https://doi.org/10.1177/1066896918799941
International Journal of Surgical Pathology
1–5
© The Author(s) 2018
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DOI: 10.1177/1066896918799941
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Case Report
Introduction
Multidrug-resistant P-glycoprotein (MDR3) is a phospho-
lipid floppase involved in biliary excretion of phosphati-
dylcholine.
1
Defects in MDR3 protein impair biliary
phospholipid secretion, which is required for the formation
of mixed micelles in bile resulting in a variety of choles-
tatic syndromes ranging from progressive familial intrahe-
patic cholestasis (PFIC) type 3 in children to biliary
cirrhosis in adults.
2,3
Complete absence of canalicular
MDR3 immunostaining is diagnostic of MDR3 defi-
ciency.
4,5
We report 2 cases of MDR3 deficiency diagnosed
with complete absence of MDR3 immunostaining in
hepatic canaliculi who underwent living donor liver trans-
plantation (LT) at our center. Both the explants demon-
strated interlobular bile ducts loss. One of the patients also
underwent genetic studies demonstrating ABCB4 muta-
tion. The patients are on regular follow-up and are doing
well. Paucity of bile ducts encompasses numerous entities
resulting in bile duct injury, resulting in bile duct loss.
Rarely duct loss is described in MDR3 deficiency in adults.
6
Occasional older studies have described duct paucity in
PFIC; however, no further characterization or typing of
PFIC were done.
7
No definite description of paucity of
interlobular bile ducts in pediatric liver with MDR3 defi-
ciency is available in the literature. We describe the find-
ings in the present cases and discuss the various causes of
bile duct paucity in pediatric livers.
Case 1
A 7-year-old male child, first child of nonconsanguineous
parents, was referred for LT due to decompensated chronic
liver disease. The child initially presented with anorexia,
growth failure, and severe pruritus at the age of 2 years
without jaundice or pale stools. Blood tests showed ele-
vated aminotransferases, and sonography revealed liver
with altered echotexture. The child was on supportive
799941IJS XX X 10.1177/1066896918799941International Journal of Surgical PathologyVij et al
case-report 2018
1
Gleneagles Global Health City, Chennai, India
2
University of Kelaniya, Kelaniya, Sri Lanka
Corresponding Author:
Mukul Vij, Department of Pathology, Gleneagles Global Health City,
Perumbakkam, Chennai, Tamilnadu 600100, India.
Email: mukul.vij.path@gmail.com
Paucity of Interlobular Bile Ducts in
Multidrug-Resistant P-Glycoprotein 3
(MDR3) Deficiency
Mukul Vij, MD, PDCC
1
, Joseph Valamparampil, MD, DCH
1
,
Naresh Shanmugum, DCH, DNB, FRCPCH, CCT, CSST
1
,
Srinivas Mettu Reddy, MS, DNB, FRCS, PhD
1
,
Shaman Rajindrajith, MD, PhD
2
, and Mohamed Rela, MS, FRCS, DSc
1
Abstract
Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator encoded by the ABCB4 gene located on
chromosome 7. MDR3 mediates the translocation of phosphatidylcholine across the canalicular membrane of the
hepatocyte into bile. Severe MDR3 deficiency typically occurs during childhood with progressive cholestasis evolving
to cirrhosis and liver failure, requiring liver transplantation. In this article, we report 2 pediatric cases of severe MDR3
deficiency with paucity of interlobular bile ducts. Both underwent living donor liver transplantation at our center for
decompensated liver disease and portal hypertension. We diagnosed severe MDR3 deficiency in both the cases with
negative MDR3 immunostaining in the explanted liver. Genetic studies revealed homozygous deletion single base pair
deletion in exon 24 of the ABCB4 gene in the second child. The patients are on regular follow-up after liver transplant
and are doing well. Our report highlights that cholangiopathy in MDR3 deficiency can lead to ductopenia in pediatric
livers.
Keywords
liver, multidrug-resistant P-glycoprotein 3, paucity of bile ducts, cirrhosis, immunohistochemistry