Hepatic cirrhosis in a cockatiel (Nymphicus hollandicus) from Brazil

Hepatic cirrhosis in a cockatiel (Nymphicus hollandicus) from Brazil | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Hepatic cirrhosis in a cockatiel (Nymphicus hollandicus) from Brazil Erick Platini, Artefio Oliveira, Débora Cardoso, Glauco Galiza, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8124577/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract A 17-year-old male cockatiel ( Nymphicus hollandicus ) was presented with a one-week history of apathy, inappetence, weakness, and reluctance to move, and died shortly afterward. Postmortem examination revealed an overweight body condition, ascites, and a markedly firm, shrunken liver with a diffusely irregular capsular surface and multifocal, well-defined green-to-yellow nodules. On cut surface, these nodules were soft, compact, yellow to tan, and extended deeply into the parenchyma. Histologically, the hepatic tissue was largely replaced by broad fibrous septa that enclosed distinct islands of hepatocytes forming regenerative nodules. Additional findings included bile duct hyperplasia and multifocal infiltrates of lymphocytes, plasma cells, and occasional macrophages. The remaining hepatocytes exhibited cytoplasmic degeneration or necrosis. Based on the clinical presentation and anatomopathological features, hepatic cirrhosis was diagnosed. Although considered uncommon in avian species, cirrhosis should be included in the differential diagnosis of chronic liver disorders, particularly in aged birds or those with a history suggesting prolonged hepatic injury. Avian disease hepatopathy fibrosis liver failure Figures Figure 1 Figure 2 Introduction The avian liver is responsible for a wide range of metabolic activities, including the synthesis, storage, filtration, and excretion of several nutrients and chemical compounds (Grunkemeyer, 2010 ). Consequently, hepatic dysfunction is considered one of the most significant medical problems in birds (Hochleithner et al., 2006 ). Its causes include congenital, infectious, and non-infectious disorders (Schmidt et al., 2015 ). Non-infectious hepatic diseases encompass lipidosis, hepatic atrophy, pigmentary hepatopathies, visceral urate deposition (gout), amyloidosis, lysosomal storage diseases, xanthomatosis, neoplasms, chronic-active hepatitis, and fibrosis (Schmidt et al., 2015 ). Regardless of etiology, the liver has substantial functional reserve and regenerative capacity, and only lesions affecting most of the hepatic parenchyma are likely to produce clinical signs of liver failure (Hochleithner et al., 2006 ). In general, destruction of the hepatic parenchyma triggers regeneration, biliary hyperplasia, and varying degrees of fibrosis (Hochleithner et al., 2006 ). Hepatic fibrosis is an uncommon histological finding in birds and often represents a nonspecific response to severe or repeated hepatic injury. Therefore, the present report details the clinical and anatomopathological features of end-stage liver disease in a cockatiel ( Nymphicus hollandicus ) from Brazil. Results A 17-year-old male cockatiel ( Nymphicus hollandicus ) was presented with a one-week history of apathy, inappetence, weakness, and reluctance to move. The bird had been with the owner throughout its life and had no prior history of illness. Its diet consisted mainly of a commercial seed mixture (sunflower seeds, birdseed, and oats), supplemented occasionally with bread, green corn, and cabbage. Fresh water was offered ad libitum, and a vitamin complex was provided twice a year. The cockatiel died shortly after presentation and was submitted for necropsy. Postmortem examination revealed an overweight body condition (90 g; body score 4/5). Significant gross findings included a clear, watery effusion within the coelomic cavity (ascites) and a markedly firm, shrunken liver with a diffusely irregular capsular surface. Multifocal, well-demarcated, mottled green-to-yellow nodules measuring up to 0.3 cm in diameter were scattered throughout the hepatic surface (Fig. 1 A and B). On cut surface, these nodules were soft, compact, yellow to tan, and extended deeply into the parenchyma. Samples of the skin, central nervous system, and organs of the coelomic cavity were fixed in 10% neutral buffered formalin, routinely processed for histology, embedded in paraffin wax, cut at 3 µm sections, and stained by hematoxylin and eosin (HE) and Masson's trichrome (MT). Histopathological evaluation revealed that approximately 80% of the hepatic parenchyma was replaced by extensive fibrous septa, which surrounded well-defined islands of hepatocytes (regenerative nodules) and extended toward the remaining portal triads (bridging fibrosis) (Fig. 2 A and B). These fibrous tracts frequently contained moderate bile duct proliferation and mild, multifocal inflammatory infiltrates composed of lymphocytes, plasma cells, and occasional macrophages. Within the regenerative nodules, the residual hepatocytes displayed macro- and microvacuolar cytoplasmic degeneration, sometimes accompanied by individual or small clusters of necrotic hepatocytes (Fig. 2 B and C). All other organs were unremarkable. The collagen strands within the fibrous septa were highlighted in dark blue in the MT-stained sections (Fig. 2 D). Discussion The diagnosis of hepatic cirrhosis was based on the clinical and anatomopathological findings. It seems to be a frequent condition in chronic liver diseases that the initial causative insults may precede any severe clinical signs and quickly disappear, which makes it very difficult to accurately identify the causes (Davies, 2000 ). However, the pathological findings of hepatic fibrosis with hepatocellular loss, bile duct hyperplasia, and multifocal chronic inflammation are suggestive of toxic hepatopathies (Lee et al., 2011 ). The diagnosis of hepatic cirrhosis was based on the clinical and anatomopathological findings. In chronic liver diseases, the primary injurious events often occur long before severe clinical signs become evident and may subside quickly, making the precise identification of the underlying cause particularly challenging (Davies, 2000 ). Despite this limitation, the pathological features observed in this case, including marked hepatic fibrosis associated with hepatocellular loss, bile duct hyperplasia, and multifocal chronic inflammation, are compatible with the morphological patterns typically described in toxic hepatopathies (Lee et al., 2011 ). These alterations reflect a prolonged reparative response to hepatocellular injury, ultimately leading to distortion of the hepatic architecture and progression to cirrhosis. Toxic injury to the liver has been reported in mammals secondary to exposure to a wide range of harmful agents, including mycotoxins, heavy metals such as copper, iron, selenium, arsenic, and mercury, as well as various chemicals and organic compounds such as chloroform, chlordane, dieldrin, tannic acid, tetrachloroethane, dimethylnitrosamine, carbon tetrachloride, coal tar pitch, and gossypol. Similar lesions may also occur in association with nutritional deficiencies, particularly of methionine and choline (Clyde et al., 1996 ). Common hepatotoxins in pet birds include mycotoxins such as aflatoxins and citrinin (Clyde et al., 1996 ). Cockatiels, in particular, are highly sensitive to aflatoxins, and it has been proposed that chronic-active hepatitis in this species may arise from prior exposure to these toxins (Schmidt et al., 2015 ). In this case, the toxic hepatopathy was likely caused by the daily seed mixture, which was possibly stored under improper conditions, allowing fungal proliferation and toxin production. Liver disease in mammals disrupts several critical physiological processes and may manifest as hepatic encephalopathy, ascites, jaundice, hemorrhagic diathesis, hepatogenous photosensitization, hepatorenal syndrome, and hepatocutaneous syndrome (Cullen & Stalker, 2016). In birds, however, there are no pathognomonic clinical signs of hepatic dysfunction (Grunkemeyer, 2010 ). In this case, the cockatiel showed several nonspecific signs, including apathy, reduced appetite, and weakness. Ascites was present, although it was not clinically apparent. In addition, jaundice is not a typical manifestation of hepatic disease in birds because biliverdin, rather than bilirubin, is the predominant bile pigment (Hochleithner et al., 2006 ). Therefore, the diagnosis of liver disease in avian species should rely on the integration of multiple diagnostic approaches, including physical examination, clinicopathologic testing, imaging studies, and, when feasible, hepatic biopsy (Grunkemeyer, 2010 ). Among the available laboratory tests, plasma bile acid measurement is considered a more accurate and specific prognostic indicator in cases of acute hepatitis (Lee et al., 2011 ). In the present case, no plasma biochemical analyses were performed. Nonetheless, it is important to note that in patients with end-stage liver disease, liver enzyme activities may be normal or even decreased, as active hepatocellular injury may no longer be occurring (Wheler & Webber, 2002 ). Hepatic biopsy is often necessary for the definitive diagnosis and proper characterization of liver disease (Jaensch, 2000 ), as histopathological evaluation provides direct evidence of the severity and nature of the hepatic lesions. Biopsy samples can be obtained through blind or ultrasound-guided percutaneous techniques, endoscopic biopsy, or by performing a liver wedge biopsy during celiotomy (Lee et al., 2011 ). An interesting pathological finding was the partially mottled green appearance of the liver. As previously noted, biliverdin is the principal bile pigment in birds and is responsible for its characteristic green coloration (Hochleithner et al., 2006 ). In cases where the normal hepatic architecture is replaced by structurally abnormal nodules, bile flow becomes impaired (cholestasis), which can ultimately alter the coloration of the organ. Histopathological examination revealed that most of the hepatic parenchyma had been replaced by fibrous tissue interspersed with regenerative nodules, while the limited remaining normal tissue contained degenerated and necrotic hepatocytes. Hepatic fibrosis represents a key stage in the progression of many liver diseases, and it is estimated that more than 80% of the liver must be affected before hepatic dysfunction becomes clinically apparent (Grunkemeyer, 2010 ). Differential diagnosis should include hepatic lipidosis, hepatic neoplasia, and bacterial, viral, or chlamydial hepatitis (Wheler & Webber, 2002 ). However, the histopathological findings in this case, marked by extensive fibrosis and only minimal inflammation, were sufficiently specific to establish the morphological diagnosis. Conclusion Although cirrhosis is an uncommon condition in birds, it should be considered among the differential diagnoses of chronic liver diseases. Unlike mammals, clinical signs in avian species are nonspecific, making the diagnosis of cirrhosis more challenging. Therefore, the use of multiple diagnostic methods is recommended, with anatomopathological evaluation providing the most reliable information regarding the characteristics and severity of the hepatic lesions. Declarations Ethics approval No ethical approval was required for this study, as this is a retrospective case report of a cockatiel referred for necropsy. Consent to publish Written informed consent has been obtained from the patient’s owner to publish this paper. Conflict of interest The authors declare that they have no conflict of interest. Funding No funding was obtained for this study. Author Contribution Clinical examinations were performed by AMO and DFC. The writing of the manuscript was carried out by EPFS, GJNG and AFMD. Figure preparations were carried out by EPFS and AMO. All the authors have read and approved the submitted version. Data Availability No datasets were generated or analysed during the current study References Grunkemeyer VL. Advanced Diagnostic Approaches and Current Management of Avian Hepatic Disorders. Vet Clin North Am Exot Anim Pract 2010;13:3:413–427. https://doi.org/10.1016/j.cvex.2010.05.005. Hochleithner M, Hochleithner C, Harrison LD. Evaluating and treating the liver. In: Harrison GJ, Lightfoot TL, editors. Clinical avian medicine, Palm Beach: Spix Publishing;2006,p.441-449. Schmidt RE, Drury RR, Phalen DN. Pathology of pet and aviary birds. 2nd ed. John Wiley & Sons, Inc. Published, 2015. DOI:10.1002/9781118828007. Davies RR. Avian Liver disease: etiology and pathogenesis. Semin Avian Exotic Pet Med 2000;3:115-125. https://doi.org/10.1053/ax.2000.7138. Lee SY, Kim DY, Park HM. Hepatic Fibrosis and Bile Duct Hyperplasia in a Young Orange Winged Amazon Parrot (Amazona amazonica). J Vet Clin 2011;28:6:617-620. Clyde VL, Orosz SE, Munson L. Severe hepatic fibrosis and bile duct hyperplasia in four amazon parrots. J Avian Med Surg 1996;10:252-257. Cullen JM, Stalker MJ. Liver and Biliary System. In: Jubb, Kennedy, Palmer's Pathology of Domestic Animals, Canada: Elsevier;2016:2:p.258-352. DOI:10.1016/B978-0-7020-5318-4.00008-5. Wheler CL, Webber RA. Localized ascites in a cockatiel (Nymphicus hollandicus) with hepatic cirrhosis. Journal of avian medicine and surgery, 2002;16:4:300-305. http://dx.doi.org/10.1647/1082-6742(2002)016[0300:LAIACN]2.0.CO;2. Jaensch S. Diagnosis of avian hepatic disease. Semin Avin Exotic Pet Med 2000;9:126-135. https://doi.org/10.1053/ax.2000.7140. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8124577","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":548378768,"identity":"ddfa6eef-38b0-4926-bad7-ca6b0f6f92cf","order_by":0,"name":"Erick Platini","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIie3QMWrDMBSA4ScKySLw+oTd9AoqgVDwkKtYS7P0AB5CUTGoS5quGUp7hUydCwJ50QE6ZLAJeE62TKWySaAEJe3YQT8IHg8+IQQQCv3LiCQSIGkHyHKI9usLADxPKPRaYoHJ30l3fUvaSf2BRLF+2C5gRaO3QlX1q8YoLusN5KmQ8VPlI2wuCraEhqIhj1y8a2TzuyGCnQiZlNxHuCWKVKApGKLQkXtuKSBRWki89T5sfCBXHXnROLb99Y58nSacOrJ0hHdEauQURkjkaYKWFGzBG3pthMLMTBAtHd24YagS4/+xWb/ezvLVYKDLhu2mKbrN+nMzTS+fY+Ul++d9HC0yd3pngOuYhEKhUOhH34m+Xa+zbhZ6AAAAAElFTkSuQmCC","orcid":"","institution":"Universidade Federal Rural do Semi-Árido","correspondingAuthor":true,"prefix":"","firstName":"Erick","middleName":"","lastName":"Platini","suffix":""},{"id":548378770,"identity":"6110d9cc-371d-4538-b5f7-1a3ab30676b1","order_by":1,"name":"Artefio Oliveira","email":"","orcid":"","institution":"Federal University of Campina Grande","correspondingAuthor":false,"prefix":"","firstName":"Artefio","middleName":"","lastName":"Oliveira","suffix":""},{"id":548378772,"identity":"d1280ca7-728c-4a1d-98bc-f3dac5c0709e","order_by":2,"name":"Débora Cardoso","email":"","orcid":"","institution":"Federal University of Campina Grande","correspondingAuthor":false,"prefix":"","firstName":"Débora","middleName":"","lastName":"Cardoso","suffix":""},{"id":548378774,"identity":"c19834bf-f729-419e-9d4c-53b23548f6b2","order_by":3,"name":"Glauco Galiza","email":"","orcid":"","institution":"Federal University of Campina Grande","correspondingAuthor":false,"prefix":"","firstName":"Glauco","middleName":"","lastName":"Galiza","suffix":""},{"id":548378775,"identity":"56e19fa7-3336-47f2-b968-3f4e6416791f","order_by":4,"name":"Antonio Dantas","email":"","orcid":"","institution":"Federal University of Campina Grande","correspondingAuthor":false,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Dantas","suffix":""}],"badges":[],"createdAt":"2025-11-16 01:08:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8124577/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8124577/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96805853,"identity":"83bf1199-9a62-4216-be3f-a0a75335e77e","added_by":"auto","created_at":"2025-11-26 09:12:12","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":117535,"visible":true,"origin":"","legend":"\u003cp\u003eHepatic cirrhosis in a cockatiel. A) Coelomic cavity containing clear, watery fluid (ascites) and a markedly shrunken liver. B) Liver diffusely reduced in size, with an irregular capsular surface and multifocal, well-defined nodules showing mottled green to yellow coloration.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8124577/v1/d77e828def80adf98b1d1490.jpg"},{"id":96805854,"identity":"3d27ec98-3230-4114-ae87-259b87d1b59f","added_by":"auto","created_at":"2025-11-26 09:12:12","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":531935,"visible":true,"origin":"","legend":"\u003cp\u003eHepatic cirrhosis in a cockatiel. A) Liver. Replacement of the hepatic parenchyma by extensive fibrous septa surrounding well-defined islands of hepatocytes (regenerative nodules). HE, obj. 5×. B) Liver, regenerative nodule. Hepatocytes exhibiting macro- and microvacuolar cytoplasmic degeneration. HE, obj. 20×. C) Liver, regenerative nodule. Areas of hepatocellular degeneration and necrosis. HE, obj. 40×. D) Liver. Numerous dark blue collagen strands encircling a regenerative nodule. MT, obj. 20×.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8124577/v1/5a31d072998847e42ba68f3f.jpg"},{"id":100949968,"identity":"bd04975d-007b-4072-8fa7-db79317e415d","added_by":"auto","created_at":"2026-01-23 07:06:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":930593,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8124577/v1/062777ff-3906-41ee-9dd2-f3d7211975be.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Hepatic cirrhosis in a cockatiel (Nymphicus hollandicus) from Brazil","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe avian liver is responsible for a wide range of metabolic activities, including the synthesis, storage, filtration, and excretion of several nutrients and chemical compounds (Grunkemeyer, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). Consequently, hepatic dysfunction is considered one of the most significant medical problems in birds (Hochleithner et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). Its causes include congenital, infectious, and non-infectious disorders (Schmidt et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNon-infectious hepatic diseases encompass lipidosis, hepatic atrophy, pigmentary hepatopathies, visceral urate deposition (gout), amyloidosis, lysosomal storage diseases, xanthomatosis, neoplasms, chronic-active hepatitis, and fibrosis (Schmidt et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Regardless of etiology, the liver has substantial functional reserve and regenerative capacity, and only lesions affecting most of the hepatic parenchyma are likely to produce clinical signs of liver failure (Hochleithner et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2006\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn general, destruction of the hepatic parenchyma triggers regeneration, biliary hyperplasia, and varying degrees of fibrosis (Hochleithner et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). Hepatic fibrosis is an uncommon histological finding in birds and often represents a nonspecific response to severe or repeated hepatic injury. Therefore, the present report details the clinical and anatomopathological features of end-stage liver disease in a cockatiel (\u003cem\u003eNymphicus hollandicus\u003c/em\u003e) from Brazil.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA 17-year-old male cockatiel (\u003cem\u003eNymphicus hollandicus\u003c/em\u003e) was presented with a one-week history of apathy, inappetence, weakness, and reluctance to move. The bird had been with the owner throughout its life and had no prior history of illness. Its diet consisted mainly of a commercial seed mixture (sunflower seeds, birdseed, and oats), supplemented occasionally with bread, green corn, and cabbage. Fresh water was offered ad libitum, and a vitamin complex was provided twice a year. The cockatiel died shortly after presentation and was submitted for necropsy.\u003c/p\u003e\u003cp\u003ePostmortem examination revealed an overweight body condition (90 g; body score 4/5). Significant gross findings included a clear, watery effusion within the coelomic cavity (ascites) and a markedly firm, shrunken liver with a diffusely irregular capsular surface. Multifocal, well-demarcated, mottled green-to-yellow nodules measuring up to 0.3 cm in diameter were scattered throughout the hepatic surface (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and B). On cut surface, these nodules were soft, compact, yellow to tan, and extended deeply into the parenchyma.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSamples of the skin, central nervous system, and organs of the coelomic cavity were fixed in 10% neutral buffered formalin, routinely processed for histology, embedded in paraffin wax, cut at 3 \u0026micro;m sections, and stained by hematoxylin and eosin (HE) and Masson's trichrome (MT).\u003c/p\u003e\u003cp\u003eHistopathological evaluation revealed that approximately 80% of the hepatic parenchyma was replaced by extensive fibrous septa, which surrounded well-defined islands of hepatocytes (regenerative nodules) and extended toward the remaining portal triads (bridging fibrosis) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and B). These fibrous tracts frequently contained moderate bile duct proliferation and mild, multifocal inflammatory infiltrates composed of lymphocytes, plasma cells, and occasional macrophages. Within the regenerative nodules, the residual hepatocytes displayed macro- and microvacuolar cytoplasmic degeneration, sometimes accompanied by individual or small clusters of necrotic hepatocytes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB and C). All other organs were unremarkable. The collagen strands within the fibrous septa were highlighted in dark blue in the MT-stained sections (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe diagnosis of hepatic cirrhosis was based on the clinical and anatomopathological findings. It seems to be a frequent condition in chronic liver diseases that the initial causative insults may precede any severe clinical signs and quickly disappear, which makes it very difficult to accurately identify the causes (Davies, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2000\u003c/span\u003e). However, the pathological findings of hepatic fibrosis with hepatocellular loss, bile duct hyperplasia, and multifocal chronic inflammation are suggestive of toxic hepatopathies (Lee et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2011\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe diagnosis of hepatic cirrhosis was based on the clinical and anatomopathological findings. In chronic liver diseases, the primary injurious events often occur long before severe clinical signs become evident and may subside quickly, making the precise identification of the underlying cause particularly challenging (Davies, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2000\u003c/span\u003e). Despite this limitation, the pathological features observed in this case, including marked hepatic fibrosis associated with hepatocellular loss, bile duct hyperplasia, and multifocal chronic inflammation, are compatible with the morphological patterns typically described in toxic hepatopathies (Lee et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). These alterations reflect a prolonged reparative response to hepatocellular injury, ultimately leading to distortion of the hepatic architecture and progression to cirrhosis.\u003c/p\u003e\u003cp\u003eToxic injury to the liver has been reported in mammals secondary to exposure to a wide range of harmful agents, including mycotoxins, heavy metals such as copper, iron, selenium, arsenic, and mercury, as well as various chemicals and organic compounds such as chloroform, chlordane, dieldrin, tannic acid, tetrachloroethane, dimethylnitrosamine, carbon tetrachloride, coal tar pitch, and gossypol. Similar lesions may also occur in association with nutritional deficiencies, particularly of methionine and choline (Clyde et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e1996\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCommon hepatotoxins in pet birds include mycotoxins such as aflatoxins and citrinin (Clyde et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e1996\u003c/span\u003e). Cockatiels, in particular, are highly sensitive to aflatoxins, and it has been proposed that chronic-active hepatitis in this species may arise from prior exposure to these toxins (Schmidt et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In this case, the toxic hepatopathy was likely caused by the daily seed mixture, which was possibly stored under improper conditions, allowing fungal proliferation and toxin production.\u003c/p\u003e\u003cp\u003eLiver disease in mammals disrupts several critical physiological processes and may manifest as hepatic encephalopathy, ascites, jaundice, hemorrhagic diathesis, hepatogenous photosensitization, hepatorenal syndrome, and hepatocutaneous syndrome (Cullen \u0026amp; Stalker, 2016). In birds, however, there are no pathognomonic clinical signs of hepatic dysfunction (Grunkemeyer, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2010\u003c/span\u003e). In this case, the cockatiel showed several nonspecific signs, including apathy, reduced appetite, and weakness. Ascites was present, although it was not clinically apparent. In addition, jaundice is not a typical manifestation of hepatic disease in birds because biliverdin, rather than bilirubin, is the predominant bile pigment (Hochleithner et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2006\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTherefore, the diagnosis of liver disease in avian species should rely on the integration of multiple diagnostic approaches, including physical examination, clinicopathologic testing, imaging studies, and, when feasible, hepatic biopsy (Grunkemeyer, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2010\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAmong the available laboratory tests, plasma bile acid measurement is considered a more accurate and specific prognostic indicator in cases of acute hepatitis (Lee et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). In the present case, no plasma biochemical analyses were performed. Nonetheless, it is important to note that in patients with end-stage liver disease, liver enzyme activities may be normal or even decreased, as active hepatocellular injury may no longer be occurring (Wheler \u0026amp; Webber, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2002\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eHepatic biopsy is often necessary for the definitive diagnosis and proper characterization of liver disease (Jaensch, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2000\u003c/span\u003e), as histopathological evaluation provides direct evidence of the severity and nature of the hepatic lesions. Biopsy samples can be obtained through blind or ultrasound-guided percutaneous techniques, endoscopic biopsy, or by performing a liver wedge biopsy during celiotomy (Lee et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2011\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAn interesting pathological finding was the partially mottled green appearance of the liver. As previously noted, biliverdin is the principal bile pigment in birds and is responsible for its characteristic green coloration (Hochleithner et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). In cases where the normal hepatic architecture is replaced by structurally abnormal nodules, bile flow becomes impaired (cholestasis), which can ultimately alter the coloration of the organ.\u003c/p\u003e\u003cp\u003eHistopathological examination revealed that most of the hepatic parenchyma had been replaced by fibrous tissue interspersed with regenerative nodules, while the limited remaining normal tissue contained degenerated and necrotic hepatocytes. Hepatic fibrosis represents a key stage in the progression of many liver diseases, and it is estimated that more than 80% of the liver must be affected before hepatic dysfunction becomes clinically apparent (Grunkemeyer, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2010\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDifferential diagnosis should include hepatic lipidosis, hepatic neoplasia, and bacterial, viral, or chlamydial hepatitis (Wheler \u0026amp; Webber, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). However, the histopathological findings in this case, marked by extensive fibrosis and only minimal inflammation, were sufficiently specific to establish the morphological diagnosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAlthough cirrhosis is an uncommon condition in birds, it should be considered among the differential diagnoses of chronic liver diseases. Unlike mammals, clinical signs in avian species are nonspecific, making the diagnosis of cirrhosis more challenging. Therefore, the use of multiple diagnostic methods is recommended, with anatomopathological evaluation providing the most reliable information regarding the characteristics and severity of the hepatic lesions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003cp\u003eNo ethical approval was required for this study, as this is a retrospective case report of a cockatiel referred for necropsy.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003cp\u003e Written informed consent has been obtained from the patient\u0026rsquo;s owner to publish this paper.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eNo funding was obtained for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eClinical examinations were performed by AMO and DFC. The writing of the manuscript was carried out by EPFS, GJNG and AFMD. Figure preparations were carried out by EPFS and AMO. All the authors have read and approved the submitted version.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNo datasets were generated or analysed during the current study\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGrunkemeyer VL. Advanced Diagnostic Approaches and Current Management of Avian Hepatic Disorders. Vet Clin North Am Exot Anim Pract 2010;13:3:413\u0026ndash;427. https://doi.org/10.1016/j.cvex.2010.05.005.\u003c/li\u003e\n\u003cli\u003eHochleithner M, Hochleithner C, Harrison LD. Evaluating and treating the liver. In: Harrison GJ, Lightfoot TL, editors. Clinical avian medicine, Palm Beach: Spix Publishing;2006,p.441-449. \u003c/li\u003e\n\u003cli\u003eSchmidt RE, Drury RR, Phalen DN. Pathology of pet and aviary birds. 2nd ed. John Wiley \u0026amp; Sons, Inc. Published, 2015. DOI:10.1002/9781118828007.\u003c/li\u003e\n\u003cli\u003eDavies RR. Avian Liver disease: etiology and pathogenesis. Semin Avian Exotic Pet Med 2000;3:115-125. https://doi.org/10.1053/ax.2000.7138.\u003c/li\u003e\n\u003cli\u003eLee SY, Kim DY, Park HM. Hepatic Fibrosis and Bile Duct Hyperplasia in a Young Orange Winged Amazon Parrot (Amazona amazonica). J Vet Clin 2011;28:6:617-620.\u003c/li\u003e\n\u003cli\u003eClyde VL, Orosz SE, Munson L. Severe hepatic fibrosis and bile duct hyperplasia in four amazon parrots. J Avian Med Surg 1996;10:252-257.\u003c/li\u003e\n\u003cli\u003eCullen JM, Stalker MJ. Liver and Biliary System. In: Jubb, Kennedy, Palmer\u0026apos;s Pathology of Domestic Animals, Canada: Elsevier;2016:2:p.258-352. DOI:10.1016/B978-0-7020-5318-4.00008-5.\u003c/li\u003e\n\u003cli\u003eWheler CL, Webber RA. Localized ascites in a cockatiel (Nymphicus hollandicus) with hepatic cirrhosis. Journal of avian medicine and surgery, 2002;16:4:300-305. http://dx.doi.org/10.1647/1082-6742(2002)016[0300:LAIACN]2.0.CO;2.\u003c/li\u003e\n\u003cli\u003eJaensch S. Diagnosis of avian hepatic disease. Semin Avin Exotic Pet Med 2000;9:126-135. https://doi.org/10.1053/ax.2000.7140.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Avian disease, hepatopathy, fibrosis, liver failure","lastPublishedDoi":"10.21203/rs.3.rs-8124577/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8124577/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA 17-year-old male cockatiel (\u003cem\u003eNymphicus hollandicus\u003c/em\u003e) was presented with a one-week history of apathy, inappetence, weakness, and reluctance to move, and died shortly afterward. Postmortem examination revealed an overweight body condition, ascites, and a markedly firm, shrunken liver with a diffusely irregular capsular surface and multifocal, well-defined green-to-yellow nodules. On cut surface, these nodules were soft, compact, yellow to tan, and extended deeply into the parenchyma. Histologically, the hepatic tissue was largely replaced by broad fibrous septa that enclosed distinct islands of hepatocytes forming regenerative nodules. Additional findings included bile duct hyperplasia and multifocal infiltrates of lymphocytes, plasma cells, and occasional macrophages. The remaining hepatocytes exhibited cytoplasmic degeneration or necrosis. Based on the clinical presentation and anatomopathological features, hepatic cirrhosis was diagnosed. Although considered uncommon in avian species, cirrhosis should be included in the differential diagnosis of chronic liver disorders, particularly in aged birds or those with a history suggesting prolonged hepatic injury.\u003c/p\u003e","manuscriptTitle":"Hepatic cirrhosis in a cockatiel (Nymphicus hollandicus) from Brazil","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-26 09:12:07","doi":"10.21203/rs.3.rs-8124577/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"32a1f1d5-d2d0-4fb7-95ff-cdbcde45962e","owner":[],"postedDate":"November 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-22T07:46:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-26 09:12:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8124577","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8124577","identity":"rs-8124577","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}