The liver is an astounding organ that has a part to play in 1,500 biochemical functions throughout the body. With a considerable blood supply, massive functional reserve capacity and the ability to fulfil combined digestive, waste-management, glandular and hormone-synthesising roles, it has a connection with most body systems in one way or another. No wonder liver cases present a unique clinical challenge.
For all we know of the liver’s function, we are still unaware of the exact mechanism by which triglycerides deposit within the hepatocytes of a feline hepatic lipidosis (FHL) case. While we don’t see this as a primary condition in dogs or humans, it’s not necessarily a disease specific to cats which are obligate carnivores either. It has also been observed in fasting guinea pigs, pregnant ewes, ponies and post-partum cows (Biourge, 2005).
What are the main causes?
A negative energy balance, usually caused by anorexia, is considered the primary cause for initiating FHL (Valtolina, 2017). As we expect and observe in other feline critical care cases, protein malnutrition occurs rapidly where inadequate calories are delivered.
In 5 percent of cases, FHL occurs in healthy, often overweight cats, anorexic and/or fasted for a prolonged period of time with no identified underlying disease. This form of the disease is called primary feline hepatic lipidosis.
In 95 percent of FHL cases, anorexia is triggered by pre-existing diseases, such as malabsorption/maldigestion disorders (often due to liver diseases, small intestinal diseases or pancreatitis), increased protein catabolism (neoplasia) or endocrinopathies (diabetes mellitus, hyperthyroidism) (Center, 1993). This form of the disease is called secondary feline hepatic lipidosis.
In both cases, the imbalanced catabolic process leads to mobilisation of peripheral fat stores and lipid oxidisation in the liver to fulfil gluconeogenesis. This process is particularly marked in overweight and obese cats who have greater adipose stores to contribute to the peripheral lipid load. As fat mobilisation overwhelms hepatic oxidisation capacity, triglycerides accumulate excessively in the hepatocytes’ cytoplasm, resulting in secondary impairment of liver function, and intrahepatic cholestasis. FHL is cytologically or histologically diagnosed when more than 80 percent of the hepatocytes are affected (Scherk and Center, 2005). Clinical signs commonly identified are jaundice, lethargy and hepatomegaly after an extended period, anorexia, rapid weight loss and vomiting (Figure 1). Grossly, the liver can double or even triple in weight due to triglyceride infiltration (Figure 2).
Treatment of the condition The pathophysiology of FHL is complex and not fully understood. However, we do know that aggressive nutritional management has a significant impact on outcome for patients with primary FHL. Three to eight weeks of tube feeding can reverse the condition in 80 to 85 percent of cases (Blanchard, 2004). In cases of secondary FHL, diagnosis and treatment of the primary underlying disease is crucial, alongside aggressive nutritional management. The outcome often depends on the nature and severity of the primary disease. The cornerstone of treatment in FHL is early nutrition. Aggressive nutritional management should be initiated on the day of admission to reverse the negative energy balance and catabolic state. The only reason for delaying nutrition is the presence of cardiovascular instability. In this case, hypoperfusion, hypotension and severe electrolyte abnormalities (hypokalaemia etc) would be addressed first. Overall, enteral feeding should be preferred over parenteral nutrition because it helps maintain intestinal structure and function (Valtolina, 2017). Force-feeding should always be avoided, as it may result in food aversion or aspiration pneumonia, particularly in nauseous anorexic patients with potentially decreased mentation. Additionally, adequate energy requirements are barely met in this way. So patent is this risk that it has been recommended that offering food per os for the first 10 days should be avoided (Biourge, 2005). Tube feeding is considered the gold standard approach to refeed these patients.
While refeeding syndrome is rarely observed in clinical practice, these cases are more prone than most. Food should be introduced over a four to seven-day period, with monitoring for phosphorus and blood glucose imbalances, as well as other complications associated with tube feeding (eg aspiration pneumonia and cutaneous abscessation at the site of the tube-feeding entrance).
Nasogastric tubes are often used in the first instance (Figure 3), particularly for immediate stabilisation in patients who are haemodynamically unstable to undergo general anaesthesia. As they are better tolerated in the long term, oesophageal or gastrostomy tubes are preferred, especially if the patient is stable enough to be managed at home with daily tube feeding, providing a good tolerance of the tube alongside their neck or abdominal dressing. Most cats will start to accept food after one to two weeks of enteral feeding, and as the condition resolves, the liver regains its normal histological structure, with regression of vacuolation after four to eight weeks (Rutgers, 2008).
Diet composition
The ideal diet for FHL should be high in protein (minimum 30 to 40 percent of the metabolisable energy), moderate in lipids (approximately 50 percent of the metabolisable energy), and poor in carbohydrate (approximately 20 percent of the metabolisable energy). Glucose should be used as a carbohydrate source because it does not require digestion and can be used by enterocytes as an energy source (Center, 2005; Amstrong, 2009). While these levels are found in most commercial cat foods, recovery and convalescent diets generally deliver calories in a more convenient and digestible format. Restriction of protein levels below 25 percent of calories (as per renal diets, for example) should be reserved only for those experiencing encephalopathy due to secondary liver failure (Biourge, 2005).
Cats with FHL are considered feeding-volume sensitive; they cannot tolerate large volumes of food per meal. The total volume of food required each day should be initially divided into six to eight portions, or administered as a constant rate infusion. Antiemetic medication is often provided alongside enteral nutrition to treat or prevent tube-feeding induced nausea or vomiting (Valtolina, 2017). The use of appetite stimulants is not recommended in this context.
How it can be prevented
The risk of FHL is increased in the obese cat. Not only are the consequences and associations with chronic, often insidious weight gain damaging to health, but equally compromising is the possibility of FHL. In overweight cats, fasting or brutal diet changes should always be avoided. Food intake should be monitored at any time, especially after stressful events, including environmental upsets we commonly associate with anxiety (moving home, introduction of a new child or pet etc).
Weight loss greater than 10 percent over a week is certainly cause for concern and intense monitoring
The risk of hepatic lipidosis is why we have weight loss maxima for healthy weight loss, commonly set at approximately 3 percent body mass loss per week. Weight loss greater than 10 percent over a week is certainly cause for concern and intense monitoring (Biourge, 2005). Because cats have a higher basal need for dietary amino acids, high protein, low calorie regimens are always a better strategy for weight management when selecting a clinical diet for this purpose.
As the hepatocytes of cats with FHL often have reduced endogenous antioxidants (vitamin E and glutathione) as well as low carnitine levels, supplementation is recommended at a preventative level (Blanchard, 2002; Center, 2002; Valtolina, 2017). The use of supplementation in management of the condition remains controversial, however the use of B vitamins is advised given rapid depletion of hepatic stores (Rutgers, 2008).
It’s important that the healthcare team appreciates the road to recovery for FHL cases. Success comes with patience. In cases of primary FHL, the outcome depends on monitoring of the consequences of the many possible metabolic processes occurring within our patients, and early aggressive nutritional management. Weeks to months of consistency as well as a long-term view of reducing disease risk and recurrence will lead to greatest clinical outcome.
