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

WELL 研究（肝脏健康健康教育研究）：减少有遗传倾向的成年人的肝病

• 批准号: 10112901
• 负责人: Laura Saslow
• 金额: $ 11.7万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112901
• 关键词: Adherence; Adult; Behavioral; Body Weight; Body Weight decreased; Body mass index; Carbohydrates; Cirrhosis; Clinical; Clinical Trials; Data; Deposition; Diet; Disease; Disease Outcome; Dropout; Education; Evidence based intervention; Fatty Liver; Fatty acid glycerol esters; Feedback; Fibrosis; Formulation; Future; Genetic; Genetic Predisposition to Disease; Genomics; Genotype; Glucose; Goals; Grant; Guidelines; Health; Hepatitis C; Hypertension; Individual; Inflammation; Insulin Resistance; Intervention; Interview; Life Style; Lipids; Liver; Liver Fibrosis; Liver diseases; Magnetic Resonance Imaging; Medical Care Costs; Methods; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Insulin-Dependent Diabetes Mellitus; Participant; Patients; Pharmaceutical Preparations; Pilot Projects; Polycystic Ovary Syndrome; Population; Prediabetes syndrome; Prevalence; Primary carcinoma of the liver cells; Protons; Randomized Controlled Trials; Research; Research Project Grants; Research Support; Resources; Risk; Risk Factors; STEM research; Serum; Structure; Testing; Time; Weight; acceptability and feasibility; arm; base; density; dietary; dietary adherence; high risk; improved; insulin sensitivity; intrahepatic; liver transplantation; modifiable risk; mortality; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; personalized medicine; preference; programs; satisfaction; treatment strategy

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.

摘要