Common problems in poultry liver health and mycotoxin risk
The liver – a vital organ with numerous functions
The liver has various functions in digestion, metabolism and absorption, for example, metabolism of chemicals, absorption of protein, digestion of fat, metabolism of carbohydrate and absorption of vitamins. Almost all chemicals, including toxin components in the feed and chemical compounds in medicine are also metabolized and detoxified by the liver. All amino acids that are absorbed by the intestinal tract move to other organs through the portal vein in the liver, and catabolism of excess amino acids, uric acid formation from ammonia and albumin formation are also a major event occurring in the liver. As glycogen, an intermediate metabolite of carbohydrate, is synthesized and stored in the liver, it plays a major role in glycogenesis together with the pancreas. Fat soluble vitamins are also absorbed and stored in the liver. Erythropoiesis, the production of red blood cells, is also an important function of the liver. The liver thus performs numerous functions to maintain a proper body system, but poultry in modern production systems are facing a lot of challenges that threaten liver health.
Is the liver color revealing a healthy status?
Although the liver has so many essential functions for bird health, yet “physiologically normal” liver are rarely seen in field conditions because of frequent medication and exposure to toxic materials from the feed and the environment. Observation of liver color is the easiest and most reliable way to evaluate liver health. The liver could show various colors according to age, fat deposition, necrosis caused by viral infection, yolk absorption at an early stage and various other factors. Basically liver color observation should be done with a fresh sample within 30 minutes post mortem. Color changes in the liver could occur post mortem due to movement of red blood cell by force of gravity.
A healthy liver shows a yellow color until 8 to 10 days of age because of yolk content absorption (see Figure 1), but gradually changes to a brown color with age. Here then, a yellowish brown color would be regarded as an abnormal color of the liver, but it does not always means pathological conditions that require treatment.
Figure 1. Liver with yellow color in 4 day-old chick
Common diseases of the liver
Many of infectious and non-infectious factors could cause pathological changes in the liver, resulting in negative effects that impact the normal function of the liver.
1) Hepatitis E Virus infection
Avian Hepatitis E Virus (aHEV) is an infectious viral agent associated with big liver and spleen (BLS) disease and hepatitis-splenomegaly syndrome (HSS) (see Figure 2). It causes egg production drop in layer and breeder flocks with 1-5% mortality, and shows hepatic amyloidosis lesion in histopathological observation. As aHEV is genetically related to the human Hepatitis E Virus, several studies showed the possibility of cross-species infection between poultry and humans. aHEV infection usually occurs only during the laying period of layers and breeders.
Figure 2. Hepatomegaly and splenomegaly with non-specific inflammation and amyloidosis by aHEV infection
2) Fowl Adenovirus infection
Fowl Adenovirus (FAdV) infection is emerging problem in many of the Asian countries, causing serious economic losses in countries where a commercial vaccine is not available. All 12 serotypes of FAdV can cause Inclusion Body Hepatitis (IBH), but the serotype 4 virus also results in hydropericardium lesions together with IBH, and it is called Hydropericardium and Hepatitis Syndrome (HHS) (see Figure 3). Besides hepatic and cardiac lesions, FAdV infection shows pale and swollen kidneys, atrophy of immune organs and pinpoint white foci in the pancreas upon necropsy. It usually occurs in birds younger than 5 weeks of age, and is commonly spread by both horizontal and vertical transmission.
As all immunosuppressive agents or situations appear to facilitate FAdV in producing clinical signs and mortality, the prevention of infectious immunosuppressive diseases (such as Chicken Anemia Virus, Infectious Bursal Disease), the reduction of stress, and the removal of risks from mycotoxins in feed are very important ways to reduce economic losses from FAdV.
Figure 3. Various gross lesions observed in Fowl Adenovirus infection
3) Fatty Liver Hemorrhagic Syndrome
Fatty Liver Hemorrhagic Syndrome (FLHS) is a metabolic disease commonly occurred in long-lived birds such as breeders and layers. Lipogenesis and secretion of lipoproteins are natural metabolic functions of the liver for accumulation of energy, and these are controlled by estrogen. FLHS occurs when the accumulation of fat in the liver is increased beyond its storing capacity, and it sometimes causes hepatic rupture and bleeding (see Figure 4). It is commonly seen in overweight birds during the laying cycle, and causes egg production drops with low mortality. High energy diets with high calorie/protein ratio, low calcium consumption, stress and mycotoxins are common predisposing factors that can facilitate the occurrence of FLHS. As a color change to yellow is an early sign of FLHS, regular monitoring during necropsy is recommended to detect the early phase of fatty liver.
Figure 4. Common gross lesions observed in birds with Fatty Liver Hemorrhagic Syndrome
4) Fatty Liver and Kidney Syndrome
Fatty Liver and Kidney Syndrome (FLKS) is caused by biotin deficiency at an early age, of younger than 2 weeks. Biotin, also known as Vitamin H or B7, is an essential vitamin that is important for skin formation and maintenance. Biotin deficiency in young birds causes low mortality (<2%) with skin disorders and hepatic lesions (see Figure 5). Biotin supplementation is a treatment option that shows good prognosis.
Figure 5. Hepatic lesions in a 4 day-old bird with Fatty Liver and Kidney Syndrome
5) Fowl Typhoid
Fowl Typhoid (FT) is a systemic bacterial disease caused by Salmonella enterica serovar gallinarum (SG). The outbreak of FT is characterized by sudden increased mortality with swollen liver and spleen (see Figure 6). Antibiotic therapy can contribute to controlling mortality, but re-occurrence is very common. Live vaccines and insect (poultry mite) control is recommended for prevention.
Figure 6. Swollen and necrotic liver and spleen in a bird infected with Salmonella gallinarum
6) Side effects from bacterins
Some inactivated vaccines, and even LPS (lipopolysaccharides) or more commonly known as endotoxins from Gram-negative bacteria also cause liver damage with hemorrhage (see Figure 7). The additional step of removing LPS at the vaccine manufacturing site is highly recommended to minimize these side effects.
Figure 7. Petechial hemorrhage in liver observed in a layer bird vaccinated with an inactivated E. coli vaccine
Bacterial infections, including Campylobacter hepatica and Pasteurella multocida also cause pathological changes in the liver.
Mycotoxin risks in poultry production
Mycotoxicoses is the general term used for toxic diseases caused by ingestion, inhalation, or direct contact of feed contaminated with one or more mycotoxins. The mechanisms of mycotoxin toxicity are not fully understood due to the diversity in their chemical structures and target organs. Most mycotoxins can cause lipid peroxidation, damage of membrane structures and their functions, and induce apoptosis leading to cellular necrosis in various organs. Mycotoxins may cause immunosuppression, hepatotoxicity, nephrotoxicity, neurotoxicity, and even genotoxicity.
1) Aflatoxin toxicity and liver health
Aflatoxins are known to have a hepatotoxic effect in poultry and also a hepatocarcinogenic effect in exposed animals. The most common pathological lesions associated with aflatoxicosis in poultry are found in the liver, lymphoid organs, and testes, often occurring over a period of chronic exposure. In acute-subacute aflatoxicosis, the liver appears enlarged, pale yellow in color, friable, and usually the gall bladder is also enlarged and filled with bile (see Figure 8). The pancreas is usually small and depigmented and there could be hemorrhages on subcutaneous tissue and muscles. In chronic aflatoxicosis, the liver is small, firm, and rounded. Sometimes this organ is very small, rounded, and rubbery, and often complicated with ascites and hydropericardium. The other consistent lesions in aflatoxicosis can be found in the bursa of Fabricius, thymus, and spleen, all of which appear smaller than normal. In male parent stock breeder birds, the size of the testes could also be significantly reduced.
Figure 8. Enlarged and pale yellowish liver with yellow nodules observed in birds fed with aflatoxin contaminated feed. Aflatoxins were detected in the feed at 153 ppb and 458 ppb respectively.
The metabolic pathway of aflatoxins could be different. Aflatoxin B1 can enter the cell and be metabolized via monooxygenases in the endoplasmic reticulum to hydroxylated metabolites, which are further metabolized to glucuronide and sulfate conjugates. Or it can be oxidized to a reactive epoxide state, which undergoes spontaneous hydrolysis to AFB1-8,9-dihydrodiol and bind to proteins, resulting in cytotoxicity. The epoxide version can react with DNA or protein, or be detoxified by an inducible glutathione S-transferase to the glutathione (GSH)-conjugate. Both the DNA adduct and the protein adducts have proven useful as biomarkers in humans and laboratory animals (see Figure 9).
Figure 9. Metabolic pathway of aflatoxins
2) Mycotoxin Survey of Asia from January to March 2019
The prevalence of aflatoxins in Asia (including Oceania) in the first quarter of 2019 is a 40% contamination rate of total samples, but if we break this down per country to show various percentages of aflatoxin contamination, we have in alphabetical order, the following results – Australia (10%), China (39%), India (88%), Indonesia (86%), Japan (2%), Malaysia (17%), New Zealand (10%), Philippines (41%), Taiwan (0%) and Thailand (37%) – therefore, proper mycotoxin deactivation is required to protect animals from the negative effects of mycotoxins, and especially aflatoxins, which is the most toxic of all mycotoxins (see Figure 10).
Figure 10. Mycotoxin survey results in Asia from January to March 2019
3) Mycotoxin risk management for liver health
Bentonite is a natural clay with varying properties depending on its origin. Not all minerals in the market sold as binders are composed of bentonite. Only very few bentonites fulfill the strict and selective EU requirement [Regulation (EU) No 1060/2013], and so far, only one managed to achieved the 90% aflatoxin adsorption level required to claim EU authorization. To minimize the negative effects (not only from aflatoxin but also other unidentified mycotoxins) on liver health, it is not only important to manage mycotoxin risks in the feed, but also crucial to protect the liver and support the immune function of poultry flocks throughout Asia.