Nutritional Management Adapted to the Type of Liver Disease

5. Nutritional Management Adapted to the Type of Liver Disease

Acute Liver Diseases

Acute liver disease is most commonly caused by toxic injury, and less frequently by infection (e.g., infectious canine hepatitis, sepsis), trauma, heat stroke, or vascular compromise (Center, 1996b). The spectrum of disease can range widely, and signs vary from mild to fulminant hepatic failure. Vomiting and diarrhea are common, whereas HE, melena, hematochezia, and DIC may occur in acute liver failure.

Stabilization - Fluid therapy with a balanced electrolyte solution is necessary for initial stabilization. Potassium and glucose should be supplemented as appropriate, and correction may reduce the severity of HE. Vomiting may be controlled by anti-emetics (metoclopramide, 0.2 - 0.5 mg/kg q 6 - 8h IV, IM, PO), whereas gastroprotectants (ranitidine 2 mg/kg q 8 - 12h IV, PO) are indicated in dogs with bloody vomiting and/or diarrhea. Treatment of HE may be needed as outlined below, using lactulose and oral antibiotics.

Dogs with acute liver disease are typically hypercatabolic and need prompt nutritional intervention in order to prevent debilitating malnutrition. The liver has tremendous regenerative capacities, but this is dependent on the availability of sufficient nutrients.

Enteral Nutrition

Enteral nutrition via tube feeding of frequent meals (3 - 6 hrs) should be instituted when the dog remains anorexic after 48 to 72 hours (Michel, 1995), provided there is no intractable vomiting. Tube feeding is usually first started using a naso-esophageal tube; esophagostomy or gastrostomy tubes may have to be used at a later stage when the dog remains anorexic (see Chapter 14).

Dietary Management

Oral feeding should be started gradually with small frequent meals in order not to overload the liver's metabolic capacity. Half of the daily requirements should be fed initially, and this should be increased by 10% every day dependent upon the dog's response. The diet should contain normal amounts of protein (20%) if at all possible, since a positive nitrogen balance is essential for hepatic regeneration. Protein tolerance can be augmented by increasing caloric content (for instance by mixing a hepatic support diet with a convalescence diet) and/or using drugs to counteract hepatic encephalopathy (e.g., lactulose, oral antibiotics). Moderate protein restriction may be necessary in patients with persistent HE. However, in acute liver disease it is especially important not to over-restrict dietary protein, since this could result in endogenous ammonia production from protein catabolism as well as a reduction in the availability of protein for hepatocellular repair. The source of protein is also important, with milk and soy protein being better tolerated than animal protein.

The diet should also include free radical scavengers and antioxidants, such as vitamin E, vitamin C and SAMe. Ursodesoxycholic acid(10 - 15 mg/kg PO q24h) can be given as a hepatoprotectant in the subacute stage when serum bile acids remain high.

Chronic Liver Disease

Chronic hepatitis includes a diverse group of disorders characterized by mixed inflammatory cell infiltrates, in which lymphocytes and plasma cells predominate (Center, 1996b; Johnson, 2000). The etiology is often never determined. Documented causes include abnormal hepatic copper accumulation and drug- or toxin-induced hepatic injury (anticonvulsants). The presence of lymphocytic-plasmacytic infiltrates may be suggestive of an immune-mediated mechanism, but this is difficult to distinguish from immunological disease that occurs secondary to hepatocellular injury, due to release of liver antigens and subsequent antibody formation. The use of immunosuppressive therapy remains therefore limited to the few cases with clear lymphocytic-plasmacytic inflammation of unknown etiology (Center, 1996a; Center, 1996b), especially since immunosuppressents may have detrimental effects on liver function.

In case of acute liver failure, oral feeding must be reintroduced gradually, with frequent small meals so as not to overload the liver's metabolic capacity. (©Royal Canin).

Remember that glucocorticoids can have side-effects that may impact dietary needs, e.g., by aggravating HE, ascites, glucose intolerance and/or gastric ulceration (Laflamme, 1999). This disease is usually in an advanced stage when recognized, and prognosis is guarded.

Dietary Management - Nutritional therapy is particularly important in chronic liver disease. The amount fed should at first be based on an estimation of the patient's energy requirements (Table 7).

Energy

Every effort should be made to get the dog to eat voluntarily. Food should be palatable, at room temperature and be fed in small portions 3 to 6 times daily. Dogs that refuse to eat or consume insufficient amounts to meet minimum requirements may require tube feeding, usually initially via a nasogastric tube, in order to halt the vicious cycle of excessive muscle catabolism and worsening signs of liver dysfunction. If the dog remains anorexic, esophagostomy or gastrostomy tubes may have to be inserted in order to ensure continuing nutritional adequacy (see Chapter 14).

Liver biopsy of a dog suffering from chronic hepatitis, showing periportal inflammation with mononuclear inflammatory cells (H&E). (©C. Rutgers).

Protein

Dietary protein should ideally represent 17 - 20% of metabolic energy, be highly digestible and of high biological value. Protein restriction should only be instituted when there are signs of HE. Protein tolerance can be increased by administering lactulose (0.5 ml/kg orally three times daily), which may be combined with oral antibiotics (metronidazole 7.5 mg/kg q 12hr, or ampicillin 20 mg/kg q 8hr). Increasing dietary levels of vegetable, soy or dairy protein may also help to reduce the likelihood of HE.

Assessment of the protein-calorie adequacy of the diet is generally based upon weekly monitoring of body weight and serum albumin concentrations. Progressive hypoalbuminemia (in absence of proteinuria) is indicative of protein malnutrition and/or progressive liver disease.

Fiber

The diet should contain both soluble fiber, in order to promote an acidic colonic pH and decrease NH4+ absorption, and insoluble fiber, which helps to normalize transit time, prevent constipation and bind toxins. Foods low in fiber can be supplemented with psyllium (1 tsp per 5 to 10 kg bodyweight per meal).

Reversibility of Problems

Dietary management of dogs with chronic liver disease aims to maintain adequate body condition in order to support hepatic regeneration and reduce signs of hepatic encephalopathy.

Minerals and Vitamins

It is essential that the diet contains increased zinc levels and a mixture of antioxidants including vitamins E and C. Additional oral zincsupplementation (zinc acetate 2 mg/kg daily) may be helpful because it is an antioxidant that also has antifibrotic properties and can reduce the severity of HE.

Copper Toxicosis

Bedlington Terriers affected with primary copper toxicosis develop progressive liver disease and die within a few years. This disease in Bedlington Terriers has similarities to Wilson's disease in man but differs clinically and genetically (Brewer, 1998; Muller et al., 2003); the treatment is however similar. The role of copper in other breeds is less clear, although it is thought that in some breeds copper accumulation may contribute to the development of liver disease (e.g., West Highland White Terriers, Doberman Pinschers and Dalmatians) (Rolfe & Twedt, 1995; Webb et al., 2002; Spee et al., 2005). Quantitative determination of liver copper levels as well as histopathologic assessment is important in differentiating primary copper storage disease from secondary copper retention due to cholestasis. Dogs with secondary copper accumulates tend to have lower concentrations in the liver, rarely exceeding 2000 ppm, and a different localization of copper within the lobule (Center, 1996b; Rolfe & Twedt, 1995).

Bedlington Terriers suffering from copper intoxication syndrome may present toxic liver copper concentrations from age 2 to 4 years (Twedt et al., 1979). (© C. Rutgers).

Dietary Management

Diets for dogs with copper hepatotoxicosis should be low in copper while high in zinc, contain increased vitamin B levels and adequate levels of high quality proteins. Many canine diets contain copper well above the minimum required amount, and it is important to choose a diet with levels as low as possible. Feeding copper-restricted diets slows hepatic copper accumulation but does little to lower liver copper levels in already diseased dogs with large amounts of hepatic copper accumulation.

Dogs with severely increased liver copper levels (> 2000 ppm; normal less than 400 ppm) should be partially decoppered for 2 - 4 months using a copper chelator such as D-penicillamine (1015 mg/kg orally q 12hr). Subsequently, treatment with oral zinc, which blocks intestinal copper absorption by induction of copper-binding metallothionein, is continued lifelong (Brewer et al., 1992). Treatment of dogs with secondary copper retention involves addressing the primary cause, as well as measures to reduce the accumulated copper.

Prevention

Diets low in copper are essential in breeds known to accumulate copper or that have increased concentrations on biopsy. Bedlington Terriers that have been genetically assessed as being at risk of developing copper hepatotoxicosis should be fed a low-copper diet from a young age since copper accumulation happens early in life. Other foodstuffs (e.g., shellfish, liver), mineral supplements or water with a high copper concentration should also be avoided (Table 8). DNA testing may help to identify affected and/or carrier Bedlingtons.

Hepatic Encephalopathy (HE)

HE is a metabolic disorder affecting the central nervous system, which develops secondary to hepatic disease (Maddison, 2000). It is usually a result of congenital portovascular anomalies (congenital portosystemic shunts, microvascular dysplasia) and less commonly due to severe hepatocellular disease. Acquired shunts may occur in response to portal hypertension caused by severe chronic hepatitis, cirrhosis and fibrosis, and will also predispose to development of HE. Rarely, HE is due to urea cycle deficiencies as reported in Irish Wolfhounds (Rothuizen et al., 2001). Signs are typically intermittent, may be precipitated by a high-protein meal, and vary from anorexia, vomiting, diarrhea and polyuria/polydipsia to disorientation, apparent blindness and seizures. Stunted growth or failure to gain weight may occur in young dogs with congenital portovascular shunts. A high index of clinical suspicion is important, since appropriate management of HE will greatly improve the patient's demeanor and may restore appetite.

Dietary Modification

Protein Quantity

Dogs with HE are initially offered a highly digestible, protein-restricted diet (around 15 % ME), in combination with medication aimed at reducing ammonia production and colonic absorption (lactulose; oral antibiotics such as metronidazole or ampicillin) (Figure 8). High diet digestibility as well as the addition of moderate amounts of fermentable fibers is of added benefit in regulating the intestinal microflora. Frequent, small meals should be fed in order to limit the time between meals, which improves nutritional status and reduces catabolism (Laflamme, 1999). If the patient becomes neurologically asymptomatic, protein quantity is gradually and cautiously increased at weekly or biweekly intervals. Normal or near-normal maintenance protein requirements should be fed unless the animal again becomes encephalopathic, and in that case the medical treatment ought to be reinstituted and/or intensified. Serum proteins should be monitored to prevent hypoalbuminemia, in which case dietary protein content is increased in association with more aggressive adjunctive treatment. In dogs with refractory HE, protein quality may be modified by replacing animal proteins with vegetable (soy) and/or dairy proteins.

Figure 8. Overview of nutritional management of liver disease.

Maintenance of muscle mass and a positive nitrogen balance is essential in reducing the risk of hepatic encephalopathy (HE). Dietary protein should be restricted only as needed to prevent HE. Correction of enteric bleeding, constipation, infection, alkalosis, hypokalemia and azotemia is also important in reducing the risk of HE.

Protein Quality

In addition to a protein-restricted diet and adjunct medication, it can be helpful to replace meat proteins with highly digestible vegetable (e.g., soy isolate) and/or milk proteins (e.g., casein, cottage cheese) (Strombeck et al., 1983; Center, 1998).

Soluble Fiber

Addition of soluble fiber can be of benefit by acidifying colonic contents and minimizing ammonia absorption. Psyllium (1 - 3 tsp per 5 - 10 kg of weight mixed with food daily) also contains some insoluble fiber, which adds bulk to the stool and prevents constipation.

Drug Therapy

Adjunct medical therapy can increase protein tolerance. Lactulose is a synthetic disaccharide that is fermented in the colon, resulting in colonic acidification and reduced ammonia absorption. The starting dose is 0.25 - 0.5 ml/kg two to three times daily, which is titrated to produce two soft stools daily. Oral antibiotics (e.g., metronidazole 7.5 mg/kg q 8 - 12 hr or ampicillin 20 mg/kg q 8hr) are given during severe encephalopathic episodes in order to modify the enteric microbial flora that is responsible for the generation of ammonia and other toxins.

Homemade versus Commercial Diets

Commercial diets are preferred above homemade ones because they are nutritionally complete. Veterinary diets formulated for dogs with hepatic insufficiency are now available and meet the specific nutritional requirements of the liver patient. It is difficult to create homemade diets that are balanced enough to be used for prolonged periods (Laflamme, 1999).

In general, diets for dogs with liver disease should be highly digestible with a high energy density provided by fat and carbohydrates (Table 9). Moderate protein restriction may be necessary in dogs with clinically evident HE, but protein quality should be very high. In addition, the diet should contain high normal to increased levels of water-soluble vitamins, enhanced zinc (>43 mg/1000 kcal), restricted copper, restricted sodium (<0.5 g Na/1000 kcal) in case of ascites, and a moderate amount of mostly soluble fiber. Protein restriction should be avoided as much as possible, especially in dogs with acute inflammatory hepatic disease or necrosis.