HIV and hepatic inflammation and fibrosis

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

Linked publications & trials

Abstract

? 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.