Ann Surg Treat Res.  2018 Nov;95(5):249-257. 10.4174/astr.2018.95.5.249.

Alteration of MRP2 expression and the graft outcome after liver transplantation

• Yi NJ
• Kim J
• Choi Y
• Kim H
• Lee KB
• Jang JJ
• Lee JY
• Lee JM
• Han JK
• Lee KW
• Suh KS

• KMID: 2422934
• DOI: http://doi.org/10.4174/astr.2018.95.5.249

Abstract

PURPOSE
Multidrug resistance-associated protein (MRP) 2 is a glutathione conjugate in the canalicular membrane of hepatocytes. Early graft damage after liver transplantation (LT) can result in alteration of MRP2 expression. The purpose of this study was to evaluate the relationship between the pattern of MRP2 alteration and graft outcome.
METHODS
Forty-one paraffin-embedded liver graft tissues obtained by protocol biopsy within 2 months after LT; these were stained using monoclonal antibodies of MRP2. We selected 15 live donor biopsy samples as a control, that showed homogenous canalicular staining for MRP2. The pattern of canalicular MRP2 staining of graft was classified into 3 types: homogenous (type C0), focal (type C1), and no (type C2,) staining of the canaliculi.
RESULTS
In total, 17.1% graft tissues were type C0, 36.6% were type C1, and 46.3% were type C2. The median operation time was longer in patients with type C2 (562.6 minutes) than in patients with type C0 (393.8 minutes) (P = 0.038). The rates of posttransplant complications were higher in patients with type C2 (100%) than in patients with type C0 (42.9%) and C1 (73.3%) (P < 0.001).
CONCLUSION
MRP2 expression pattern was altered in 82.9% after LT. The pattern of MRP2 alteration was associated with longer operation time and higher rates of post-LT complications.

Keyword

Multidrug resistance-associated protein; Liver transplantation

MeSH Terms

Antibodies, Monoclonal
Biopsy
Glutathione
Hepatocytes
Humans
Liver Transplantation*
Liver*
Membranes
Multidrug Resistance-Associated Proteins
Tissue Donors
Transplants*
Antibodies, Monoclonal
Glutathione
Multidrug Resistance-Associated Proteins

Figure

• 

  Fig. 1 Multidrug resistance-associated protein 2 (MRP2) staining pattern in the liver. (A) Normal MRP2 staining pattern in the donor was homogenous canalicular staining, but there was no membranous staining of the cytoplasm. (B–D) The overall expression pattern of MRP2 in the recipient group showed alterations in 82.9% of the recipients. (A) Normal MRP2 staining pattern in the live liver donor (×400). (B) Type C0 (n = 7, normal, ×400); the pattern of homogenous canalicular staining similar to the normal donor liver. (C) Type C1 (n = 15, borderline, ×400); the alteration of expression pattern of MRP2 with focal canalicular and partial membranous staining. (D) Type C2 (n = 19, abnormal, ×400); the alteration of expression pattern of MRP2 with no canalicular staining but membranous staining.

• 

  Fig. 2 Changes in liver function test results according to the time flow among 3 groups. (A) AST, (B) ALT, (C) total billirubin, (D) gamma-glutamyl transpeptidase (GGT), and (E) ALP. Type C0, normal; type C1, borderline; type C2, abnormal.

• 

  Fig. 3 The cumulative risk of posttransplantation complications after protocol biopsy of the graft. Type C0, normal; type C1, borderline; type C2, abnormal.

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