Gender and hormonal influences on liver fibrosis after transplant for hepatitis C

University Of Pennsylvania, Philadelphia PA

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Abstract

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the US. Unfortunately, re-infection of the allograft is universal. Though the course of recurrent HCV is variable, the rate of hepatic fibrosis is accelerated. Because of the rapidity with which hepatic fibrosis occurs, recurrent HCV is a major cause of morbidity and mortality after liver transplant. Recent data suggest that a gender disparity exists in the setting of post liver transplant outcomes for HCV patients. Importantly, female sex is now appreciated as a new and significant risk factor for poor allograft and patient survival. The mechanisms underlying this disparity are not well understood. However, there are animal data that support a protective effect of estrogen on the process of hepatic fibrosis. These data also suggest that estrogen deplete states, such as that seen with menopause or oophorectomy, may enhance hepatic fibrosis. This proposal will broadly examine the effect of gender and hormonal Influences on hepatic fibrosis after liver transplantation for HCV. The specific aims are to determine whether women have more rapid rates of hepatic fibrosis than men after liver transplantation for chronic HCV infection, to determine whether clinical factors are associated with hepatic fibrosis progression after stratifying by recipient se and to determine if an estradiol-deplete state is a risk factor for accelerated fibrosis progressio in women transplanted for HCV. Using mixed effects models, hepatic fibrosis progression rates, in METAVIR stages, will be analyzed for the above exposures. Adjusted mixed effects models will be utilized to control for important confounding variables.