HIV and hepatic inflammation and fibrosis

 描述（由申请人提供）：由于HIV的稳定发病率（2006年估计为53，600/例/年）和有效抗逆转录病毒治疗导致的预期寿命延长，美国的HIV流行率正在增加（7）。由于HIV患者在有效的ART环境中继续活得更长，肝病已成为非艾滋病相关死亡的主要原因（1）。由于共同的传播途径，HCV和HBV在HIV感染者中很常见，尽管其他慢性肝病如酒精和脂肪肝也在出现。流行病学数据表明，HIV加速了各种肝脏疾病引起的肝纤维化。HIV/HCV合并感染患者至肝硬化的中位时间比HCV单一感染患者早约12年（11，12）。在HIV/HBV合并感染的情况下，HIV/HBV合并感染的患者死于肝病的可能性比仅感染HIV的患者高8倍，死于肝病的可能性比HBV单感染者高19倍（14）。在HIV单一感染的患者中，NASH正在成为肝脏疾病的一个原因。鉴于供体器官的短缺，移植的经济负担（15），以及患有基础肝病的HIV +患者的老龄化队列，迫切需要为这一人群开发抗纤维化治疗。该应用程序的重点是了解HIV如何与肝脏中的2个关键细胞相互作用，这些细胞在肝脏炎症和纤维化中发挥重要作用：1）激活肝星状细胞和2）肝脏巨噬细胞（枯否细胞）。我们还将研究是否库普弗细胞是一个水库艾滋病毒的患者谁是抗逆转录病毒治疗。时发现的问题 应用将为HIV +患者带来创新的抗纤维化方法， 移植的需要，并将促进我们对艾滋病毒水库的理解，这对找到治愈艾滋病毒至关重要。

 DESCRIPTION (provided by applicant): HIV prevalence in the US is increasing due to a combination of the stable incidence of HIV (estimate at 53,600/cases year in 2006) and the longer life expectancy due to effective antiretroiral therapies (7). As HIV patients continue to live longer in the setting of effective ART, live disease has become the leading cause of non­AIDS related mortality (1). Because of shared routes of transmission, HCV and HBV are common in HIV­infected patients though other chronic liver diseases such as alcohol and fatty liver disease are also emerging.Epidemiologic data suggests that HIV accelerates liver fibrosis from a variety of liver diseases. Median time to cirrhosis in HIV/HCV coinfected patients is approximately 12 years sooner than HCV monoinfected patients(11,12). In the case of HIV/HBV coinfection, HIV/HBV coinfected patients are more than 8X likely to die from liver disease than those infected with HIV alone and 19X more likely to die from liver disease than HBV monoinfected individuals (14). In HIV monoinfected \ patients, NASH is emerging as a cause of liver disease. Given the shortage of donor organ, the economic burden of transplant (15), and the aging cohort of HIV + patients with underlying liver disease, there is an urgent need for the development of anti­fibotic treatments for this population. This application focuses on understanding how HIV interacts with 2 key cells in the liver which play an important in liver inflammation and fibrosis: 1) the activate hepatic stellate cell and 2) the liver macrophages (Kupffer cells). We will also examine if Kupffer cells are a reservoir for HIV in patients who are on anti­retroviral therapies. Findings from this application will lead to innovative antifibrotic approaches for HIV + patients that may prevent the need for transplant and will advance our understanding of HIV reservoirs which is critical to finding a cure for HIV.