Fatty liver is most common in periparturient cattle. Although often considered a postpartum disorder, it usually develops prior to and during parturition. Endocrine changes associated with parturition and lactogenesis contribute to the development of fatty liver; however, inappetence almost always accompanies severe cases. Cows that are overconditioned at calving are most likely to develop fatty liver. The disease can develop whenever there is a decrease in feed intake and may occur secondary to the onset of another disorder. Cows that develop fatty liver at calving are more susceptible to ketosis.

Etiology

Fatty liver occurs during periods when blood nonesterified fatty acid (NEFA) concentrations are elevated. The most dramatic elevation occurs at calving when plasma concentrations are often >1,000 μEq/L. Concentrations can reach that level if the animal goes off feed. Uptake of NEFA by the liver is proportional to NEFA concentrations in the blood. NEFA taken up by the liver can either be oxidized or esterified. The primary esterification product is triglyceride, which can either be exported as part of a very low density lipoprotein, or be stored. In ruminants, export occurs at a very slow rate relative to many other species. Therefore, under conditions of elevated hepatic NEFA uptake and esterification, triglycerides accumulate. Oxidation of NEFA leads to the formation of CO₂ and ketones, primarily acetoacetate and β-hydroxybutyrate. Ketone formation is favored when blood glucose concentrations are low. Conditions that lead to low blood glucose and insulin also contribute to fatty liver because insulin suppresses fat mobilization from adipose tissue.

The greatest increase in liver triglyceride typically occurs at calving. The extent of feed intake depression before and after calving or during disease moderates the degree of triglyceride infiltration. Fatty liver can develop within 24 hr of an animal going off feed. Because of the slow rate of triglyceride export as lipoprotein, once fatty liver has developed, it will persist for an extended period. Depletion usually begins when the cow reaches positive energy balance and may take several weeks to fully subside.

Fatty liver is a consequence of negative energy balance, not positive energy balance. Energy consumption above requirements for maintenance and productive purposes will not directly result in deposition of triglyceride in hepatic tissue. Triglyceride deposition will occur only if the animal becomes overconditioned and consequently reduces feed intake.

Clinical Findings

There are no known clinical signs that are unique to cows with fatty liver. Fatty liver has been associated with low milk production, increased clinical mastitis, and poor reproductive performance. However, cause and effect has not been established. Metabolic consequences of triglyceride accumulation in the liver include reduced gluconeogenesis, ureagenesis, hormone clearance, and hormone responsiveness. Consequently, hypoglycemia, hyperammonemia, and altered endocrine profiles may accompany fatty liver.

Fatty liver is likely to develop concurrently with another disease, typically disorders that are seen at or shortly after calving. These include metritis, mastitis, displaced abomasum, acidosis, and hypocalcemia. Field observations suggest that response to treatment of concurrent disorders is poor if cows have extensive triglyceride infiltration of the liver. Cows that are slow to increase in milk production and feed intake after calving are likely to have fatty liver. However, fatty liver is probably the result rather than the cause of poor feed intake. Cows with fatty liver are more prone to develop ketosis. Fatty liver is often associated with obese cows and downer cows (see Bovine Secondary Recumbency). Overconditioned cows exhibit poor feed intake prior to and after calving and, therefore, are susceptible to fatty liver. Although overconditioned cows are likely candidates to develop fatty liver, it is not restricted to obese cows. Similarly, obese cows do not necessarily have fatty liver. It is unlikely that triglyceride accumulation in the liver is a direct cause of downer cow syndrome.

Diagnosis

Diagnostic tools for fatty liver are of limited value. Fatty liver is usually diagnosed after the animal has been off feed or has died because of another complication. A positive diagnosis does not mean that clinical signs of illness are the result of fatty liver, and misinterpretation of a positive diagnosis is common.

Liver biopsy is the only reliable method to determine severity of fatty liver in dairy cattle. Measurement of total lipid or triglyceride content by gravimetric or chemical methods after extraction from tissue by organic solvents is necessary for quantitative assessment; however, these assays are not routinely conducted in commercial laboratories. Estimation of triglyceride content by flotation characteristics of the tissue in copper sulfate solutions of varying specific gravity is rapid, easy, and available for use under field conditions.

Blood and urine metabolites or blood enzyme activity have been proposed as diagnostic tools. Blood glucose concentrations are low and blood NEFA and β-hydroxybutyrate concentrations are high when conditions are conducive to the development of fatty liver. Blood cholesterol concentration is usually low when fatty liver occurs, which may reflect an impaired ability of the liver to secrete lipoproteins. AST, ornithine decarboxylase, and sorbitol dehydrogenase are hepatic enzymes that may be positively associated with liver triglyceride and liver damage. Blood metabolites or enzymes are often unreliable indices of fatty liver because baseline (normal) concentrations vary tremendously among animals. The same problem exists when attempting to determine liver function by measuring sulfobromophthalein clearance from blood.

Measurement of plasma NEFA is a popular diagnostic tool for identifying herds that may be at risk of developing fatty liver. In addition to extreme variations in plasma NEFA concentrations among animals, there is extreme variation in a single individual, because concentrations increase dramatically immediately before and after calving. Therefore, a large number of animals must be sampled at a consistent time relative to calving. Care must be taken not to excite animals before sampling blood because NEFA increase rapidly in response to stress; samples should be drawn at standardized times using standardized procedures. The plasma NEFA concentrations at which triglyceride accumulates in the liver have not been established, but are probably ~600 μEq/L and above. These concentrations are common within 24–48 hr of parturition. However, prolonged exposure of the liver to concentrations >600 μEq/L will likely lead to fatty liver. Primiparous cows are less susceptible to fatty liver during periods of elevated plasma NEFA. Therefore, mature animals should be sampled when using plasma NEFA as a predictor of fatty liver. To screen a herd for the prevalence and severity of hepatic lipidosis, determination of plasma NEFA not earlier than 1 wk antepartum is recommended. Even though plasma NEFA is a direct parameter for the lipid mobilization and thus the liver lipid accumulation, after parturition the plasma β-hydroxybutyrate concentration has been found to more accurately assess the incidence and severity of hepatic lipidosis.

Microscopic evaluation can be used to estimate the volume of the tissue occupied by fat. Estimates obtained by this method agree fairly well with chemical determination of triglyceride when expressed as a percentage of tissue dry weight. Mild, moderate, and severe fatty liver are often defined as <20%, 20–40%, and >40% fat (percentage of cell volume) respectively, but these values have little meaning relative to impact on physiologic function or clinical signs of the animal. However, clinical signs potentially associated with fatty liver disease are rarely seen in animals with <10% fat in wet liver tissue. Use of ultrasonography as an alternative noninvasive procedure is being developed for determining the severity of fatty liver.

Prevention and Treatment

Reducing severity and duration of negative energy balance is crucial in the prevention of fatty liver. This can be achieved by avoiding overconditioning cattle, rapid diet changes, unpalatable feeds, periparturient diseases, and environmental stress. Cows within a herd should enter the dry period with an average body condition score (BCS) of 3–3.5 (scale 1 = thin, 5 = obese). Thin cows (BCS ≤2.5) can be fed additional energy during the dry period to replenish condition without fear of causing fatty liver. Overconditioned cattle (BCS ≥4.0) should not be feed restricted because this will promote fat mobilization from adipose tissue and elevate blood NEFA and liver triglyceride.

The critical time for prevention of fatty liver is ~1 wk before through 1 wk after parturition, when cows are most susceptible. Cows that are candidates for preventive measures are those that are overconditioned or are starting to go off feed. Glucose or compounds that can be converted to glucose by the liver can be administered IV. Propylene glycol, 10–30 oz, given as an oral drench, sid, during the final week prepartum has been effective in reducing plasma NEFA and the severity of fatty liver at calving. Propylene glycol can be fed, but feeding may not be as effective if the full dose is not consumed in a short period of time. Glycerin may be a less expensive alternative to propylene glycol. Sodium propionate is also a glucose precursor, but feeding can cause a depression in feed intake and reduce efficacy.

Glucose or glucose precursors are effective because they may cause an insulin response. Insulin is antilipolytic, ie, it decreases lipid mobilization from adipose tissue. Slow-release insulin compounds are available. A single 100 IU IM dose of a 24-hr slow-release insulin immediately after calving may be prophylactic. Higher doses may cause severe hypoglycemia and should not be used without concurrent glucose administration. Glucagon stimulates glycogenolysis, gluconeogenesis, and insulin production. In contrast to that in nonruminants, the lipolytic effect of glucagon in ruminants is negligible. Glucagon (10 mg/day, IV, for 14 days) is effective at reducing liver triglyceride. A more practical protocol for use of glucagon to prevent fatty liver has not been established. Niacin is an antilipolytic agent that may have potential for prevention of fatty liver, but unequivocal evidence supporting niacin supplementation of animals at risk is not available.

Minimizing stress is important for prevention of fatty liver. Sudden changes in environment should be avoided. For example, changes in ration, housing, temperature, herdmates, etc, may cause a reduction in feed intake and trigger catecholamine-mediated increases in fat mobilization.

Besides longterm IV infusion of glucagon, there is no proven treatment for fatty liver. Repeated IV bolus administration of 500 mL of 50% dextrose solution is commonly used in dairy practice and can be combined with administration of propylene glycol 250 mL, PO, bid. Dextrose administration at a continuous infusion rate of up to 40 g/hr IV suitable to increase the plasma glucose concentration to 100–150 mg/dL without surpassing the renal threshold for glucose can be used in a clinical setting. Although this treatment effectively suppresses lipolysis and ketogenesis, treatment-induced hyperglycemia is likely to negatively affect feed intake. It is therefore advisable to continuously reduce the infusion rate after 2–3 days and to determine whether the animal is able to maintain normoglycemia as the parenteral glucose supply decreases.

Use of glucocorticoids in cows with fatty liver is controversial because of the potential lipolytic effect. Recent literature suggests that short-term treatment with dexamethasone does not induce lipolysis in dairy cows. Besides their well-documented gluconeogenic effect and a potentially positive effect on feed intake, glucocorticoids decrease glucose uptake by the mammary gland and thereby reduce the energy drain into milk. In theory, effective treatments would be those that enhance lipoprotein triglyceride export from the liver. However, compounds that are known lipotropic agents in nonruminants have not been proved to be effective in ruminants. IV administration of choline, inositol, methionine, and vitamin B₁₂ are often suggested as treatments, but scientific data are insufficient to support their use. Oral administration of these compounds is not effective because they are degraded in the rumen. In essence, treatment is the same as prevention; attempts should be made to avoid negative energy balance and to minimize fatty acid mobilization from adipose tissue. Once positive energy balance is attained, liver triglyceride can be reduced significantly in 7–10 days.

Last full review/revision July 2011 by Walter Gruenberg