Caillot Frédérique, Hiron Martine, Goria Odile, Gueudin Marie, Francois Arnaud, Scotte Michel, Daveau Maryvonne, Salier Jean-Philippe
Inserm Unité 905, Faculté de Médecine-Pharmacie, Rouen cedex, France.
Am J Pathol. 2009 Jul;175(1):46-53. doi: 10.2353/ajpath.2009.080850. Epub 2009 May 28.
Liver biopsy is considered the gold-standard method for the assessment of liver fibrosis during follow-up of hepatitis C virus-infected patients, but this invasive procedure is not devoid of complications. The aim of the present study was to identify novel non-invasive markers of fibrosis progression. By microarray analysis, we compared transcript levels in two extreme stages of fibrosis from 16 patients. Informative transcripts were validated by real-time PCR and used for the assessment of fibrosis in 23 additional patients. Sixteen transcripts were found to be dysregulated during the fibrogenesis process. Among them, some were of great interest because their corresponding proteins could be serologically measured. Thus, the protein levels of inter-alpha inhibitor H1, serpin peptidase inhibitor clade F member 2, and transthyretin were all significantly different according to the four Metavir stages of fibrosis. In conclusion, we report here that dysregulation, at both the transcriptional and protein levels, exists during the fibrogenesis process. Our description of three novel serum markers and their potential use as serological tests for the non-invasive diagnosis of liver fibrosis open new opportunities for better follow-up of hepatitis C virus-infected patients.
肝活检被认为是丙型肝炎病毒感染患者随访期间评估肝纤维化的金标准方法，但这种侵入性操作并非没有并发症。本研究的目的是确定纤维化进展的新型非侵入性标志物。通过微阵列分析，我们比较了16例患者两个极端纤维化阶段的转录水平。通过实时PCR验证了有信息价值的转录本，并将其用于另外23例患者的纤维化评估。发现16个转录本在纤维化过程中表达失调。其中一些非常有趣，因为它们相应的蛋白质可以通过血清学方法检测。因此，根据纤维化的四个梅塔维（Metavir）阶段，α-间抑制剂H1、丝氨酸蛋白酶抑制剂F家族成员2和转甲状腺素蛋白的蛋白质水平均有显著差异。总之，我们在此报告，在纤维化过程中存在转录和蛋白质水平的失调。我们对三种新型血清标志物的描述及其作为肝纤维化非侵入性诊断血清学检测的潜在用途，为更好地随访丙型肝炎病毒感染患者开辟了新的机会。
