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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 3  |  Page : 103-105

Hepatitis with Syncytial Giant Cells in an Elderly Man: A Rare Histopathological Entity


1 Department of Pathology, The Rotherham NHS Foundation Trust, Rotherham, United Kingdom
2 Department of Pathology, Jawaharlal Nehru Medical College, Faculty of Medicine, A.M.U., Aligarh, Uttar Pradesh, India

Date of Submission14-May-2022
Date of Decision04-Jun-2022
Date of Acceptance06-Jun-2022
Date of Web Publication05-Jul-2022

Correspondence Address:
Kafil Akhtar
Department of Pathology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ghep.ghep_15_22

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  Abstract 


Giant cell transformation of hepatocytes is a nonspecific tissue reaction in neonates that is rarely seen outside of infancy. In children, it is particularly striking in cholestatic disorders and is prominent in neonatal hepatitis. In older patients, the presence of numerous hepatocyte giant cells is termed adult or postinfantile giant cell hepatitis (PIGCH) or syncytial giant cell hepatitis. About 25.0% of reported patients with PIGCH remain stable or have a gradual resolution of the disease. Corticosteroid treatment results in improvement in some but not all patients, and in the setting of autoimmune hepatitis, the clinical course may be progressive. We present a rare case of adult giant cell syncytial hepatitis with associated steatosis in a 79-year-old male, who presented with complaints of abdominal fullness, nausea, loss of appetite, and jaundice for the past 1 month.

Keywords: Giant cells, hepatitis, histopathology, liver, syncytial


How to cite this article:
Abrari A, Kattu WP, Akhtar K. Hepatitis with Syncytial Giant Cells in an Elderly Man: A Rare Histopathological Entity. Gastroenterol Hepatol Endosc Pract 2022;2:103-5

How to cite this URL:
Abrari A, Kattu WP, Akhtar K. Hepatitis with Syncytial Giant Cells in an Elderly Man: A Rare Histopathological Entity. Gastroenterol Hepatol Endosc Pract [serial online] 2022 [cited 2022 Aug 14];2:103-5. Available from: http://www.ghepjournal.com/text.asp?2022/2/3/103/349948




  Introduction Top


Syncytial giant cell hepatitis, commonly occurs in the pediatric population and is uncommon in adults.[1] It is a condition characterized by inflammation and large multinucleated hepatocytes in the hepatic parenchyma. Giant cell transformation of hepatocytes along with extramedullary hematopoiesis is a common response in newborn liver diseases.[2]

The etiologies of giant cell hepatitis vary among the individuals, including medications such as methotrexate, amitriptyline, herbal medicines, and doxycycline, autoimmune disorders such as autoimmune hepatitis, systemic lupus erythematosus (SLE), rheumatoid arthritis, and primary sclerosing cholangitis, as well as the infection with viruses such as hepatitis A, B, C, and E viruses, Epstein–Barr virus (EBV), human immunodeficiency virus (HIV), cytomegalovirus (CMV), and paramyxovirus.[3]

The clinical outcome of patients depends on the underlying etiology and varies from normalization of liver histology to progression to cirrhosis or even fulminant hepatitis.[4] Its incidence is very rare in adults (0.1%–0.25% of all liver diseases) and generally termed postinfantile giant cell hepatitis (PIGCH) or syncytial giant cell hepatitis.[5]

The diagnosis of syncytial giant cell hepatitis is made when hepatocellular multinucleated giant cells are found on liver biopsy.[6] The natural course is usually a fulminant, progressive course to cirrhosis within months, leading to death, or a requirement for transplantation.[7]


  Case Report Top


A 79-year-old man presented to the surgical outpatient department with complaints of abdominal fullness, nausea, loss of appetite, and jaundice for the past 1 month. There was no history of fever, hemoptysis, hematemesis, or weight loss. He had no history of alcohol consumption or blood transfusion. Although he had a history of angina pectoris and had been administered several drugs for these disorders, his condition had been stable for several years, and his drugs had not been changed. No history of any surgeries or any similar illness in the family was noted. There was no history of intake of drugs such as methotrexate, amitriptyline, herbal medicines, and doxycycline.

On physical examination, he had icterus and pedal edema. On systemic examination, per abdomen showed ascites and the liver was palpable 1 cm below the costal margin.

Complete blood count showed mild anemia with hemoglobin of 9 g/dl. Liver function tests (LFT) performed at admission showed serum aspartate aminotransferase level of 424 U/L, alanine aminotransferase level of 589 U/L, γ-glutamyl transpeptidase level of 281 U/L, alkaline phosphatase level of 617 U/L, and total bilirubin level of 1.7 mg/dL. A repeat LFT after a week of admission also showed all deranged parameters. Serology was negative for immunoglobulin M antibodies to hepatitis A virus, hepatitis B virus, hepatitis C virus, HIV, CMV, and EBV. Antinuclear antibody test for SLE and rheumatoid factor test for rheumatoid arthritis were negative. The etiological workup for Wilson's disease, hemochromatosis, and autoimmune hepatitis was negative.

Abdominal ultrasound and computed tomography scan showed ascites and mild hepatomegaly with morphological abnormalities including steatosis and shear wave elastography suggested mild hepatic fibrosis.

Due to the progressive nature of the disease, a needle biopsy was performed. Sections from submitted liver biopsy represented approximately 10 portal areas and the associated hepatic parenchyma. A mild disarray of lobulo portal relationships, with focal zone 3 intrahepatocytic cholestasis and numerous randomly scattered hepatocytes with mild anisonucleosis with several binucleate and multinucleated cells were noted. Spotty hepatocyte dropouts were noticed [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Canalicular biliary plugs were not prominent and bile lakes were not noticed. Macrovesicular steatosis was seen in up to 60.0% of the hepatocytes and foci of active lobular inflammation with a sprinkling of neutrophils and several multinucleated giant cells were evident. The portal areas showed mild inflammatory infiltrate, with lymphocytes and a few plasma cells [Figure 2]a, [Figure 2], [Figure 2]c. Acute cholangitis and bile duct damage were not seen. The fibrous tissue in portal areas was mildly increased and on reticulin staining appeared to attempt early extension of slender reticulin fibrils, beyond portal areas [Figure 2]d. Morphology was consistent with adult giant cell syncytial hepatitis and associated steatosis.
Figure 1: (a-d) Section shows hepatic parenchyma, with mild disarray of lobulo-portal relationships, with focal zone 3 intrahepatocytic cholestasis and numerous randomly scattered hepatocytes with mild anisonucleosis with several binucleate and multinucleated cells with spotty hepatocyte dropouts. H and E, various magnifications. Clockwise

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Figure 2: (a-d) Tissue section shows macrovesicular steatosis in up to 60.0% of the hepatocytes and foci of active lobular inflammation with a sprinkling of neutrophils and several multinucleated giant cells. The portal areas show a mild inflammatory infiltrate, with lymphocytes, and a few plasma cells. H and E × 40. (d) The fibrous tissue in portal areas is mildly increased and on reticulin staining appears to attempt early extension of slender reticulin fibrils, beyond portal areas. Reticulin × 40

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Our patient was prescribed ursodeoxycholic acid 750 mg/day along with high-caloric diet with adequate nutrition and was monitored clinically every day during hospitalization. After 2 weeks of admission, he showed clinical improvement with mild decrease in liver enzyme parameters. On regular follow-up at 3 months, he is fine with totally normal LFT.


  Discussion Top


Syncytial giant cell hepatitis is often seen in neonates but is uncommon in adults.[8] This condition is characterized by acute or chronic hepatitis and patients often show fulminant hepatitis, leading to liver failure.[9]

In many cases, the actual etiology is unknown, but there seems to be associations with various viral infections (particularly paramyxovirus), autoimmune disorders, drug toxicity, or herbal remedy.[10] Although the mechanism of development in adults has not been fully clarified. Syncytial giant cell is best regarded as an idiosyncratic response of regenerative or degenerative hepatocytes to noxious stimuli.[11] The most common causes of PIGCH are viral pathogens, drug toxicity, autoimmune disorders, and a combination of these factors, however, various other causes include posttransplantation status, malignancy, metabolic disease, and others.[2],[12]

Giant cell transformation of hepatocytes is a nonspecific tissue reaction in neonates that is rarely seen outside of infancy. In children, it is particularly striking in cholestatic disorders and is prominent in neonatal hepatitis. In older patients, the presence of numerous hepatocyte giant cells is termed adult or PIGCH or syncytial giant cell hepatitis.[2],[3]

This pattern of injury is seen in autoimmune liver disease and drug reactions, and is occasionally reported in HIV, hepatitis C, and hepatitis B infections. Some cases of adult giant cell hepatitis do not have a clearly established etiology and are regarded as idiopathic. In one series, 40.0% of patients had evidence of autoimmune diseases such as positive antinuclear antibodies or smooth muscle antibodies – this becomes significant in those cases where pathognomonic findings of autoimmune hepatitis are not evident.[1] Two major hypotheses regarding giant multinucleated cell development include (i) nuclear proliferation without cytoplasmic hepatocyte division and (ii) cytoplasmic fusion of several nonnuclear hepatocytes exposed to noxious stimuli.[4],[13] Subsequent fusion of these proliferated hepatocytes may be responsible for giant hepatocyte formation.[14] In our case, histological examination showed multinucleated syncytial giant cells with 3–5 nuclei in the periportal hepatic parenchyma and minimal centrilobular microvesicular fatty changes (steatosis).

About 25.0% of reported patients with PIGCH remain stable or have a gradual resolution of the disease.[15] Corticosteroid treatment results in improvement in some but not all patients, and in the setting of autoimmune hepatitis the clinical course may be progressive.[16],[17] Immunosuppressive drugs and antiviral treatments have shown limited success in the treatment of adult giant cell hepatitis, and orthotopic liver transplantation has been reported to be the only therapeutic option.[18],[19] Although no definitive benefit of immunosuppressive treatment has been shown in previous case reports due to the small sample sizes, active immunosuppressive treatment may be beneficial to suppress hepatocyte damage.[19]

Typically, giant cell hepatitis shows an overwhelming presence of giant cells on liver biopsy. In this patient, there were giant cells, but their presence in the biopsy was not overwhelming. This observation in this liver biopsy is puzzling, but should probably be considered a pointer to occult viral or other etiologies.

To conclude, the present case may suggest a subtype of PIGCH characterized primarily by insidious disease onset and progression, with syncytial giant cell development despite mild underlying active hepatitis and steatosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Devaney K, Goodman ZD, Ishak KG. Post-infantile giant-cell transformation in hepatitis. Hepatology 1992;16:327-33.  Back to cited text no. 1
    
2.
Fraquelli M, Colli A, Cocciolo M, Conte D. Adult syncytial giant cell chronic hepatitis due to herbal remedy. J Hepatol 2000;33:505-8.  Back to cited text no. 2
    
3.
Bihari C, Rastogi A, Sarin SK. Postinfantile giant cell hepatitis: An etiological and prognostic perspective. Hepat Res Treat 2013;2013:601290.  Back to cited text no. 3
    
4.
Gupta N, Njei B. Syncytial giant cell hepatitis in a patient with chronic lymphocytic leukemia. J Dig Dis 2015;16:683-8.  Back to cited text no. 4
    
5.
Arvaniti P, Zachou K, Koukoulis GK, Dalekos GN. Post-infantile giant cell hepatitis with features of acute severe autoimmune hepatitis probably triggered by diclofenac in a patient with primary myelofibrosis. Case Reports Hepatol 2018;2018:9793868.  Back to cited text no. 5
    
6.
Hartl J, Buettner R, Rockmann F, Farkas S, Holstege A, Vogel C, et al. Giant cell hepatitis: An unusual cause of fulminant liver failure. Z Gastroenterol 2010;48:1293-6.  Back to cited text no. 6
    
7.
Shah JA, Steinbrecher UP, Erb SR, Tha SP, Yoshida EM. Recurrent giant cell hepatitis in an 18 year old liver transplant patient. Ann Hepatol 2008;7:257.  Back to cited text no. 7
    
8.
Bassem M, Ricardo C, Mordechai R, Marta M, Shahid M. Post-infantile giant cell hepatitis: A single center's experience over 25 years. World J Hepatol 2019;11:752-60.  Back to cited text no. 8
    
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Kryczka W, Walewska-Zielecka B, Dutkiewicz E. Acute seronegative hepatitis C manifesting itself as adult giant cell hepatitis – A case report and review of literature. Med Sci Monit 2003;9 Suppl 3:29-31.  Back to cited text no. 9
    
10.
Tajiri K, Shimizu Y, Tokimitsu Y, Tsuneyama K, Sugiyama T. An elderly man with syncytial giant cell hepatitis successfully treated by immunosuppressants. Intern Med 2012;51:2141-4.  Back to cited text no. 10
    
11.
Ben-Ari Z, Broida E, Monselise Y, Kazatsker A, Baruch J, Pappo O, et al. Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as sub-fulminant hepatitis. Am J Gastroenterol 2000;95:799-801.  Back to cited text no. 11
    
12.
Ishikawa T. Diagnosis and treatment strategy for syncytial giant cell hepatitis. Intern Med 2012;51:2075-6.  Back to cited text no. 12
    
13.
Ahmed K, Zucker SD. Giant cell hepatitis in a teenage woman. Clin Gastroenterol Hepatol 2008;6:26-9.  Back to cited text no. 13
    
14.
Welte S, Gagesch M, Weber A, Longerich T, Millonig G. Fulminant liver failure in Wilson's disease with histologic features of postinfantile giant cell hepatitis; cytomegalovirus as the trigger for both? Eur J Gastroenterol Hepatol 2012;24:328-31.  Back to cited text no. 14
    
15.
Hayashi H, Narita R, Hiura M, Abe S, Tabaru A, Tanimoto A, et al. A case of adult autoimmune hepatitis with histological features of giant cell hepatitis. Intern Med 2011;50:315-9.  Back to cited text no. 15
    
16.
Potenza L, Luppi M, Barozzi P, Rossi G, Cocchi S, Codeluppi M, et al. HHV-6A in syncytial giant-cell hepatitis. N Engl J Med 2008;359:593-602.  Back to cited text no. 16
    
17.
Labowitz J, Finklestein S, Rabinovitz M. Postinfantile giant cell hepatitis complicating ulcerative colitis: A case report and review of the literature. Am J Gastroenterol 2001;96:1274-7.  Back to cited text no. 17
    
18.
Estradas J, Pascual-Ramos V, Martínez B, Uribe M, Torre A. Autoimmune hepatitis with giant-cell transformation. Ann Hepatol 2009;8:68-70.  Back to cited text no. 18
    
19.
Moreno A, Moreno A, Pérez-Elías MJ, Quereda C, Fernández-Muñoz R, Antela A, et al. Syncytial giant cell hepatitis in human immunodeficiency virus-infected patients with chronic hepatitis C: 2 cases and review of the literature. Hum Pathol 2006;37:1344-9.  Back to cited text no. 19
    


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