Fatty Liver Disease
Causes, symptoms, treatment and prevention of hepatic lipidosis
Fatty liver disease refers to the deposition and build-up of fat in the liver. Fatty liver is a transition phase disease induced by a negative energy balance in dairy cows. During this period, body fat is mobilised and transferred to the liver as non-esterified fatty acids (NEFA) where they are either metabolised to produce glucose, or if supply exceeds metabolic capacity, excess becomes deposited as triacylglycerols.
Cows with circulating NEFA exceeding 0.9 mMol are often at a high risk of developing clinical ketosis and fatty liver disease. Ketone bodies, a by-product of incomplete fat metabolism, are correlated with circulating NEFA levels and can be used as an indicator for ketosis or fatty liver disease development risk.
Fat build-up in the liver inhibits metabolic function and induces a negative cascade of events that often results in death. As clinical treatment is often unsuccessful, prevention is the most successful course of action. An optimal body condition score between 2.75 and 3.5 is considered optimal to reduce the risk of developing ketosis or fatty liver syndrome.
Causes of fatty liver disease
Fatty liver (hepatic lipidosis) disease is the result of the liver being unable to cope with the amount of fat entering the liver for metabolism to glucose. Over 50% of dairy cows are estimated to suffer some level of fat accumulation during the transition period (Jorritsma et al. 2001). Associated losses due to fatty liver disease are estimated to cost the dairy industry in the United States up to $60 million annually. (Shen 2018).
Risk of fatty liver begins when body fat reserves are mobilized in response to low energy intake by the cow. In the week prior to parturition the dry matter intake (DMI) and associated energy intake decreases, this induces mobilization of body fat to compensate for the energy deficit. After parturition, energy demands increase significantly to support milk production. As DMI tends to lag post-parturition, there is increased mobilization of body tissues to compensate for the energy deficit.
Cows with a higher body condition score (BCS) mobilize proportionally more body fat compared to those having a lower BCS. Moreover, the change in BCS or rate of fat mobilization is considered a significant factor in developing fatty liver and may have a genetic link, with some cows more prone to rapid fat mobilization (Jorritsma et al. 2001). Mobilized body fat circulates as non-esterified fatty acids (NEFA) with some taken up by the udder and excreted with the milk, however, the majority is transferred to the liver to be metabolized into glucose to support milk production.
Normally, the liver of a dairy cow contains less than 1% of fat, however, when circulating fat levels exceed the liver’s ability to metabolize NEFA, the excess is deposited within the liver as a triacylglycerol. Risk and severity of developing fatty liver syndrome and associated metabolic disorders is classed depending on the extent of triacylglycerol deposition in the liver (Table 1).
In general, circulating NEFA levels of 0.9mMol or greater are considered to place the cow at a high risk of developing clinical ketosis and fatty liver disease. As fatty liver disease and ketosis are closely related, early detection of elevated ketone body levels can give an indication of herd risk levels. Beta-hydroxybutyrate (BHB) is commonly measured in blood or milk to assess the risk of ketosis. Levels of BHB in excess of 2.5 mMol are considered to place the cow at a high risk of suffering from fatty liver disease (ECLINPATH, 2019).
Table 1. Categories of fatty liver in dairy cows. Adapted from Bobe et al. 2004
|Liver category||Liver TAG1|
(% wet weight)
|Urinary ketones||Feed intake/milk production||Health status /|
|Mild||1-5%||+||0||-||Centrilobular TAG infiltration|
|Moderate||5-10%||++||0||--||TAG infiltration throughout liver|
1 TAG = triacylglycerol
2 The +/- symbols indicate positive or negative association, respectively, with the number of symbols indicating relative association. 0 indicates no association
In addition to the risk of fat accumulation in the liver, mobilization of body fat is an anabolic process which induces an inflammatory response. The degree of the inflammatory response is related to the extent of body fat mobilization. Given that the immune system is normally suppressed around calving, a high inflammatory response can place the cow at heightened risk of developing other secondary metabolic related diseases at calving, such as high somatic cell count or mastitis, metritis or ketosis and fatty liver disease.
Occurrence of fatty liver disease are closely paralleled with those of ketosis, as both directly affect liver function.
Potential indications of clinical or sub-clinical fatty liver syndrome include:
- Depressed DMI
- Rapid or excessive BCS loss,
- Low milk yield
- High prevalence of other metabolic disorders in early lactation such as mastitis, retained placenta, and milk fever
As the symptoms of fatty liver disease are synonymous with ketosis, herd monitoring of transitional NEFA levels in blood, or BHB levels in milk or blood can be used to assess potential risk within the herd. New research indicates that fibroblast growth factor-21 and haemoglobin are both strongly correlated to development of fatty liver disease, however, no cow side tests are currently available (Shen et al. 2018). In the absence of regular herd NEFA or BHB monitoring, herd managers are reliant on the visual cues such as excessive BCS prepartum and rapid or excessive weight loss postpartum.
Once symptoms are present, liver damage has likely already occurred and impact on lactation production will depend on the severity. Post-mortem analysis can confirm diagnosis, as the liver of a cow suffering from fatty liver syndrome will be inflamed and have an orange-hued discoloration compared to the normal healthy deep purple color (Fig. 1a,b)
There are currently no treatments for clinical fatty liver disease, however, in mild cases, cows can recover. In cases of recovery, the risk of developing other metabolic related disorders, such as delayed fertility, low milk yield or udder health may increase and potentially lead to early herd removal.
The challenge for most herd managers and veterinarians is to identify the underlying causes leading to early herd removal. Even in the case of mild fatty liver syndrome, liver damage increases cellular stress and metabolic function is reduced. Certain combinations of essential oils, such as those in Digestarom® Dairy, having high antioxidant capacity can aid in reducing the cellular stress, however, liver tissue repair and recovery of metabolic capacity takes time and may even hinder potential milk production in next lactation.
Prevention of fatty liver disease
10 Tips to prevent fatty liver disease:
- Monitor body condition scores systematically
- Group heifers by nutritional needs
- Maintain ideal body condition score throughout the dry period
- Stimulate dry matter intake
- Feed highly palatable diets
- Minimize the use of feed fats
- Maintain effective fiber
- Use essential oils/phytogenic feed additives, Digestarom® Dairy and Levabon®
- Use autolyzed yeast feed supplements, Digestarom® Dairy and Levabon®
- Feed rumen protected choline, methionine or niacin in postpartum period
Excessive body condition at parturition leads to a higher rate and larger extent of body fat mobilization. Heifers are often at a higher risk due to excessive body weight gain leading up to calving, stressing the importance of systematic BCS monitoring and grouping heifers by nutritional needs. Multiparous cows are not exempt, as prolonged lactation periods tend to result in excessive BCS and a greater potential to end the lactation with a high BCS.
An ideal BCS should be maintained throughout the dry period as attempting to correct BCS during this short period can impact calf development potentially leading to calving dystocia.
High demand for glucose to support early milk production commonly exceeds the nutrient intake of the cow, thus body fat is mobilized to minimize this deficit. The underline goal for herd managers is to stimulate DMI in order to reduce the burden on mobilized body reserves. Diets should be highly palatable, with a high glucogenic potential from a combination of starch and sugars, while minimizing the use of feed fats.
Feed fats are discouraged as they increase liver cellular stress by adding to the pool of lipids to be metabolised by the liver. Effective fiber levels need to be maintained in order to increase palatability, but also to stimulate rumen motility and reduce the risk of developing sub-acute rumen acidosis. Novel feed additives, utilizing a combination of essential oils and other plant secondary metabolites, can stimulate rumen motility and DMI, as well as affecting the rumen microbial population to be more energy efficient, thus more dietary energy available to the cow.
The high antioxidative capacity of essential oils also serves to support gut integrity to reduce the risk of intercellular tight junctions from breaking down, leading to leaky gut syndrome. Yeast additives, autolyzed yeast particularly, act as a probiotic to stimulate fiber digestion, again to get the most nutrients and highest glucose potential from the diets as possible. The high concentration and accessibility of mannanoligosaccharides (MOS) and beta-glucans in autolyzed yeast increase their capacity to bind pathogens and stimulate immune cell response, thereby assisting to mitigate the inflammatory reactions induced by dietary or metabolic fluctuations often encountered during the transition period and in fact, throughout the lactation cycle.
Additional diet aids such as rumen protected choline, methionine and niacin can be fed during the postpartum period in order to enhance liver fat mobilization and reduce the risk of excessive fat deposition in the liver. The consequence of mobilizing fat from the liver is that most of this potential energy is excreted in the milk, with the remainder recirculating back to the liver to be either metabolised to glucose, or once again deposited. Hence, the focus is on increasing the DMI of a glucogenic diets, with minimal feed fat content.
Bobe, G. Young, J.W., Beitz, D.C. 2004. Invited Review: Pathology, etiology, prevention and treatment of fatty liver in dairy cows. J. Dairy Sci. 87:3105-3124
ECLINPATH, Cornell University College of Veterinary Medicine, eclinpath.com/chemistry/energy-metabolism/%ce%b2-hydroxybutyrate/
Jorritsma, R., Jorritsma, H., Schukken, Y.H., Bartlett, P.C., Wensing, Th., Wentink, G.H. 2001.
Prevalence and indicators of post partum fatty infiltration of the liver in nine commercial dairy herds in The Netherlands. Liv. Prod. Sci. 68:53-60.
Mulligan, F.J., and Doherty, M.L. 2008. Production diseases of the transition cow. The Vet. J. 176:3-9.
Shen, Y., Chen, L., Yang, W., Wang, W. 2018. Exploration of serum sensitive biomarkers of fatty liver in dairy cows. Sci. Reports. 8:13574-13571.