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.
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.
|Kushner, Tatyana; Shaw, Pamela A; Kalra, Ankush et al. (2018) Incidence, determinants and outcomes of pregnancy-associated hepatitis B flares: A regional hospital-based cohort study. Liver Int 38:813-820|
|Forde, Kimberly A; Bhattacharya, Debika (2017) Treatment of Hepatitis C Virus (HCV) Genotype 1 Disease. Curr Treat Options Infect Dis 9:262-276|
|Cohen, Jordana B; Eddinger, Kevin C; Locke, Jayme E et al. (2017) Survival Benefit of Transplantation with a Deceased Diabetic Donor Kidney Compared with Remaining on the Waitlist. Clin J Am Soc Nephrol 12:974-982|
|Forde, Kimberly A (2017) Ethnic Disparities in Chronic Hepatitis B Infection: African Americans and Hispanic Americans. Curr Hepatol Rep 16:105-112|
|Carr, Rotonya M; Patel, Arpan; Bownik, Hillary et al. (2017) Intestinal Inflammation Does Not Predict Nonalcoholic Fatty Liver Disease Severity in Inflammatory Bowel Disease Patients. Dig Dis Sci 62:1354-1361|
|Cohen, Jordana B; Eddinger, Kevin C; Shelton, Brittany et al. (2017) Effect of kidney donor hepatitis C virus serostatus on renal transplant recipient and allograft outcomes. Clin Kidney J 10:564-572|
|Cohen, Jordana B; Eddinger, Kevin C; Forde, Kimberly A et al. (2017) Belatacept Compared With Tacrolimus for Kidney Transplantation: A Propensity Score Matched Cohort Study. Transplantation 101:2582-2589|
|Sawinski, D; Kaur, N; Ajeti, A et al. (2016) Successful Treatment of Hepatitis C in Renal Transplant Recipients With Direct-Acting Antiviral Agents. Am J Transplant 16:1588-95|
|Small, Aaron J; Sutherland, Scott E; Hightower, Jessica S et al. (2015) Comparative risk of recurrence of dysplasia and carcinoma after endoluminal eradication therapy of high-grade dysplasia versus intramucosal carcinoma in Barrett's esophagus. Gastrointest Endosc 81:1158-66.e1-4|
|Niu, Bolin; Forde, Kimberly A; Goldberg, David S (2015) Coding algorithms for identifying patients with cirrhosis and hepatitis B or C virus using administrative data. Pharmacoepidemiol Drug Saf 24:107-11|
Showing the most recent 10 out of 15 publications