Departments of Surgery and Biomedical Sciences, Marshall University Joan C. Edwards School of Medicine, Huntington, WV 25755, USA.
Int J Mol Sci. 2020 Jul 3;21(13):4737. doi: 10.3390/ijms21134737.
Hepatic fibrosis has been associated with a series of pathophysiological processes causing excessive accumulation of extracellular matrix proteins. Several cellular processes and molecular mechanisms have been implicated in the diseased liver that augments fibrogenesis, fibrogenic cytokines and associated liver complications. Liver biopsy remains an essential diagnostic tool for histological evaluation of hepatic fibrosis to establish a prognosis. In addition to being invasive, this methodology presents with several limitations including poor cost-effectiveness, prolonged hospitalizations, and risks of peritoneal bleeding, while the clinical use of this method does not reveal underlying pathogenic mechanisms. Several alternate noninvasive diagnostic strategies have been developed, to determine the extent of hepatic fibrosis, including the use of direct and indirect biomarkers. Immediate diagnosis of hepatic fibrosis by noninvasive means would be more palatable than a biopsy and could assist clinicians in taking early interventions timely, avoiding fatal complications, and improving prognosis. Therefore, we sought to review some common biomarkers of liver fibrosis along with some emerging candidates, including the oxidative stress-mediated biomarkers, epigenetic and genetic markers, exosomes, and miRNAs that needs further evaluation and would have better sensitivity and specificity. We also aim to elucidate the potential role of cardiotonic steroids (CTS) and evaluate the pro-inflammatory and profibrotic effects of CTS in exacerbating hepatic fibrosis. By understanding the underlying pathogenic processes, the efficacy of these biomarkers could allow for early diagnosis and treatment of hepatic fibrosis in chronic liver diseases, once validated.
肝纤维化与一系列导致细胞外基质蛋白过度积累的病理生理过程有关。几种细胞过程和分子机制已被牵涉到肝脏疾病中，这些机制会加剧纤维化、成纤维细胞因子和相关的肝脏并发症。肝活检仍然是评估肝纤维化组织学以确定预后的重要诊断工具。除了具有侵袭性外，这种方法还存在一些局限性，包括成本效益差、住院时间延长和腹膜出血的风险，而该方法的临床应用并不能揭示潜在的发病机制。已经开发了几种替代的非侵入性诊断策略，以确定肝纤维化的程度，包括使用直接和间接生物标志物。通过非侵入性手段立即诊断肝纤维化将比活检更能被接受，并且可以帮助临床医生及时进行早期干预，避免致命并发症，并改善预后。因此，我们试图回顾一些常见的肝纤维化生物标志物以及一些新兴的候选标志物，包括氧化应激介导的生物标志物、表观遗传和遗传标志物、外泌体和 miRNA，这些标志物需要进一步评估，并且具有更好的敏感性和特异性。我们还旨在阐明强心甾类（CTS）的潜在作用，并评估 CTS 对炎症和纤维化的促发作用，以加重肝纤维化。通过了解这些潜在的发病机制，这些生物标志物的疗效可以允许在慢性肝病中进行肝纤维化的早期诊断和治疗，一旦得到验证。
