Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Organogenesis. 2021 Oct 2;17(3-4):126-135. doi: 10.1080/15476278.2021.1994273.
The prevalence of end-stage liver disease (ESLD) in the US is increasing at an alarming rate. It can be caused by several factors; however, one of the most common routes begins with nonalcoholic fatty liver disease (NAFLD). ESLD is diagnosed by the presence of irreversible damage to the liver. Currently, the only definitive treatment for ESLD is orthotopic liver transplantation (OLT). Nevertheless, OLT is limited due to a shortage of donor livers. Several promising alternative treatment options are under investigation. Researchers have focused on the effect of liver-enriched transcription factors (LETFs) on disease progression. Specifically, hepatocyte nuclear factor 4-alpha (HNF4α) has been reported to reset the liver transcription network and possibly play a role in the regression of fibrosis and cirrhosis. In this review, we describe the function of HNF4α, along with its regulation at various levels. In addition, we summarize the role of HNF4α in ESLD and its potential as a therapeutic target in the treatment of ESLD.
美国终末期肝病（ESLD）的患病率正以惊人的速度增长。它可能由多种因素引起；然而，最常见的途径之一始于非酒精性脂肪性肝病（NAFLD）。ESLD 通过对肝脏的不可逆转损伤来诊断。目前，ESLD 的唯一确定性治疗方法是原位肝移植（OLT）。然而，由于供体肝脏短缺，OLT 受到限制。一些有前途的替代治疗方案正在研究中。研究人员关注富含肝的转录因子（LETFs）对疾病进展的影响。具体来说，已经有报道称肝细胞核因子 4-α（HNF4α）重置了肝脏转录网络，并可能在纤维化和肝硬化的消退中发挥作用。在这篇综述中，我们描述了 HNF4α 的功能及其在各个水平的调节。此外，我们总结了 HNF4α 在 ESLD 中的作用及其作为 ESLD 治疗中治疗靶点的潜力。
