Annals of Hepatology 8(1) 2009: 68-70
Annals of Hepatology 2009; 8(1): January-March: 68-70
Autoimmune hepatitis with giant-cell transformation
José Estradas;1 Virginia Pascual-Ramos;2 Braulio Martínez;3 Misael Uribe;1 Aldo Torre1
1Department of Gastroenterology.
2Department of Rheumatology and Immunology.
3Department of Pathology.
Instituto Nacional de Ciencias Médicas y Nutrición Salvador
Address for correspondence:
Aldo Torre, MD. M.Sc.
Instituto Nacional de Ciencias Médicas y Nutrición Salvador
Vasco de Quiroga 15, Section XVI, Tlalpan, Mexico City
Telephone: +55 5573 3418
Fax: +55 5655 0942
Manuscript received and accepted:
10 September and 27 November, 2008
Background/Aims: Giant-cell hepatitis (GCH), also
known as postinfantile or syncytial giant cell hepatitis,
is a frequent pattern of liver injury in the neonate, pri-
marily seen in the first three months of life. Few cases
in adults have been reported, some of them associated
to autoimmune diseases such as autoimmune hepatitis.
Methods: We present a case of autoimmune hepatitis
with giant cell transformation in a 39 year old male
with polyarthritis. We discuss his clinical presentation
and course. We made a review of the literature of
agents associated to this diagnosis, the mechanisms in-
volved in the formation of giant hepatocytes, the histo-
logical findings, clinical course, treatment options and
prognosis of this rare entity. Results and conclusions:
In conclusion, the clinical course varies from normal-
ization of hepatic histology to progression to cirrhosis
and liver failure. The prognosis is dictated by the un-
derlying liver disease and in the setting of autoimmune
hepatitis the clinical course is usually severe with most
of the patients progressing to cirrhosis. Prolonged
treatment with corticosteroids and immunosuppres-
sants is usually effective in rendering the cirrhosis in-
Key words: Autoimmune hepatitis, giant-cell hepatitis,
postinfantile giant cell hepatitis, syncytial giant cell
Giant-cell hepatitis (GCH), also known as postinfan-
tile or syncytial giant cell hepatitis, is a frequent pattern
of liver injury in the neonate, primarily seen in the first
three months of life. Few cases in adults have been re-
ported, some of them associated to autoimmune diseases
such as autoimmune hepatitis.
We herein present a case of autoimmune hepatitis with
giant cell transformation in a 39 year old male with pol-
yarthritis involving the shoulders, elbows, wrists, metac-
arpophalangeal and proximal interphalangeal joints,
knees, ankles and metatarsophalangeal joints. He had a 5
month history of asthenia, weight loss (20 kg), dry cough
and morning stiffness. He admitted taking non-steroidal
anti-inflammatory drugs (NSAIDs) for pain relief.
On physical examination the patient was found
cachectic with arthritis of the mentioned joints. Neither
hepatomegaly nor tenderness on the right upper quad-
rant was found on palpation.
Laboratory studies showed WBC 18.8 K/μL, hemo-
globin 12.1 g/dL, platelets 611 K/μL, ALT 74 U/L, AST
59 U/L, GGT 158 U/L, bilirubins were within normal lim-
its, alkaline phosphatase was of 226 U/L, albumin 2.76
g/dL, and globulines of 3.94.
The rheumatoid factor (nephelometry) was slightly
positive: 40.51 UI/mL, anti-cyclic citrullinated peptide
autoantibody (2nd generation ELISA) and antinuclear
antibodies (immunofluorescence) were both negative,
anti-neutrophil cytoplasmic autoantibodies (ANCAs)
(immunofluorescence) showed a c-ANCA pattern in a ti-
tle of 1:320 with negative myeloperoxidase and pro-
teinase-3 (ELISA). Serum levels of complement were de-
creased (C3 59.5 mg/dL, C4 9.0 mg/dL), the viral pro-
file was negative.
The chest X ray showed an apparent widening of the
mediastinum, a chest CT was performed and showed a
nodular lesion with central necrosis in the anterior me-
diastinum and mediastinal adenomegalies. The medi-
astinal mass was found to be an atypical thymoma
type B3 (World Health Organization Classification) af-
ter the surgical excision and pathological examina-
tion were performed, radiotherapy was indicated after-
He was started on chloroquine, sulfasalazine and pred-
nisone which relieved the rheumatologic symptoms, but
after 6 months of treatment he became jaundiced and had
J Estradas et al. Autoimmune hepatitis and giant-cell hepatitis
a progressive increment of bilirrubins (total bilirubins
11.2 mg/dL, direct bilirubins 6.4 mg/dL) and transami-
nases (ALT: 523 U/L, AST: 187 U/L) Serum globulines
were within normal range and anti-mitochondrial anti-
bodies were negative. Drug toxicity, biliary tract disease
and infectious causes were excluded.
A liver biopsy was performed and showed interface
hepatitis with mild portal and periportal lymphoplasma-
cytic inflammation, hepatocyte swelling and necrosis
(Figure 1). Giant multinucleated hepatocytes were
present in more than 50% of the biopsy, predominantly
in periportal area (Figure 2); other histological findings
were mild lobular inflammation, necrosis and mild inter-
laminar fibrosis. The diagnosis of autoimmune hepatitis
with giant cell transformation was concluded.
The final «Autoimmune Hepatitis Score» for the diag-
nosis of autoimmune hepatitis was: 20.1
He was started on prednisone 40 mg and azathioprine
100 mg daily, he has been attending our clinic for regu-
lar check-ups and his clinical and biochemical profile
have markedly improved after one year of treatment.
Giant cell hepatitis (GCH) is an infrequent presenta-
tion of liver injury in the adulthood. It is more common-
ly described in neonates as a response of immature hepa-
tocytes to a variety of insults such as cholestasis,2-4 and
when it occurs in adults, it is known as postinfantile giant
Agents that have been associated to this diagnosis in-
clude: infections such as hepatitis A, B and C viruses,6
HIV, EBV, and paramyxovirus;7 drugs as methotrexate, 6-
mercaptopurine, p-aminosalicylic acid, chlorpromazine,
vinyl chloride, clomethacin,2 and a case of GCH after a
human herpesvirus 6-induced adverse drug reaction has
also been described;8 diseases like sickle cell anemia, au-
toimmune hemolytic anemia, chronic lymphocytic leu-
kaemia,9 non-Hodgkin’s lymphoma involving the liver,4
polyarteritis nodosa,10 autoimmune hepatitis (type I and
II5,11), ulcerative colitis (suggesting that GCH may be in-
cluded in the list of hepatic complications of inflamma-
tory bowel disease),2,12 primary biliary cirrhosis13 and pri-
mary sclerosing cholangitis;3 congenital metabolic dis-
eases such as alpha 1-antitrypsin deficiency or
haemosiderosis, and in some other cases the etiology re-
Giant-cell transformation is a nonspecific reaction to
various stimuli rather than a specific disease process.4,14
There are two possible mechanisms in the formation of
giant hepatocytes: the fusion of individual cells to form
a syncytium (therefore the used term «syncytial giant cell
hepatitis»15) and the failure of the cytoplasm to divide at
the time of nuclear division.4,5,14
The diagnosis is made when multinucleated syncytial
hepatocytes are observed in liver biopsy,3 they may be
seen as isolated clusters of giant cells or multinucleated
giant cells over mononuclear hepatocytes, appearing pre-
dominantly in zone 3 or 1 of the Rappaport acinus. Other
histological findings include portal inflammation (more
commonly lymphocytic, but plasma cells and neutro-
phils can also be seen), varying degrees of acinar inflam-
mation, hepatocellular necrosis, ballooning degenera-
tion, bile duct lesions (nonsuppurative destructive cho-
langitis, periductal scarring, and ductopenia), periportal
fibrosis and cirrhosis.4
The clinical course may vary from normalization of
hepatic histology, either spontaneously or by medical
treatment, to progression to cirrhosis and liver failure.2,3
The prognosis is dictated by the underlying liver dis-
ease2,16 and in the setting of autoimmune hepatitis the
clinical course is usually severe with most of the patients
progressing to cirrhosis. Prolonged treatment with corti-
costeroids and immunosuppressants is usually effective
Figure 1. Microscopic view of the liver biopsy showing interface
hepatitis with mild portal and periportal lymphoplasmacytic infla-
mmation, hepatocytes swelling and necrosis.
Figure 2. Giant multinucleated hepatocytes in more than 50% of
the biopsy, predominantly in periportal area.
Annals of Hepatology 8(1) 2009: 68-70 70 Download full-text
ESTE DOCUMENTO ES ELABORADO POR MEDI-
in rendering the cirrhosis inactive.5 A reduction in the
number of giant hepatocytes after treatment of the au-
toimmune and cholestatic features has been reported pre-
viously, which may suggest that an autoimmune mecha-
nism as well as cholestasis may be involved in the patho-
genesis of giant cell transformation.2,3,5,17,18
Most of the patients with GCH have an unfavorable
prognosis, with a rapidly progressive course leading to
death or the need for orthotopic liver transplantation, al-
though GCH can recur in liver allograft.19,20
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