NOT amenable to surgery.

Hepatic Encephalopathy

Traditionally, treatment of HE relied on feeding a low-protein diet little and often combined with antibiotics and lactulose. However, it is known that dogs with congenital PSSs have normal to increased dietary protein requirements and also dogs with CH are predisposed to protein-calorie malnutrition. The emphasis in human medicine has moved away from dietary protein restriction in HE for the reasons outlined below and the author does not use protein restriction in dogs with congenital or acquired PSS but relies on feeding a digestible diet little and often and managing concurrent inflammatory disease.

Ammonia is the key toxin in HE. Ammonia originates from a number of sources, varying between patients. In most dogs, the primary source is the gut, but a significant amount can also be derived from breakdown of body protein in protein-calorie malnutrition. Gut-derived ammonia was traditionally assumed to be a by-product of intestinal bacterial metabolism in the colon. This remains an important source in some conditions such as uraemia and melaena. However, recent studies in other species suggest that small intestinal enterocyte metabolism of glutamine as their main energy source is the most important source of postprandial ammonia absorption in the portal vein. Some dietary protein sources appear to be better than others in dogs with HE. Dogs on soya protein diets show a lower plasma ammonia concentration than those fed meat protein. An additional important trigger for HE in humans and rodents is inflammation: recent studies have confirmed that inflammatory cytokines are synergistic with ammonia in precipitating HE and that controlling inflammation in other organs is an important part of managing the patient with HE. There is anecdotal evidence that this is also true in dogs. The management of HE can be summarised as follows:

 Manage precipitating factors - most cases are actually precipitated by inflammatory disease elsewhere and management of this will often resolve the HE.

 Give appropriate fluid and electrolyte therapy. Dehydration, hypokalaemia and alkalosis will precipitate HE. Hypoglycaemia will worsen the outcome. It is therefore very important to measure electrolytes and blood glucose in these cases and supplement as necessary. Intravenous fluids are necessary in acute cases, appropriately supplemented. Animals which seizure (uncommon) can be treated initially with intravenous or per rectal diazepam, although this is often ineffective because of the effect of HE on the benzodiazepine receptor. If this is not effective, propofol infusions are usually efficacious.

 Treat and prevent constipation. Lactulose is still often used in humans and animals. It has many theoretical benefits in maintaining soft faeces and reducing ammonia absorption, although experimental evidence for its efficacy is lacking. In acute cases, lactulose enemas followed by per rectal administration of neomycin can be very helpful.

 Consider antibiotic therapy: ampicillin is often used in small animals and is proposed to reduce ammonia production in the intestine, but perhaps in many cases it is also efficacious as it reduces any other bacterial infections which precipitated the HE in the first place. Neomycin is a good short-term choice. There is some limited evidence in support of probiotics in humans but no work in dogs. Rifaximin is the current antibiotic of choice in humans with HE but is not licensed for use in dogs and there are no studies on its use in this species.

 Do not starve your patient: institute little and often feeding of a moderate-protein, highly digestible diet as soon as possible - remember that ammonia production as a result of negative nitrogen balance (i.e., protein-calorie malnutrition) will precipitate HE just as easily (perhaps more easily!) than intestinal feeding.

Coagulopathy

Coagulopathies are commonly recognised in liver diseases: they are commoner in acute than chronic disease and more often recognised in cats than in dogs. Nevertheless, it is very important to check coagulation times prior to any surgery or biopsy in dogs with liver disease and to treat any that are recognised. Vitamin K supplementation may be enough but often animals require a plasma transfusion. Coagulopathies in CH appear to be a poor prognostic indicator and are often associated with end-stage disease.

References

References are available upon request.