The WELL Study (Wellness Education for Liver Health Study): Reducing liver disease in genetically predisposed adults

摘要 目前没有药物可用于治疗非酒精性脂肪肝（NAFLD）， 越来越普遍的疾病折磨着大约25%的美国成年人。NAFLD是由脂肪沉积过多引起的 肝脏（脂肪变性）;可进展为非酒精性脂肪性肝炎（NASH）、纤维化、肝硬化、肝细胞性 癌症、肝移植和增加的肝脏相关和全因死亡率。我们有初步数据 （1）胰岛素抵抗是发展NAFLD的最强可改变的风险因素，以及（2）个体 通过携带PNPLA 3 rs738409-GG而遗传上易患NAFLD的人显示出约两倍的风险增加， 与胰岛素联合使用时，发生NAFLD和非酒精性脂肪性肝炎（NASH）的风险增加6倍 阻力尽管rs738409-GG具有胰岛素抵抗的个体处于肝病的高风险中， 特别针对性地帮助他们提高胰岛素敏感性，从而可能改善他们的NAFLD 结果。PI和其他人已经表明，非常低碳水化合物的饮食（VLCD）更有效， 比许多其他类型的饮食减少胰岛素抵抗，除了对减肥有效， 降低总体炎症和降低肝内脂质含量。我们假设一个很低的- 碳水化合物饮食和行为支持计划可能能够在患有NAFLD的成年人中实现NAFLD逆转。 脂肪变性和/或轻度纤维化，特别是在高危亚群rs738409-GG个体中。以准备 测试这一点，我们将进行初步探索的需求和偏好的个人与NAFLD的， VLCD程序。然后，我们将根据这些反馈调整我们的材料。最后，我们将进行试点 在30名患有NAFLD的PNPLA 3 rs738409 GG成人中进行4个月VLCD计划的可行性和可接受性试验。 该R 03是在PI当前的K 01和NIDDK的基础上构建的，该K 01正在优化一个为期12个月的VLCD计划， 2型糖尿病患者的饮食我们预计，这项研究将导致未来的R级 国家糖尿病、消化和肾脏疾病研究所的赠款，因为它将为一个 多中心随机对照试验。

ABSTRACT No medications are currently available for treatment of nonalcoholic fatty liver disease (NAFLD), an increasingly prevalent disease afflicting about 25% of US adults. NAFLD is caused by excessive fat deposition in the liver (steatosis); can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, hepatocellular carcinoma, liver transplantation, and increased liver-related and all-cause mortality. We have preliminary data that (1) insulin resistance is the strongest modifiable risk factor for developing NAFLD, and (2) individuals genetically predisposed to NAFLD by carrying PNPLA3 rs738409-GG show about a two-fold increased risk of developing NAFLD and a six-fold risk of nonalcoholic steatohepatitis (NASH) when combined with insulin resistance. Despite being at high risk of liver disease, rs738409-GG individuals with insulin resistance are not being especially targeted to help them improve their insulin sensitivity and thus likely improve their NAFLD outcomes. The PI and others have shown that very low-carbohydrate diets (VLCD) are more effective at reducing insulin resistance than many other types of diets, in addition to being effective for weight loss, lowering overall inflammation, and reducing intrahepatic lipid content. We hypothesize that a very low- carbohydrate diet and behavioral support program may be able to achieve NAFLD reversal in adults with steatosis and/or mild fibrosis, especially in a high-risk subpopulation, rs738409-GG individuals. To prepare to test this we will conduct a preliminary exploration of the needs and preferences of individuals with NAFLD for a VLCD program. Then we will adapt our materials based on this feedback. Finally, we will conduct a pilot feasibility and acceptability trial of a 4-month VLCD program in 30 PNPLA3 rs738409 GG adults with NAFLD. This R03 builds off of the PI’s current K01 with NIDDK, which is optimizing a 12-month VLCD program with adults with type 2 diabetes. We anticipate that the research stemming from this grant will lead to future R-level grants at the National Institute of Diabetes and Digestive and Kidney Diseases, as it will provide support for a multicenter randomized controlled trial.