Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation

Kim, Chiwan; Aono, Shintaro; Marubashi, Shigeru; Wada, Hiroshi; Kobayashi, Shogo; Eguchi, Hidetoshi; Takeda, Yutaka; Tanemura, Masahiro; Okumura, Nobuaki; Takao, Toshifumi; Doki, Yuichiro; Mori, Masaki; Nagano, Hiroaki

doi:10.1016/j.jss.2011.02.044

Cited by 11 publications

(6 citation statements)

References 41 publications

(51 reference statements)

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“…Schmuck et al (27) CD44, CXCL19 ELISA -/45 ACR miR-122, miR-133a, miR-148a, and miR-194 qPCR Kim et al (28) APN Proteomics -/9 ACR Adams et al (29) ICAM1 ELISA -/61 ACR Adams et al (30) IL2R Unknown -/18 ACR Tono et al (31) IL6 ELISA 11/-ACR Umeshita et al (32) IL6 ELISA -/51 ACR Morimoto et al (33) CXCL10 ELISA -/41 ACR Ericzon et al (34) Bile acids ELISA -/10 Graft function CA/CDCA ratio HPLC Buis et al (35) Bile phospholipid/bile salt ratio ELISA, spectrophotometry -/111 NAS Chen et al (36) Bile salt/phospholipid ratio ELISA 90/-Bile duct injury/NAS Geuken et al (37) Bile salt/phospholipid ratio ELISA -/28 NAS ALP Spectrophotometry…”

Section: Rt-qpcrmentioning

confidence: 99%

“…The results generally show that biliary cytokines (eg, interleukin [IL] 2, IL6, and IL8 and chemokine [CXC] motif ligand [CXCL] 9 and CXCL10) reflect immunological activity within the liver more closely than serum factors. (26,(28)(29)(30)(31)(32) A study from 1989 already showed that biliary IL2 rose 24 hours before the onset of ACR and that biliary levels were more specific and sensitive than serum levels. (29) In a study on T tube bile collected from 51 LT recipients, biliary IL6 levels significantly increased with biopsy-proven ACR, and 70% of patients with ACR had high biliary IL6 levels.…”

Section: Bile Composition After Lt: Graft Function and Cellular Rejecmentioning

confidence: 99%

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Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

2020

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Bile secretion and composition reflects the functional status of hepatocytes and cholangiocytes. Bile composition can have a role in the assessment of donor grafts before implantation in the recipient. In addition, changes in bile composition after liver transplantation can serve as a diagnostic and prognostic tool to predict posttransplant complications, such as primary nonfunction, acute cellular rejection, or nonanastomotic biliary strictures. With the popularization of liver machine perfusion preservation in the clinical setting, there is a revisited interest in biliary biomarkers to assess graft viability before implantation. This review discusses current literature on biliary biomarkers that could predict or assess liver graft and bile duct viability. Bile composition offers an exciting and novel perspective in the search for reliable hepatocyte and cholangiocyte viability biomarkers.

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Section: Rt-qpcrmentioning

confidence: 99%

Section: Bile Composition After Lt: Graft Function and Cellular Rejecmentioning

confidence: 99%

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

2020

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“…13 We also revealed novel transcriptome patterns for ACR in recipients with HCV infection using liver biopsy samples. 11,34 Although liver biopsy is the standard for the diagnosis of transplant rejection, it is not easily repeated because of the invasiveness and risk of bleeding.…”

Section: Discussionmentioning

confidence: 89%

“…8–13 Because of the unstable and rapidly degradable nature of mRNA, proteomic analysis may have advantages in identifying a stable molecular diagnostic marker. Several studies have identified molecular markers in serum that predict ACR.…”

mentioning

confidence: 99%

Identification of Novel and Noninvasive Biomarkers of Acute Cellular Rejection After Liver Transplantation by Protein Microarray

Okubo¹,

Wada

Tanaka

et al. 2016

Transplantation Direct

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BackgroundAcute cellular rejection (ACR) is one of the main factors in transplanted organ failure in liver transplantation. A precise marker for diagnosing or predicting rejection is not currently available; therefore, invasive liver biopsy is standard procedure. To develop a noninvasive method for precise diagnosis of ACR, we evaluated autoantibodies from patient sera as potential biomarkers using protein microarrays (seromics).MethodsSera from hepatitis C virus–positive ACR patients were compared to three hepatitis C virus cirrhosis control groups and healthy volunteers. The control groups consisted of 2 no-ACR groups obtained on postoperative day 28 and 1 year after transplantation and a preoperative group obtained 1 day before transplantation. For validation, we evaluated whether the candidate antibodies can distinguish ACR from other types of liver dysfunction after liver transplantation using enzyme-linked immunosorbent assay.ResultsSeromic analysis by weighted average difference (WAD) ranking and Mann-Whitney U test revealed a significant increase of 57 autoantibodies in the sera of ACR patients with liver dysfunction. Among the 57 candidates, autoantibodies to charged multivesicular body protein 2B, potassium channel tetramerization domain containing 14, voltage gated subfamily A regulatory beta subunit 3, and triosephosphate isomerase 1 were regarded as potential biomarkers of ACR after liver transplantation. Using 20 ACR patients with variable backgrounds for validation, the autoantibodies to charged multivesicular body protein 2B and triosephosphate isomerase 1 were significantly increased in ACR patients compared to other control groups.ConclusionsA panel of autoantibodies identified by seromics as potential noninvasive biomarkers was clinically useful for diagnosing ACR after liver transplantation.

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“…On the other hand, another group could not find a relationship between ICAM‐1 and VCAM‐1 in bile and ACR. A Japanese group discovered (in a small group of five patients with biopsy‐proven ACR) a raise of alanine aminopeptidase N 3 days before the appearance of ACR . A major drawback in clinical practice is the bile collection that requires the position of a T tube.…”

Section: Acute Cellular Rejectionmentioning

confidence: 99%

Biomarkers for the diagnosis of acute cellular rejection in liver transplant recipients: A review

Verhelst

Troisi

Colle

et al. 2012

Hepatology Research

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The gold standard for the diagnosis of acute cellular rejection (ACR) is a liver biopsy. The quest for an alternative noninvasive biomarkers has been long and is ongoing. However, an efficient and useful biomarker has not been developed yet. In this manuscript, we review all possible candidate biomarkers that have been studied in recent years, starting with cytokines and ending with an overview of different newly discovered "omics". Promising paths are being explored but a valid non-invasive biomarker has not been discovered yet.

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Significance of Alanine Aminopeptidase N (APN) in Bile in the Diagnosis of Acute Cellular Rejection After Liver Transplantation

Cited by 11 publications

References 41 publications

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation

Identification of Novel and Noninvasive Biomarkers of Acute Cellular Rejection After Liver Transplantation by Protein Microarray

Biomarkers for the diagnosis of acute cellular rejection in liver transplant recipients: A review

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