The introduction of combination anti-retroviral therapy (ART) resulted in dramatic reductions in AIDS-related mortality and improvements in the prognosis for HIV-infected patients. However, co-morbidities have become the most pressing issue in the management of HIV-infection. Among these, nonalcoholic fatty liver disease (NAFLD) has emerged as a frequent cause of liver disease and a new challenge in the management of HIV-infected patients. NAFLD is considered the most common chronic liver disease in the U.S., with an incidence over 25% in non HIV-infected individuals and over 35% in HIV-infected patients. The clinical presentation of NAFLD can range from the non-progressive form, characterized by simple hepatic steatosis, to the progressive forms, characterized by inflammation (i.e., non-alcoholic steatohepatitis [NASH]) and fibrosis. While the etiology of NAFLD is related to metabolic risk factors such as obesity, insulin resistance and the metabolic syndrome, there is evidence that the prevalence of NAFLD, NASH and liver fibrosis as well as the severity of liver disease in HIV-infected patients are even higher compared to the general population. However, there is limited information regarding the natural history of NAFLD progression in HIV-positive vs. negative individuals as well their potential biochemical, pathological and clinical differences. Since most of the available data of NAFLD in HIV-infected populations is disproportionately based on studies of male subjects, there is a need to study the natural history of NAFLD in women.
The goal of this pilot project is to gain an insight into the potential mechanisms whereby HIV infection influences NAFLD in women as well as to identify potential biomarkers to help identify those at risk of developing progressive liver disease among HIV-infected patients. Hypothesis: HIV infection increases the risk of NAFLD and hastens its progression through effects on: a) increased intestinal permeability leading to bacterial translocation and inflammation; b) alterations to adipose tissue function resulting in altered adipokine production; and c) an altered fibrinolytic system leading to a pro-fibrotic environment.