CASE IV:
Signalment
Five, 23-day-old, Commercial broilers, Gallus gallus
History
4 day illness reported by the overseeing veterinarian.
Gross Pathology
Field necropsy, no gross lesions provided.
Laboratory Results
None available
Microscopic Description
Liver: Multiple and often coalescing foci of necrosis (severity varies between sections) are randomly present throughout the section. The surrounding and intervening hepatocytes are often vacuolated (degenerate). Multifocally, hepatocytes contain round, amphophilic to basophilic smudgy intranuclear inclusion bodies that fill and expand the nucleus. Varying infiltrates of lymphocytes, plasma cells, and macrophages frequently expand the parenchyma. Medium to large numbers of lymphocytes and plasma cells as well as varying numbers of hematopoietic precursors expand portal and centrilobular connective tissues.
Contributor's Morphologic Diagnoses:
Liver: Multifocal to coalescing, variably severe, hepatic necrosis with intranuclear, basophilic inclusion bodies and marked lymphoplasmacytic to granulomatous inflammation
Contributor's Comment:
Fowl adenoviruses are a ubiquitous class of viruses that can cause a wide range of disease in poultry and other bird species including inclusion body hepatitis (most commonly serotype 8), gizzard erosion (most commonly serotype 1), and hydropericardium syndrome (most commonly serotype 4).4
Recent updates in taxonomic classification have identified the etiology of inclusion body hepatitis as Aviadenovirus hepatitidis (FAdV-E), serotypes 8a and 8b (FAdV-8a, -8b).2 The virus is transmitted horizontally by feco-oral routes and vertically from infected breeder hens shedding virus in eggs.6 Infected birds can shed virus for up to 6 weeks and it is fairly resistant once in the environment.6 Though any age or breed of bird can potentially be infected and develop clinical disease, young broilers 5-8 weeks old are most common.2-4,6 This is likely due to waning of maternal immunity. It is worth noting that birds infected vertically tend to develop disease at a slightly younger age. Once infected, the most common clinical sign is a sudden, dramatic increase in mortality, with loss of >30% of the flock possible. Grossly, animals with IBH often have pale, enlarged livers, but may also have mottled and enlarged kidneys and spleens.1 Atrophy of the thymus and bursa are variable and may be influenced by the presence of concurrent, immunosuppressive viral infections such as infectious bursal disease or chick anemia virus.4 Occasionally, multifocal petechiae are present in pelvic limb skeletal muscle. Histologically, there is acute necrosis in the liver with varying amounts of inflammation. Characteristic adenovirus inclusions are almost diagnostic in these cases. These are large, amphophilic to basophilic, intranuclear inclusions that often enlarge the nuclear contour enhancing their prominence. Less commonly, inclusions will occasionally be slightly eosinophilic with a clear halo resembling herpesvirus inclusions.1 Though the liver is consistently affected, viral inclusions and/or necrosis can also be variably observed in the pancreas, kidneys, gizzard, and intestines of infected birds.3 Diagnosis is typically reached via a combination of compatible gross and histologic findings and molecular diagnostics. There is no widely accepted treatment although supportive care may be warranted in clinically ill birds if they do not succumb to the infection. Prevention of clinical infection through vaccination and management of stress and concurrent disease are the goals of management practices.2,6 Vaccination of parent stock with autogenous vaccines developed via isolation of the challenge subtype virus from progeny has been shown to be effective in prevention of vertical transmission.5 It may also improve prevention of horizontal infection as well.
Contributing Institution
Department of Biomedical Sciences and Patholobiology VA-MD College of Vet Med, Virginia Polytechnic Institute and State University https://vetmed.vt.edu/
JPC Diagnoses
Liver: Hepatitis, necrotizing, subacute, multifocal to coalescing, random, moderate with numerous intranuclear viral inclusions.
JPC Comment
The genus Aviadenovirus, formerly classified as group I avian adenovirus, includes pathogens associated with inclusion body hepatitis, quail bronchitis, and hydropericardium syndrome. Siadenovirus, formerly group II avian adenovirus, includes turkey hemorrhagic enteritis virus (THEV), marble spleen disease (MSD) virus in pheasants, and the chicken "splenomegaly virus," which causes a disease resembling THEV and MSD. This genus is genetically distinguished by a sialidase-encoding gene and also includes a frog adenovirus. Atadenovirus, formerly group III avian adenovirus, includes the egg drop syndrome virus, which causes reduced egg production and thin-shelled eggs in its natural hosts, ducks and geese. The genus also includes viruses that infect mammals and reptiles.7
As noted by the contributor, IBH virus primarily targets hepatocytes, but pancreatic lesions are reported as well. Infection tends to occur in 3?7-week-old broiler chickens (although it has been reported in birds as young as 7 days and as old as 20 weeks) resulting in up to 30% mortality. It often occurs as a secondary infection in immunodeficient birds with other diseases, predominantly infectious bursal disease (birnavirus, serotype 1) and chicken infectious anemia (circovirus). Outbreaks of IBH with similar gross and histological lesions have also been reported in columbiformes, psittacines and raptors. 1,8,9 The recently identified falcon adenovirus, which is distantly related to fowl adenovirus types 1 and 4.
Infection with fowl adenovirus type 4 is the cause of hydropericardium syndrome virus (Angara disease), which is found in the Middle East10 as well as South America; particularly severe manifestations are also associated with immunosuppression. Lesions include pericardial effusion, pulmonary edema, hepatomegaly and renomegaly; mortality can range from 20-80%; and affected broilers are usually 3-5 weeks old.8 In this condition, the pericardium is filled with a straw-colored fluid and is accompanied by hemorrhage in the heart and pulmonary edema. Gross and histologic lesions typical of IBH are seen in this disease, and necrosis and inclusions may also be seen in the gizzard, pancreas, duodenum, proventriculus, cecum and kidney.10
In a retrospective study of IBH in chickens, Stoute et al. 11 identifies other histologic findings in almost 350 cases of IBH, including the presence of gizzard erosions (associated with inclusions within glandular epithelium) and glomerulopathy (characterized by inclusions in renal endothelium, expansion of the glomerulus with amorphous eosinophilic material, tubular dilation with hyaline cast formation, and urate tophi.11 Lymphoid tissue were diffusely depleted and the bone marrow was aplastic (with likely contributions by immunosuppressive birna- and circoviruses as mentioned above.)
References
- Abdul-Aziz, T., Fletcher, O. Hepatobiliary System. In: Abdul-Aziz, T., Fletcher, O, Barnes, H, ed. Avian histopathology (4th ed.). American Association of Avian Pathologists; 2016.
- De Luca C, Hess M. Vaccination strategies to protect chickens from fowl adenovirus (FAdV)-induced diseases: A comprehensive review. Vaccine. 2025 Jan 1;43(Pt 1):126496.
- Fitzgerald, Scott D. Adenovirus Infections. In: Swayne, David et al, ed. Diseases of Poultry (14th ed). John Wiley & Sons; 2020.
- Nakamura K, Mase M, Yamamoto Y, et al. Inclusion body hepatitis caused by fowl adenovirus in broiler chickens in Japan, 2009-2010. Avian Dis. 2011 Dec;55(4):719-23.
- Putnam M, Mills J, Markis M, El-Attrache J. Advancement of Autogenous Vaccines in the Poultry Industry. Avian Dis. 2024 Jan;67(4):450-455.
- Yugo DM, Hauck R, Shivaprasad HL, Meng XJ. Hepatitis Virus Infections in Poultry. Avian Dis. 2016 Sep;60(3):576-88.
- Wednesday Slide Conference 2015, Conf 25, Case 1.
- Wednesday Slide Conference 2013, Conf 16, Case 4.
- Adair BM, Fitzgerald SD. Group I adenovirus infections. In: Diseases of Poultry. 12th ed. Ames, IA: Iowa State Press; 2008:252-266.
- Alavizadeh H, Moosavi Z, Hashemi Tabar G. Investigating hydropericardium syndrome with different histopathological techniques in broiler chickens. Vet Res Forum. 2024;15(10):559-564. doi: 10.30466/vrf.2024.2023088.4174. Epub 2024 Oct 15. PMID: 39588465; PMCID: PMC11585847.
- Stoute ST, Crispo M, Crossley B, Jerry C, Rejmanek D, Blakey J, Nguyen V. Retrospective Study of Inclusion Body Hepatitis Diagnostic Cases in Chickens in California; 2015-2024. Avian Dis. 2025 Sep;69(3):281-287. doi: 10.1637/aviandiseases-D-25-00034. PMID: 41003432.