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.

Public Health Relevance

Women who have had a liver transplant for hepatitis C have poorer outcomes than men who have been transplanted for the same indication. It may be that the absence of female sex hormones like estrogen, as is seen in postmenopausal women, influences the disparate outcomes. If this is found to be the case, this critical information will help to guide the testing of new therapies and alter the approach to HCV therapy in women after transplant.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Podskalny, Judith M,
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University of Pennsylvania
Internal Medicine/Medicine
Schools of Medicine
United States
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Bahirwani, Ranjeeta; Forde, Kimberly A; Mu, Yifei et al. (2014) End-stage renal disease after liver transplantation in patients with pre-transplant chronic kidney disease. Clin Transplant 28:205-10