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

性别和激素对丙型肝炎移植后肝纤维化的影响

• 批准号: 8436175
• 负责人: Kimberly Autumn Forde
• 金额: $ 18.21万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436175
• 关键词: Acute; Allografting; Body mass index; Cessation of life; Chronic Hepatitis C; Cirrhosis; Clinical; Confounding Factors (Epidemiology); Data; Environmental Risk Factor; Epidemiologic Studies; Estradiol; Estrogens; Europe; Evaluation; Female; Fibrosis; Gender; Genetic; Gonadal Steroid Hormones; Graft Survival; Hepatic; Hepatitis C; Hepatitis C virus; Hormonal; Human; Infection; Inflammatory; Iron; Liver Fibrosis; Liver diseases; Menopausal Status; Menopause; Modeling; Morbidity - disease rate; Outcome; Ovariectomy; Oxidative Stress; Patients; Postmenopause; Process; Production; Recording of previous events; Recurrence; Regulation; Risk Factors; Secondary to; Staging; Stratification; Testing; Transplantation; Viral; Woman; animal data; anti-hepatitis C; chronic liver disease; cytokine; design; graft failure; liver biopsy; liver transplantation; men; mortality; protective effect; response; sex

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.

描述（由申请人提供）：丙型肝炎病毒（HCV）感染是美国肝移植的主要适应症。 不幸的是，同种异体移植物的再次感染是普遍存在的。 虽然HCV复发的病程各不相同，但肝纤维化的速度却加快。 由于肝纤维化发生的速度很快，HCV 复发是肝移植后发病和死亡的主要原因。 最近的数据表明，丙型肝炎患者肝移植后的结果存在性别差异。 重要的是，女性现在被认为是同种异体移植物和患者生存率低下的新的重要风险因素。 这种差异背后的机制尚不清楚。 然而，有动物数据支持雌激素对肝纤维化过程的保护作用。 这些数据还表明，雌激素消耗状态，例如绝经期或卵巢切除术所见的雌激素消耗状态，可能会加剧肝纤维化。该提案将广泛研究性别和激素对 HCV 肝移植后肝纤维化的影响。 具体目的是确定慢性 HCV 感染肝移植后女性肝纤维化发生率是否比男性更快，确定按受者分层后临床因素是否与肝纤维化进展相关，并确定雌二醇消耗状态是否是 HCV 移植女性肝纤维化加速进展的危险因素。 使用混合效应模型，将分析上述暴露在 METAVIR 阶段的肝纤维化进展率。 调整后的混合效应模型将用于控制重要的混杂变量。