Sex hormones and HCV-related liver disease progression

2000至2014年间，超过26万名获得退伍军人管理局医疗保健服务的男性退伍军人的实验室得到确认 丙型肝炎病毒感染的诊断。慢性丙型肝炎病毒感染(丙型肝炎病毒+)是导致肝脏疾病的主要原因 疾病进展为肝硬变、肝移植和肝癌。丙型肝炎病毒阳性的男性肝脏发病率要高得多。 疾病进展程度高于丙型肝炎病毒阳性女性。造成这种差异的一个因素可能是巨大的性别- 确定睾丸激素等循环性激素水平的生物学差异。然而，这个角色 这些主要性激素的正常变异在丙型肝炎病毒阳性人群中肝病进展的风险中起作用 同性别的人还不得而知。显著改变性别的药物的长期效果 激素水平，如睾酮治疗对丙型肝炎病毒阳性男性疾病进展风险的影响也是未知的。 我们之前招募了1072名患有慢性丙型肝炎病毒感染的男性退伍军人作为常规护理的基线队列 在单一退伍军人事务部。所有人都完成了终生风险因素调查，并采集了血液样本以获取DNA和 储存用于经批准的未来研究中的生物标记物测试。我们建议测量发行量 使用1072名队列储存的血液样本计算基线时的主要性激素水平 丙型肝炎病毒阳性男性退伍军人。我们还将进行DNA测试，以评估几个相关基因的特定变异 性激素功能。我们将前瞻性地跟踪所有肝病进展的队列成员 使用电子病历审查、退伍军人数据库搜索和专家医生确定的结果 共识审查。我们将检验性激素基线水平之间的关系 考虑性激素基因变异对肝病进展风险的影响 在我们基线的1-9年后的丙型肝炎+男性队列中，有肝硬变和肝癌。 我们建议测量改变雄激素水平的常用处方药的使用情况。 267,000名实验室确诊为丙型肝炎的男性患者中的性激素，如睾丸素 2000年至2014年在退伍军人管理局工作。我们将在以下地址提取关于每个人的大量信息 基线以说明他们接受这些药物的可能性并计算用药倾向 得分。我们将在评估该协会时考虑到这些倾向得分 使用这些激素调节药物与丙型肝炎病毒相关肝病风险之间的关系 从1-18年后的进展。 除了发现丙型肝炎病毒相关肝病进展的新的潜在治疗靶点外，这 就更好的风险分层标准而言，这项研究对临床实践具有迅速而重要的潜在影响 并帮助他们优先考虑尽早获得昂贵的抗丙型肝炎病毒新药，并可能改变做法 为感染丙型肝炎病毒的老年男性开出改变性激素的药物。

Over 260,000 male veterans accessing VA healthcare between 2000 and 2014 had a laboratory confirmed diagnosis of hepatitis C virus (HCV) infection. Chronic HCV infection (HCV+) is the leading cause of liver disease progression to cirrhosis, liver transplant and liver cancer. HCV+ males have much higher rates of liver disease progression than HCV+ females. One factor that may contribute to this difference is large and gender- defining biological differences in the levels of circulating sex hormones like testosterone. However, the role normal variability in these major sex hormones plays in risk of liver disease progression among HCV+ individuals of the same gender is not known. The long-term effects of medications that substantially alter sex hormone levels like testosterone therapy on risk of disease progression in HCV+ males are also unknown. We previously recruited baseline cohort of 1072 male veterans with chronic HCV infection seen for routine care at single VA. All completed a lifetime risk factor survey and had a blood sample taken to obtain DNA and to store for biomarker testing in approved future research studies. We propose to measure circulating levels of major sex hormones at baseline using stored blood samples for this cohort of 1,072 HCV+ male veterans. We will also perform DNA tests to assess specific variations in several genes related to sex hormone function. We will prospectively follow all cohort members for liver disease progression with outcomes determined using electronic medical record review and VA database searches and expert physician consensus review. We will examine the association between baseline levels of sex hormones after accounting for sex hormone gene variants on risk of liver disease progression including to cirrhosis and liver cancer in our baseline HCV+ male cohort from 1-9 years later. We propose to measure use of commonly prescribed medications that alter levels of androgen sex hormones like testosterone in the >267,000 males with laboratory confirmed HCV and seen at the VA between 2000 and 2014. We will extract extensive information about each individual at baseline to account for their likelihood to ever receive these medications and calculate medication propensity scores. We will account for these propensity scores in our assessment of the association between use of these hormone altering medications and risk of HCV-related liver disease progression from 1-18 years later. In addition to uncovering new potential therapeutic targets for HCV-related liver disease progression, this study has rapid and important potential impact on clinical practice in terms of better criteria to risk stratify veterans and help prioritize them for early access to costly new anti-HCV medications and may alter practice for prescribing sex hormone altering medications in aging HCV-infected males.