A case of primary biliary cirrhosis associated with pernicious anemia: a case report.

Abstract

Primary biliary cirrhosis is often associated with autoimmune diseases. However, its association with pernicious anemia has rarely been reported.We report a case of a 68-year-old woman who presented jaundice and pruritus. Mildly elevated serum levels of alkaline phosphatase and gamma-glutamyl transpeptidase were detected. The titer of anti-mitochondrial M(2 )anti-body was elevated. Histology of liver biopsy showed features of primary biliary cirrhosis. In addition, aregenerative macrocytic anemia was found in the full blood count. The diagnosis of pernicious anemia was established by megaloblastosis in bone marrow, atrophic gastritis without Helicobacter pylori, low level of vitamin B(12 )and good response to treatment regimen of vitamin B(12). The association of primary biliary cirrhosis and pernicious anemia is unlikely to be casual and may be explained by autoimmune mechanism commonly shared by the diseases.

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CASE REPORTOpen Access
A case of primary biliary cirrhosis associated with
pernicious anemia: a case report
Elhem Ben Jazia1*, Mabrouk Khalifa1, Atef Ben Abdelkader2, Naoufel Kaabia1, Neirouz Ghannouchi1,
Ahlem Braham1, Amel Letaief1, Fethi Bahri1
Abstract
Primary biliary cirrhosis is often associated with autoimmune diseases. However, its association with pernicious ane-
mia has rarely been reported.
We report a case of a 68-year-old woman who presented jaundice and pruritus. Mildly elevated serum levels of
alkaline phosphatase and g-glutamyl transpeptidase were detected. The titer of anti-mitochondrial M2anti-body
was elevated. Histology of liver biopsy showed features of primary biliary cirrhosis. In addition, aregenerative
macrocytic anemia was found in the full blood count. The diagnosis of pernicious anemia was established by
megaloblastosis in bone marrow, atrophic gastritis without Helicobacter pylori, low level of vitamin B12and good
response to treatment regimen of vitamin B12. The association of primary biliary cirrhosis and pernicious anemia is
unlikely to be casual and may be explained by autoimmune mechanism commonly shared by the diseases.
Introduction
Primary biliary cirrhosis (PBC) is a chronic autoimmune
liver disease of unknown aetiology. It’s characterized his-
tologically by chronic non suppurative destruction of
interlobular bile ducts leading to advanced fibrosis, cir-
rhosis and liver failure [1].
This disease may be associated with various autoim-
mune disorders, and a link with pernicous anemia (PA)
has seldom been described [2].
Case report
A 68-year-old woman was admitted in December 1999
to our department for jaundice, fatigue and pruritus.
Her previous medical history was unremarkable. There
was no history of alcohol, drug abuse, or family history
of liver disease. Physical examination revealed hepato-
megaly and splenomegaly. Her skin and sclerae were
icteric. There was no cutaneous xanthoma and no spider
angioma. Hepatic laboratory investigations found a cho-
lestatic alkaline phosphatase: 4950 UI/l (N: 40 UI/l), g-
glutamyl transpeptidase: 108 IU/l (N < 50 IU/l), direct
bilirubin level: 75 μmol/l (N < 5 μmol/l). The serum
concentration of total cholesterol, albumin, and
immunoglobulin, especially IgM level were within the
normal range, the prothrombin time was normal.
The full blood count revealed macrocytic aregenera-
tive anemia; hemoglobin 10 g/dl, mean corpuscular
volume (MCV) value of 124 fl, absolute reticulocyte was
60 × 103/mm3. Serum vitamin B12level was decreased
at 60 pg/ml. Viral serologic tests of hepatitis B and C
were both negative. Antinuclear antibodies and anti
smooth muscle antibody were negative. Whereas anti
mitochondrial antibody was positive at 1/400 by immu-
nofluorescence. Furthermore, anti parietal cell antibody
(PCA) and anti intrinsic factor antibody were negative.
Abdominal ultrasound examination showed hepato-sple-
nomegaly without other signs of portal hypertension
and excluded extra hepatic biliary obstruction.
Histological examination of a liver biopsy revealed a
portal inflammatory infiltrate mainly composed of lym-
phocytes invading and destroying the epithelium of bile
ducts. Inflammatory cells also extend to the peri-portal
areas (Fig. 1). Elsewhere, there was fibrosis peri-portal
without regenerative nodules. The bone marrow biopsy
showed megaloblastosis. Upper gastro intestinal endo-
scopy exhibited an atrophy of the gastric mucosa in the
body of the stomach. Gastric biopsy specimens showed
chronic inflammatory infiltrate into the lamina propria
associated with destruction of parietal cells and foci of
* Correspondence: elhem.benjazia@rns.tn
1Department of Internal Medicine and Infectious diseases, University Hospital
F Hached,4000, Sousse, Tunisia
Jazia et al. Cases Journal 2010, 3:11
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intestinal metaplasia and glandular atrophy. No Helico-
bacter pylori was seen
The diagnosis of PBC and Pernicious anemia was
made. The patient was treated by ursodeoxycholic acid
(UDCA = 800 mg/day) and intramuscular injection of
vitamin B12. After 3 months of treatment, a significant
improvement of laboratory data was established. In fact,
hemoglobin levels increased to 11,8 g/dl and MCV
decreased to 86 fl. Serum bilirubin gradually decreased,
alkaline phosphatase and g-glutamyl transpeptidase were
normalized. Biliary enzyme, albumin concentration and
prothrombin time remained within the normal range
during the following four years under UDCA and Vita-
min B12. Her hemoglobin rose to 13 g/dl.
Discussion
PBC is a rare chronic cholestatic liver disease most often
diagnosed in middle-aged women. It is characterized by
a destruction of the bile ducts, portal inflammation
causing hepatocyte destruction and extensive fibrosis.
Ultimately, liver cirrhosis and liver failure ensue [1].
PBC is quite rare in Tunisia, the prevalence and inci-
dence is unclear, because few epidemiologic studies have
been established. In our patient, the diagnosis of PBC
was confirmed on the basis of laboratory findings, posi-
tive anti mitochondrial antibody and histopathological
findings compatible with PBC on liver biopsy.
PBC is well known to be associated with auto immune
disorders including Sjögren’s syndrome, rheumatoid
arthritis, chronic thyroiditis and scleroderma. However,
few cases of PBC associated with PA have been
reported. The different cases reported in the literature
are represented in table 1.
Pernicious anemia is the end stage of atrophic gastritis
(type A gastritis) which results in the loss of parietal
cells in the fundus and body of the stomach. Loss of
parietal cells is associated with the failure of intrinsic
factor production and results in vitamin B12deficiency
and megaloblastic anemia [3]. The presence of mono-
nuclear cell infiltration into the gastric mucosa, parietal
cell antibody (PCA) and anti-intrinsic factor antibody
were in favour of the autoimmune basis for the gastritis
[2]. Although, they were negative in our patient, the
diagnosis of PA was established by macrocytic anemia
in peripheral blood, megaloblastosis in bone marrow,
atrophic gastritis without Helicobacter pylori, low serum
vitamin B12concentration and good response to treat-
ment using vitamin B12.
Some authors have reported that PCA are frequently
detected in patients with PBC[4] Oya et al. demon-
strated that severe and extensive gastric mucosal atro-
phy was manifested in patient with PBC, which
exhibited positive PCA [4]. On the other hand, Wirth
reported that none of the patients with PBC and PCA
had associated PA. Moreover, Floreani demonstrated
Figure 1 HE stain × 400: portal infiltrate composed of lymphocytes invading the bile duct epithelium (Arrow) and extension to the
peri portal areas (Head of arrow).
Jazia et al. Cases Journal 2010, 3:11
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that the prevalence of chronic atrophic gastritis is simi-
lar in PBC and dyspeptic controls [5]. This data sup-
ported that the presence of atrophic gastritis in PBC
remains a controversial subject. Tissue damage in
patients with PBC may be present in the salivary glands
and lacrymal glands, as well as other exocrine glands.
This is known as dry glands syndrome which results
from damage to the ductular epithelia by a common
autoimmune mechanism. The stomach also has an exo-
crine glandular structure. It’s possible that atrophic gas-
tritis is part of the dry-gland syndrome [6,7].
In conclusion, although PBC may occur in patients
affected by another immuno-mediated disorder, its
coexistence with PA is not frequently described. This
association does not seem casual and may be pathogeni-
cally explained by autoimmune mechanism that they
have in common.
Consent
Written informed consent was obtained from the patient
for publication of this case report and accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
Author details
1Department of Internal Medicine and Infectious diseases, University Hospital
F Hached,4000, Sousse, Tunisia.2Department of Anatomical Pathology,
University Hospital F Hached, 4000, Sousse, Tunisia.
Authors’ contributions
EBJ, MK: contributed equally to this work
ABA, NK: designed research
NG, Ahlem Braham, AL, FB: performed research
All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 26 September 2009
Accepted: 8 January 2010 Published: 8 January 2010
References
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2.Aoyama H, Sakugawa H, Nakasone H, Nakayoshi T, Kinijo A, Tamayose M,
et al: A rare association of primary biliary cirrhosis and pernicious
anemia. J Gastroenterol 2002, 37:560-3.
3. Takahashi T, Honma T, Ishizuka K, Fuse I, Asakura H: A female with
asymptomatic primary biliary cirrhosis associated with pernicious
anemia. J Gastroenterol Hepatol 2001, 16:1420-4.
4.Oya H, Uchida Y, Morshed SA, Nishioka M: Anti-parietal cell antibody in
autoimmune liver diseases is associated with gastric mucosal atrophy
and intestinal metaplasia. Adv Exp Med Biol 1995, 371:1087-9.
5.Floreani A, Biagini MR, Zappala F, Farinati F, Plebani M, Rugge M, et al:
Chronic atrophic gastritis and Helicobacter pylori infection in primary
biliary cirrhosis: a cross-sectional study with matching. Ital J Gastroenterol
Hepatol 1997, 29:13-7.
6.Epstein O, Thomas HC, Sherlock S: Primary biliary cirrhosis is a dry gland
syndrome with features of chronic graft-versus-host disease. Lancet 1980,
31:166-8.
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doi:10.1186/1757-1626-3-11
Cite this article as: Jazia et al.: A case of primary biliary cirrhosis
associated with pernicious anemia: a case report. Cases Journal 2010
3:11.
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Table 1 Characteristic of cases reported in the literature about association of primary biliary cirrhosis and pernicious
anemia
Aoyama HRenoux M
Number of case1 Obs.1
reference27
Age 59 68
genderwomanwoman
Hepatic laboratorycholestasischolestasis
Anti-mitochondrial
antibody
Histological finding of
liver biopsyand the scanty bile ductsand ductopenia
Macrocytic anemia yesyes
Serum vitamin B12
lowlow
Anti-parietal cell
antibody
Obs.2Obs.3 Obs.4
46
woman
cholestasis
positive
66
woman
cholestasis
positive
72
woman
cholestasis
positivepositivepositive
Espanded portal areas with fibrosisExtended fibrosis portalExtended fibrosis portal
and ductopenia
yes
low
-
Extended
fibrosis portal
yes
low
negative
No
mentioned
yes
low
-positive negative
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