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疾病鉴别生物标志物:丙型肝炎病毒复发与急性细胞排斥反应

Biomarkers of disease differentiation: HCV recurrence versus acute cellular rejection.

作者信息

Gehrau Ricardo, Mas Valeria, Archer Kellie, Maluf Daniel

机构信息

University of Virginia, Department of Surgery, Transplant Division, P.O. Box 800625, 904 Lane Rd, Charlottesville, VA, 22908-0625, USA.

Virginia Commonwealth University, Department of Biostatistics P.O. Box 980032, 730 East Broad Street, Room 3006, Richmond, VA 23298-0032, USA.

出版信息

Fibrogenesis Tissue Repair. 2012 Jun 6;5(Suppl 1):S11. doi: 10.1186/1755-1536-5-S1-S11. eCollection 2012.

DOI:10.1186/1755-1536-5-S1-S11
PMID:23259646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3368799/
Abstract

The wound-healing process induced by chronic hepatitis C virus (HCV) infection triggers liver damage characterized by fibrosis development and finally cirrhosis. Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease. However, acute cellular rejection (ACR) and HCV recurrence disease represent two devastating complications post-LT. The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists. Moreover, the HCV recurrence disease severity is highly variable post-LT. HCV recurrence disease progression is characterized by an accelerated fibrogenesis process, and almost 30% of those patients develop cirrhosis at 5-years of follow-up. Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process. In the present manuscript, the utility of microarray technology is applied for the ACR and HCV-recurrence biological characterization in post-LT liver biopsy samples. Moreover, WGE analysis was performed to identify predictive biomarkers of HCV recurrence severity in formalin-fixed paraffin-embedded liver biopsies prospectively collected.

摘要

慢性丙型肝炎病毒(HCV)感染引发的伤口愈合过程会导致以纤维化发展及最终肝硬化为特征的肝损伤。肝移植(LT)是终末期肝病HCV肝硬化患者的最佳外科治疗方法。然而,急性细胞排斥反应(ACR)和HCV复发疾病是肝移植术后两种极具破坏性的并发症。准确鉴别这两种情况对于治疗选择至关重要,而相似的组织学特征对病理学家来说是一项挑战。此外,肝移植术后HCV复发疾病的严重程度差异很大。HCV复发疾病的进展以加速的纤维化过程为特征,在随访5年时,近30%的患者会发展为肝硬化。通过定义明确的寡核苷酸微阵列平台进行全基因组基因表达(WGE)分析是对生物过程进行分子表征的有力工具。在本论文中,微阵列技术被用于肝移植术后肝活检样本中ACR和HCV复发的生物学特征分析。此外,还进行了WGE分析,以确定在福尔马林固定石蜡包埋的前瞻性收集的肝活检样本中HCV复发严重程度的预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/5de376ecf27f/1755-1536-5-S1-S11-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/ec153e3d2577/1755-1536-5-S1-S11-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/d2cd07a19932/1755-1536-5-S1-S11-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/53ac03ede912/1755-1536-5-S1-S11-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/5de376ecf27f/1755-1536-5-S1-S11-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/ec153e3d2577/1755-1536-5-S1-S11-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/d2cd07a19932/1755-1536-5-S1-S11-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/53ac03ede912/1755-1536-5-S1-S11-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c5f/3368799/5de376ecf27f/1755-1536-5-S1-S11-4.jpg

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本文引用的文献

1
Molecular classification and clonal differentiation of hepatocellular carcinoma: the step forward for patient selection for liver transplantation.肝细胞癌的分子分类和克隆分化:为肝移植患者选择迈出的一步。
Expert Rev Gastroenterol Hepatol. 2011 Aug;5(4):539-52. doi: 10.1586/egh.11.48.
2
Transcriptome at the time of hepatitis C virus recurrence may predict the severity of fibrosis progression after liver transplantation.肝移植后丙型肝炎病毒复发时的转录组可能预测纤维化进展的严重程度。
Liver Transpl. 2011 Jul;17(7):824-35. doi: 10.1002/lt.22309.
3
Molecular pathways differentiate hepatitis C virus (HCV) recurrence from acute cellular rejection in HCV liver recipients.
分子通路可区分 HCV 肝移植受者中 HCV 复发与急性细胞排斥反应。
Mol Med. 2011;17(7-8):824-33. doi: 10.2119/molmed.2011.00072. Epub 2011 Apr 20.
4
Fibrosis progression and the pros and cons of antiviral therapy for hepatitis C virus recurrence after liver transplantation: a review.肝移植后丙型肝炎病毒复发的纤维化进展及抗病毒治疗的利弊:综述
Transplant Proc. 2010 Jul-Aug;42(6):2223-5. doi: 10.1016/j.transproceed.2010.05.035.
5
Hepatitis C virus recurrence after liver transplantation: biomarkers of disease and fibrosis progression.丙型肝炎病毒肝移植后复发:疾病和纤维化进展的生物标志物。
Expert Rev Gastroenterol Hepatol. 2010 Aug;4(4):445-58. doi: 10.1586/egh.10.39.
6
ELISA-based detection of C4d after liver transplantation--a helpful tool for differential diagnosis between acute rejection and HCV-recurrence?基于酶联免疫吸附测定法检测肝移植后的C4d——急性排斥反应与丙型肝炎病毒复发鉴别诊断的有用工具?
Transpl Immunol. 2010 Aug;23(4):156-60. doi: 10.1016/j.trim.2010.06.002. Epub 2010 Jun 14.
7
Model for End Stage Liver Disease and hepatocellular carcinoma: a moving target.终末期肝病模型和肝细胞癌:一个移动的目标。
Transplant Rev (Orlando). 2010 Jan;24(1):11-7. doi: 10.1016/j.trre.2009.10.002.
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Prospective validation of a noninvasive index for predicting liver fibrosis in hepatitis C virus-infected liver transplant recipients.前瞻性验证一种非侵入性指数,用于预测丙型肝炎病毒感染肝移植受者的肝纤维化。
Liver Transpl. 2009 Dec;15(12):1798-807. doi: 10.1002/lt.21919.
9
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Liver Transpl. 2009 Dec;15(12):1738-49. doi: 10.1002/lt.21883.
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Expert Rev Gastroenterol Hepatol. 2009 Dec;3(6):631-47. doi: 10.1586/egh.09.58.