Investigation of the role of the Renin-Angiotensin System in hepatic fibrosis.

肝纤维化是慢性肝损伤的常见反应，在此期间，正常的肝脏结构被疤痕组织扭曲。肝纤维化可导致肝硬化，肝衰竭和肝细胞癌患者可能需要肝移植。慢性肝损伤可能由多种原因引起，包括酒精、持续病毒感染和代谢紊乱。导致肝脏纤维化的机制与导致其他器官如肾脏和心脏纤维化的机制相似。在这些器官中，肾素-血管紧张素系统已被证明有助于纤维化的进展。该系统尚未在肝纤维化中进行研究。我们最近在慢性丙型肝炎（HCV）患者中发现，那些基因上易产生较高水平血管紧张素的患者有更多的肝纤维化。本应用程序将研究肾素-血管紧张素系统在肝纤维化中的作用，以及使用现有药物抑制该系统是否可以降低肝纤维化的进展速度。慢性丙型肝炎病毒感染导致的肝功能衰竭目前是澳大利亚肝移植的主要指征。对于那些对抗病毒治疗没有反应的患者，目前还没有批准的治疗方案来延缓或逆转纤维化的进展。根据目前已知的HCV患者数量，估计到2020年，仅在昆士兰州，每年就有超过2000名HCV患者需要肝移植。目前可供捐献的肝脏数量每年允许大约50例移植。因此，迫切需要能够延缓或逆转肝纤维化进展的治疗方法。这项研究的成功结论将提供一种临床上有用的治疗策略，可以延缓肝纤维化的进展，从而防止许多患者需要肝移植。

Hepatic fibrosis is a common response to chronic liver injury, during which the normal liver architecture is distorted by scar tissue. Hepatic fibrosis can lead to cirrhosis and liver transplantation may be required for patients with liver failure and hepatocellular carcinoma. The chronic liver injury may result from a number of causes including alcohol, persistent viral infections and metabolic disorders. The mechanisms causing fibrosis in liver are similar to those causing fibrosis in other organs such as kidney and heart. In those organs, the renin-angiotensin system has been shown to contribute to the progression of fibrosis. This system has not been investigated in hepatic fibrosis. We have recently shown in patients with chronic hepatitis C (HCV), that those patients who are genetically pre-disposed to produce higher levels of angiotensin have more liver fibrosis. This application will investigate the role of the renin-angiotensin system in hepatic fibrosis and whether using currently available drugs to inhibit this system can decrease the rate of progression of fibrosis in liver. Liver failure due to chronic HCV infection is currently the leading indication for liver transplantation in Australia. For those patients who fail to respond to anti-viral therapy, there are currently no approved therapeutic options designed to delay or reverse the progression of fibrosis. Based on current known numbers of HCV patients it has been estimated that by the year 2020, over 2000 HCV patients will require a liver transplant each year in Queensland alone. Currently the number of donor livers available allows about 50 transplants per year. Thus there is a desperate need for therapeutic treatments that will delay or reverse the progression of hepatic fibrosis. A successful conclusion to this study will provide a clinically useful treatment strategy that can delay the progression of hepatic fibrosis and thus prevent the need for liver transplantation in many patients.