Nonalcoholic Steatohepatitis Clinical Research Network

描述(由申请人提供)： 非酒精性脂肪性肝病(NAFLD)是美国慢性肝病的常见原因。它包括脂肪肝和非酒精性脂肪性肝炎(NASH)。NASH临床研究网络(NASH CRN)成立于2002年，旨在开展与儿童和成人NAFLD的临床特征、危险因素、发病机制、自然病史和治疗相关的研究。NIDDK受到其成功的鼓舞，发布了RFA-DK-08-505，其目标是将NASH CRN再延续五年。NASH CRN在未来五年的目标是：(1)成功地完成在最初筹资期间启动的三项全网研究。这些研究包括成人和儿童NAFLD的观察性纵向研究(NAFLD数据库研究，n=1215)，在患有NASH的非糖尿病成人中进行的吡格列酮或维生素E与安慰剂(Pivens)的随机双盲对照试验(n=247)，以及二甲双胍或维生素E与安慰剂(奎宁)的随机双盲对照试验(n=173)。这些研究都被完全录取了。NAFLD数据库将被修订，以允许进一步跟踪登记的受试者，对选定的受试者进行肝脏活检，并增加仔细定义的对照以及其他患有NAFLD的受试者。这样做的基本原理是：(2)完成已经启动的许多先导性和辅助研究，(3)在成人和儿童NASH患者中进行额外的治疗试验，(3)开发和验证生物标记物，以及完成尽管使用了当前的数据库，但仍然动力不足的辅助研究。具体研究将基于NASH CRN指导委员会和NIDDK批准的个别中心提出的建议，以及(4)进行个别中心提出的新的辅助研究。该中心提出了两项研究：(A)验证NASH的代谢特征。初步研究已经确定了NASH的一个明显的脂类特征：(B)为体重指数在30-45之间的成年NASH患者进行一项随机对照试验，即进行腹腔镜可调束带胃成形术(LABG)。这项试验将检验LABG是治疗NASH安全有效的假设。总而言之，所有这些研究都与NIH针对NAFLD的肝脏行动计划直接一致。 公共卫生相关性：(由申请人提供)：非酒精性脂肪肝和非酒精性脂肪肝是重要的健康问题，其发病率预计会增加。在最初的资助期间，CRN为NAFLD和NASH领域做出了重要贡献，但仍然存在许多悬而未决的问题。在下一个资助期间，CRN将继续调查NASH和相关疾病的风险因素、临床方面、自然病史和最佳治疗方法。

DESCRIPTION (provided by applicant): Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in the United States. It encompasses both a fatty liver and nonalcoholic steatohepatitis (NASH). The NASH Clinical Research Network (NASH CRN) was established in 2002 to conduct research related to the clinical features, risk factors, pathogenesis, natural history and treatment of NAFLD in children and adults. Encouraged by its success, the NIDDK has issued RFA-DK-08-505 whose objective is to continue the NASH CRN for five more years. The objectives of the NASH CRN during the next five years are: (1) to successfully complete three network wide studies initiated during the initial funding period. These include an observational longitudinal study of NAFLD in adults and children (NAFLD database study, n=1215), a randomized double blind controlled trial of pioglitazone or vitamin E vs. placebo (PIVENS) (n=247) in nondiabetic adults with NASH, and a randomized double blind controlled trial of metformin or vitamin E vs. placebo (TONIC) (n= 173). These studies are fully enrolled. The NAFLD database will be amended to allow further follow up of enrolled subjects, perform liver biopsies on selected subjects and add carefully defined controls as well as additional subjects with NAFLD. The rationale for this is to definitively evaluate the natural history of the disease, develop and validate biomarkers and complete ancillary studies that are still underpowered despite use of the current database, (2) to complete the numerous pilot and ancillary studies that have been initiated, (3) to perform additional therapeutic trials in adults and children with NASH. The specific studies will be based on proposals received from individual centers that are approved by the NASH CRN steering committee and the NIDDK for which funding is available, and (4) to conduct new ancillary studies proposed by individual centers. Two studies are proposed by this center: (a) to validate the metabolomic signature of NASH. Preliminary studies have identified a distinct lipidomic signature of NASH, (b) to perform a randomized controlled trial of laparoscopic adjustable band gastroplasty (LABG) for adults with NASH who have a BMI between 30-45. This trial will test the hypothesis that LABG is a safe and effective treatment of NASH. Together, all of these studies are directly aligned with the NIH liver action plan for NAFLD. Public Health Relevance: (provided by the applicant): NAFLD and NASH are important health problems and their incidence is expected to increase. During the initial funding period, the CRN has made important contributions to the field of NAFLD and NASH, however there remain numerous unanswered questions. During the next funding period, the CRN will continue to investigate risk factors, clinical aspects, natural history and optimal treatment for NASH and associated conditions