Abstract

Hepatic disease in the avian patient manifests with unspecific signs, making it difficult to differentiate from other conditions. This article will give a brief overview of the necessary and available diagnostic tests for a definitive diagnosis and subsequent treatment of hepatic disease in the avian patient.

Introduction

Hepatic disease in the avian patient manifests with unspecific signs, making it difficult to differentiate from other conditions.^1-3 Generally, clinical enzymology is utilised commonly, but despite massive interspecies inconsistencies, it also merely indicates hepatocyte injury, revealing nothing about the chronicity nor the severity of the lesion nor the functional status of the liver.^1-4 Diagnostic imaging is an excellent method for the diagnosis of hepatomegaly and ascites.^1,2 However, to obtain a definitive diagnosis for hepatic disease, a histological examination of a biopsy sample is required.^1-3 Treatment of hepatic disease includes palliative care of the patient, treating the specific illness and creating an optimal environment for healing and regeneration of the liver.⁵

Diagnosis

History

A thorough collection of information pertaining to the patient may provide clues regarding the duration, severity and possible inciting cause of hepatic disease.⁶ These include, but are not limited to signalment, ownership history, diet, reproductive status, habitat design and maintenance, exposure to other animals (both captive and wild birds), health status of other animals in the house/aviary, current medication and supplements, possible exposure to toxins and details regarding onset and progression of the clinical signs.^2,6

Clinical Signs

Clinical signs are vague and represent the typical "sick bird": anorexia followed by weight loss, depression, fluffed-up feathers, vomition, polydipsia and polyuria.^2,3,6

Integument signs include poor feather quality, darkening of feather pigment, abnormal moulting, beak and claw overgrowth, pruritus followed by feather plucking.^2,3,6,7 Hepatomegaly and ascites (distended coelom) may compromise respiration and circulation through direct pressure on the lungs, air sacs, and heart (due to the lack of a diaphragm), which manifests as dyspnoea.^2-4,6,8 Birds produce very little, if any, biliverdin reductase, which results in the incomplete degradation of erythrocytes, rendering biliverdin as the primary bile pigment.^2-4,6,8 Icterus (hyperbilirubinaemia), is therefore a rare and unlikely finding in the avian patient, since erythrocytes are not degraded to bilirubin, the primary bile pigment in mammals.^2-4,6,8 In light of this, biliverdinuria (a green or yellow colouration of the urates) is highly suggestive of severe hepatopathy, but can also be caused by prehepatic haemolysis.^2-4,6,8 Hepatic encephalopathy may ensue, resulting in tremors, seizures, and paresis.^2,3,6,8 Abnormal bruising may be seen due to coagulopathy caused by the failing liver's insufficient production of clotting factors.^6,8

Clinical Pathology

Haematology is nonspecific, but may provide information regarding the chronicity and underlying pathological condition (anaemia, dehydration or leukocytosis indicating a possible infectious or inflammatory cause).^3,6 The buffy coat can also be examined for parasites that may cause liver injury such as Atoxoplasma, Leukocytozoon and Plasmodium spp.^6,7

Biochemistry results may show hypocholesterolaemia, hypouricaemia, hypoglycaemia, and hypoproteinaemia due to loss of the liver's synthetic functions.⁶ Anomalies include hypercholesterolaemia (seen with hepatic lipidosis and bile duct obstruction) and hyperproteinaemia (hyperglobulinaemia as a result of hepatitis inducing an immune response).⁶ The biochemistry profile should be repeated during the course of the disease, to rule out misinterpretations.²

Elevated plasma enzyme activities indicate recent hepatocellular damage and may create adequate suspicion of liver disease, but since most enzymes are not specific and limited to one organ, these tests should accompany a full investigation with other diagnostic modalities to confirm the diagnosis.^2,3,7 In the avian fibrotic liver, the insult occurred in the past, likely to have caused a spike in enzyme levels, but since no active damage is underway, the current enzyme activity may be normal.^2,9 Plasma enzyme activity may also be falsely elevated with haemolysis and lipaemia.^2,3

 Aspartate aminotransferase (AST) is a very sensitive indicator for liver damage, but is not specific, as any muscle damage will also cause elevations of this enzyme.^1-3,6,9 To differentiate between liver and muscle damage, plasma creatinine kinase (CK) can be measured, since CK has high sensitivity and specificity for muscle damage.^1-3,6,9

 Glutamate dehydrogenase (GLD) and gamma glutamyl transferase (GGT) are the most specific indicators of avian hepatic disease.^1,2,6,9 Avian GGT activity however, is low.^2,9

 GLD is a mitochondrial enzyme released with severe hepatic necrosis, as is seen in Amazon parrots with Pacheco's disease.^2,6

 GGT is found in biliary and renal tubular epithelium, showing marked elevations with biliary obstruction or damage.^6,9

 Alanine aminotransferase (ALT) and lactate dehydrogenase (LD) have limited diagnostic value in the avian hepatic patient, due to its presence in almost all tissues.^1,2,6,9 However, decreased levels of AST and LD may indicate extensive loss of hepatocellular mass.⁶

Plasma bile acid concentration is an indication for the clearing capacity of the liver.¹ It is a specific and sensitive indicator of liver function through bile acid extraction, conjugation, and secretion.^1,6 Mild elevations may indicate focal neoplasia with functional hepatic mass remaining.³ Moderate to marked elevations may indicate severe loss of functional hepatic mass, as can occur with hepatitis, bile duct hyperplasia, or severe cirrhosis.³ Chronic disease processes are however not always shown clearly.² Lipaemia and haemolysis may cause a false increase in bile acid levels.³

Diagnostic Imaging

Two orthogonal whole body radiographs (ventrodorsal and lateral) are required to assess the liver size.^1,6,8 On the VD view, the normal liver will fall between two lines drawn connecting the shoulder and hip joints.^1,3,6,8 On the lateral view, the normal liver does not extend beyond the caudal aspect of the sternum.^1,6,8

Hepatomegaly is frequently seen, but does not imply underlying pathology.³ Loss of the cardiohepatic waist ("hourglass"), rounded liver edges and displacement of surrounding organs will be noted.^1,6 Care must be taken to differentiate apparent hepatomegaly from cardiohepatomegaly (congestive heart failure will result in secondary hepatic congestion) or proventricular enlargement (differentiated by means of contrast radiography, fluoroscopy, ultrasonography, or other advanced imaging modalities).^1-3,6,8 Symmetrical hepatomegaly may be an indication of infectious or metabolic processes, where asymmetrical hepatomegaly may indicate neoplastic or granulomatous processes.¹ Microhepatica is frequently seen in macaws and cockatoos fed only seed-based diets, with unknown clinical significance.^1,3

Ultrasonography can be challenging in avian patients due to their small size and interference from the air sacs.⁶ The normal liver is homogenous and finely granular (middle echogenicity).^1,8 Any change in echogenicity or size is significant.^1,8 Ascites, congestion of hepatic vasculature, and pathologic changes to the gallbladder (if present in species) may also be seen.¹ Ultrasound-guided coeliocentesis, fine-needle aspiration, and hepatic biopsy are useful diagnostic tools.⁶

Endoscopy and Biopsy

Diagnostic method of choice, endoscopy allows visual examination of the liver in situ and a biopsy for histological and microbiological assessment.^1,2,8 A biopsy sample can be obtained laparoscopically, by blind percutaneous technique, ultrasonographic guidance, or surgically.^1,2,6,8 Risks for this invasive procedure include haemorrhaging, perforation of other organs or air sacs resulting in asphyxiation secondary to leakage of ascitic fluid into the air sacs.^1-3,6 The procedure is contraindicated in patients with thrombocytopaenia or with a prolonged bleeding time.^2,3,6

Treatment

For orderly and functional regeneration of the liver to occur, the acinar architecture has to be maintained.^5,8 If the acinar structure collapses, regeneration might occur haphazardly or heal by fibrosis.⁵ If treatment can commence promptly after acute insult and is aimed at removing the inciting cause of the liver injury, fibrotic changes may be minimised, but after several weeks, fibrosis is irreversible.⁵

Once treatment is started, the patient and clinical parameters should be monitored.⁵

 Supportive treatment. A quiet, warm environment with oxygen supplementation should be provided.
Fluid therapy is essential to stabilise patients.⁵ In hypoglycaemic patients, 5% dextrose may be added to the fluids.^5,6 Colloids should be used in hypoalbuminaemic birds to prevent oedema.³
Vitamin supplementation is advised, especially water-soluble vitamins (B and C), vitamin E as an antioxidant, and vitamin K for coagulopathies.^2,5,6,8 Vitamins A and D should be avoided due to possible accumulation and toxicity.^5,6,8 Crop feed anorexic patients.^3,5 Limiting nutrients that should always be supplemented include biotin, choline, and methionine, as these are usually deficient in the hepatic patient.^3,5
Blood transfusions may be given to patients with anaemia or coagulopathies.^5,8
Coeliocentesis and furosemide are indicated to relieve dyspnoea in ascitic patients.^2,5
Hepatic encephalopathy should be treated with lactulose and a decreased protein diet to reduce blood ammonia levels.^3,5,6

 Treating specific condition. The clinician should always strive to achieve an aetiological diagnosis in liver disease; however, this is not always possible.⁵ Every effort should be made to eliminate this aetiological agent.⁵ It is outside the scope of this article to discuss targeted therapeutic plans for specific hepatic disorders.

 Creating a favourable healing environment for the liver. Ursodeoxycholic acid (UDCA) suppresses hepatic synthesis and secretion as well as intestinal absorption of cholesterol and is used for treatment of cholestatic and necroinflammatory liver diseases.^5,8 It may also have a cytoprotective effect by modifying noxious bile acids.⁸
Colchicine has antifibrotic effects through its induction of collagenase and has anti-inflammatory qualities.^5,8
Silibinin (extract from milk thistle) is an antioxidant, enhances protein synthesis and hepatocellular regeneration, protects against hepatotoxins, suppresses fibrogenesis and promotes fibrolysis.^5,8

Conclusion

With the multiple diagnostic modalities available at present, it is unacceptable and counterproductive to simply diagnose a patient with hepatopathy.⁵ An aetiological diagnosis will allow for specific therapy and, as a result, have a better prognosis for the patient.^5,8 However, without the supportive measures, treatment is unlikely to be successful.⁵

Acknowledgements

1.  Monica Burger, BSc, University of Pretoria

2.  Bird and Exotic Animal Hospital, Onderstepoort, Pretoria

3.  Johannesburg Zoo, Johannesburg

References

1.  Krautwald-Junghanns ME, Zebisch K, Pees M, Willuhn, J. Diagnosis of liver disease in birds by radiography and ultrasonography: under special consideration of ultrasound-guided liver biopsies. Seminars in Avian and Exotic Pet Medicine. 2001;10(4):153–161.

2.  Lumeij JT. Hepatology. In: Ritchie BW, Harrison GJ, Harrison LR, eds. Avian Medicine: Principles and Application. Lake Worth, FL, USA: Wingers Publishing, Inc.; 1994: 522–537.

3.  Lawrie A. Systemic non-infectious disease. In: Harcourt-Brown N, Chitty J, eds. BSAVA Manual of Psittacine Birds. 2nd ed. BSAVA; 2005: 245–265.

4.  Lumeij JT. Diagnosis of hepatobiliary disease. In: A contribution to clinical investigative methods for birds, with special reference to the racing pigeon, Columbia livia forma domestica. PhD Thesis, Utrecht University; 1987: 35–77.

5.  Doneley B. Treating liver disease in the avian patient. Seminars in Avian and Exotic Pet Medicine. 2004;13(1):8–15.

6.  Grunkemeyer VL. Advanced diagnostic approaches and current management of avian hepatic disorders. Veterinary Clinics of North America: Exotic Animal Practice. 2010;13:413–427.

7.  Kahn CM, ed. The Merck Veterinary Manual. 10th ed. Whitehouse Station, NJ: Merck & Co. Inc.; 2010.

8.  Doneley B. Avian Medicine and Surgery in Practice: Companion and Aviary Birds. London: Manson Publishing/The Veterinary Press; 2010.

9.  Dorrestein GM, De Wit M. Clinical pathology and necropsy. In: Harcourt-Brown N, Chitty J, eds. BSAVA Manual of Psittacine Birds. 2nd ed. BSAVA; 2005: 60–86.