Signalment:  

3-week-old broiler chicken, (Gallus galls domestics).There was a sudden onset of mortality affecting 10% of the flock. Sick birds adopted a crouching position with ruffled feathers and died within 48 hours.

Gross Description:  

At necropsy, diffuse yellowish-pale, friable and swollen livers are seen. Multiple petechiae beneath the capsule are present in some livers.

Histopathologic Description:

There is a disruption of the hepatic parenchyma due to the presence of multifocal to coalescing randomly distributed foci of degenerated hepatocytes. These hepatocytes are swollen with hypereosinophilic and highly vacuolated cytoplasm, and a pyknotic nucleus with karyorrhexis and/or karyolysis. Associated with these foci and randomly scattered throughout the parenchyma are hepatocytes with marked karyomegaly, chromatin condensation at the nuclear membrane and large basophilic intranuclear inclusion bodies. There is a moderate lymphoplasmacytic and heterophilic inflammatory infiltrate in the periportal areas. Diffuse cytoplasmic vacuolation is observed within remaining hepatocytes. Occasionally, there is focal widening and infiltration of sinusoids with lymphocytes, heterophils and histiocytes.

Morphologic Diagnosis:  

Liver: Acute, severe, multifocal to coalescing necrotizing hepatitis with intranuclear inclusion bodies in hepatocytes.

Condition:  

Inclusion body hepatitis

Contributor Comment:  

Inclusion body hepatitis (IBH) is a viral disease produced by a member of the family Adenoviridae, genus Aviadenovirus,(1) which was first described in chickens by Helmboldt and Frazier in 1963.(3) IBH is a ubiquitous disease in commercial and farm birds,(1) although recently infection has also been demonstrated in wild and exotic birds, producing the same characteristic hepatic lesions.(5)

The liver is the primary organ affected.(1) The infection produces a multifocal necrotizing hepatitis with intranuclear inclusion bodies in the hepatocytes.(1,6) Within the literature, the description of these intranuclear inclusion bodies is variable; inclusions have been described as large and eosinophilic or basophilic, or irregularly shaped, but they always replace/peripherally displace chromatin, and produce significant karyomegaly.(1)

JPC Diagnosis:  

Liver: Hepatitis, necrotizing, diffuse, severe, with numerous hepatocellular intranuclear viral inclusions.

Conference Comment:  

Although tissue sections are somewhat poorly preserved, the characteristic microscopic features, including the presence of viral inclusions with corresponding karyomegaly and peripheralization of chromatin, are nicely demonstrated in this case. Furthermore, the image of the affected liver submitted by the contributor provides an excellent example of the gross findings classically associated with IBH in chickens. 

Members of the family Adenoviridae are non-enveloped, icosahedral, dsDNA viruses composed of four genera: Aviadenovirus (infects birds), Mastadenovirus (infects mammals), Atadenovirus (infects birds, mammals and reptiles) and Siadenovirus (infects birds, amphibians, reptiles); there is also a proposed fifth genus that includes adenoviruses of fish, such as white sturgeon adenovirus. Adenoviruses characteristically produce viral inclusion bodies within the host cell nucleus, where replication occurs.(4) Readers are urged to review WSC 2009-2010, Conference 9, case 3 for additional details regarding general characteristics of adenoviruses. See table 1 for a summary of select adenoviruses significant in veterinary medicine.

Important aviadenoviruses (subgroup I) include inclusion body hepatitis virus, quail bronchitis virus and hydropericardium syndrome virus. Turkey adenovirus 3, the causative agent of hemorrhagic enteritis in turkeys, marble spleen disease in pheasants and avian adenovirus splenomegaly in broilers, is a siadenovirus (subgroup II), while egg drop syndrome virus is a member of the genus Atadenovirus (subgroup III).1 The pathogenesis of subgroup I avian adenoviruses is less defined than that of subgroups II and III; however, in general, both vertical and horizontal (especially fecal-oral) transmission are thought to be important in all aviadenoviruses. 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)

The recently identified falcon adenovirus, which is distantly related to fowl adenovirus types 1 and 4 (see WSC 2007-2008, Conference 23, case 3) rarely causes necrotizing hepatitis and splenitis with characteristic intranuclear viral inclusions; stress related to shipping or breeding is a likely predisposing factor for clinical disease.(2) Quail bronchitis virus, caused by avian adenovirus 1, is a worldwide disease of both captive and wild bobwhite quail; birds present with respiratory distress, nasal discharge, coughing, sneezing, conjunctivitis and, occasionally in older birds, diarrhea. Mortality approaches 100% in the young, but falls below 25% in those older than 4 weeks. Microscopic findings include tracheitis, air sacculitis and enteritis, with characteristic intranuclear viral inclusions. Infection with fowl adenovirus type 4 is believed to be the cause of hydropericardium syndrome virus (Angara disease), which is found in the Middle East 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.(4)

Egg drop syndrome, an atadenovirus (subgroup III) recognized in chickens, ducks and geese results in the production of soft-shelled or shell-less eggs. It is suspected that the virus originated in ducks and was passed to chickens via contaminated Mareks disease vaccine produced with duck embryo fibroblasts; spread within flocks occurs through contaminated eggs, droppings and fomites. Egg drop syndrome has worldwide distribution except the United States and Canada. The siadenovirus (subgroup II), turkey adenovirus 3, produces splenomegaly, hemorrhagic enteritis and immunosuppression with secondary opportunistic infections in turkeys older than 4 weeks. A serologically identical virus also causes marble spleen disease in pheasants and splenomegaly in chickens. Microscopic lesions are similar in all species and include splenic reticuloendothelial hyperplasia with intranuclear viral inclusions and fibrinonecrotic, hemorrhagic enteritis. There is a vaccine available.(4)

Table 1: Select adenoviruses in veterinary species.(1,4)

Species	NameSpecies	Comment
Dogs	Canine adenovirus 1 Canine adenovirus 2 (mastadenovirus)	- Infectious canine hepatitis - Infectious canine tracheobronchitis
Horses	Equine adenovirus 1 & 2 (mastadenovirus)	- Asymptomatic or mild respiratory disease in immunocompetent hosts - Bronchopneumonia/systemic disease in Arabian foals with SCID
Cattle	Bovine adenovirus (mastadenovirus and atadenovirus)	- 10 serotypes - Asymptomatic or mild respiratory disease - Occasionally pneumonia, enteritis, keratoconjunctivitis in calves
Swine	Porcine adenovirus (mastadenovirus)	- 4 serotypes - Asymptomatic or mild respiratory disease/enteritis; rarely encephalitis
Sheep	Ovine adenovirus (mastadenovirus and atadenovirus)	- 7 serotypes - Asymptomatic or mild respiratory disease - Occasionally severe respiratory/enteric disease in lambs
Goats	Caprine adenovirus (mastadenovirus and atadenovirus)	- 2 serotypes - Asymptomatic or mild respiratory disease
Deer	Cervine adenovirus (Odocoileus adenovirus 1; atadenovirus)	- Vasculitis, hemorrhage, pulmonary edema
Rabbits	Adenovirus 1 (mastadenovirus)	- Diarrhea
Mice	Murine adenovirus 1 & 2 (mastadenovirus)	- Murine adenovirus 1: experimental infections - Murine adenovirus 2: enterotropic; causes runting in neonates
Guinea pigs	Guinea pig adenovirus (mastadenovirus)	- Usually asymptomatic; rarely pneumonia with high mortality, low morbidity
Chickens	Fowl adenovirus (aviadenovirus, atadenovirus and siadenovirus)	- 12 serotypes of aviadenovirus (inclusion body hepatitis, hydropericardium syndrome) - 1 serotype of atadenovirus (egg drop syndrome) - 1 serotype of siadenovirus (adenovirus-associated splenomegaly)
Turkeys	Turkey adenovirus 1-3 (siadenovirus and aviadenovirus)	- turkey adenovirus 3, siadenovirus (hemorrhagic enteritis, egg drop syndrome) - turkey adenovirus 1 & 2, aviadenovirus (depressed egg production)
Quail	Avian adenovirus 1 (aviadenovirus)	- 1 serotype, aviadenovirus (bronchitis)
Pheasants	- serologically indistinguishable from Turkey adenovirus 3 (siadenovirus)	- Siadenovirus (marble spleen disease)
Ducks	Duck adenovirus 1 & 2 (atadenovirus and aviadenovirus)	- 1: atadenovirus (asymptomatic or drop in egg production) - 2: aviadenovirus (rare hepatitis)

References:

1. Adair BM, Fitzgerald SD. Group I adenovirus infections. In: Diseases of Poultry. 12th ed. Ames, IA: Iowa State Press; 2008:252-266.

2. Dean J, Latimer KS, Oaks JL, Schrenzel M, Redig PT, W+�-+nschmann A. Falcon adenovirus infection in breeding Taita falcons (Falco fasciinucha). J Vet Diagn Invest. 2006;18:282-286.

3. Hollell J, McDonald DW, Christian RG. Inclusion body hepatitis in chickens. Can Vet J. 1970;11:99-101.

4. MacLachlan NJ, Dubovi EJ. Fenners Veterinary Virology. 4th ed. London, UK: Academic Press; 2011:203-212.

5. Ramis A, Marlasca MJ, Majo N, Ferrer L. Inclusion body hepatitis (IBH) in a group of Eclectus parrots (Eclectus roratus). Avian Pathol. 1992;21(1):165-169.

6. Randall CJ, Reece RL. Color Atlas of Avian Histopathology. Mosby-Wolfe, Times Mirror International Publishers Limited; 1996:95-96.

Click the slide to view.

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4-1. Liver

4-2. Liver

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