Hepatocyte replicative arrest, hepatic progenitor cells and the ductular reaction in hepatic fibrogenesis

慢性肝病如丙型肝炎和肥胖相关的脂肪肝可能与瘢痕形成有关，最终导致肝硬化和肝功能衰竭。我们不确定为什么会出现这种疤痕，但随着肝炎和脂肪肝变得越来越常见，有必要了解这个过程，以便开发有效的治疗方法。这项研究着眼于一种可能的机制来解释肝脏瘢痕的发展。我们认为，肝脏的正常修复机制导致肝细胞的产生，以取代那些已经死亡，但在某些情况下，也产生小胆管，从肝细胞中排出胆汁。这些小胆管可能在刺激瘢痕形成中具有先前未被怀疑的作用。该研究将观察小胆管是否在人类的一系列肝脏疾病中产生，并将使用啮齿动物模型来寻找刺激疤痕的因素。当这个过程被更清楚地理解时，它可能会导致新的或更有效的治疗方法的开发，以减少甚至逆转肝脏瘢痕形成。

Chronic liver diseases such as hepatitis C and obesity-related fatty liver can be associated with scarring that eventually results in cirrhosis and liver failure. We are unsure why this scarring occurs, but as hepatitis and fatty liver are becoming more common it is necessary to understand this process so that effective therapies can be developed. This study looks at one possible mechanism to explain the development of liver scarring. We believe that the normal repair mechanisms of the liver lead to the production of liver cells to replace those that have died, but in some circumstances also produce small bile ducts that drain bile from the hepatocytes. These small bile ducts may have a previously unsuspected role in stimulating the scar formation. The study will see if the small bile ducts are produced in a range of liver diseases in humans, and will use rodent models to find the factors responsible for stimulating the scarring. When the process is understood more clearly, it could lead to the development of new or more effective therapies to reduce or even reverse liver scarring.