Gehrau Ricardo, Mas Valeria, Archer Kellie, Maluf Daniel
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.
Fibrogenesis Tissue Repair. 2012 Jun 6;5(Suppl 1):S11. doi: 10.1186/1755-1536-5-S1-S11. eCollection 2012.
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.
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。