Modeling the Disease Burden and Cost-Effectiveness of Screening and Treatment for Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes Patients

项目概要/摘要 在美国，2型糖尿病（T2D）是由于微血管和血管病变引起的发病率和死亡率的主要原因。 大血管并发症非酒精性脂肪肝（NAFLD）是另一种常见的合并症，但其 T2D患者的负担研究较少。虽然NAFLD影响50 - 70%的T2D患者，但两者都没有。 没有NAFLD的筛查指南或既定治疗。除了减肥，吡格列酮-一种古老的 糖尿病药物-是美国肝病研究协会推荐的唯一药物， 在T2D患者中治疗NASH（NAFLD的更进展形式）。此外，利拉鲁肽（II期） 试验）和奥贝胆酸（3期中期数据）似乎有效改善NASH和晚期 纤维化至少有4种其他药物（总共5种）正在进行3期试验，多达50种药物正在进行中。 第二阶段试验。随着新药在不久的将来上市，医生和患者将面临困难。 权衡长期利益、风险和成本。考虑到NAFLD在患者中的广泛性， T2D，筛查以识别处于晚期肝病高风险的NASH患者，以便进行早期干预 可以帮助患者活得更长，生活质量更高。然而，由于缺乏相对有效性和成本- NAFLD筛查的有效性分析导致了相互矛盾的临床指南。选择最佳 NAFLD的治疗和筛查策略是复杂的，可以通过使用基于计算机的 模型不幸的是，现有的糖尿病模型不包括NAFLD，并且NAFLD模型不考虑 糖尿病及其并发症。本研究的目的是建立一个NAFLD的计算机模拟模型 评估其负担，并评估NASH的治疗和筛查选择。具体目标是：1） 开发和验证NAFLD自然史的微观模拟模型，包括NASH; 2）估计 并预测到2030年T2D患者中NAFLD相关肝脏并发症的负担; 3）评估 2型糖尿病患者NASH治疗的成本效益;以及4）评价 在T2D患者中筛查NASH。这项建议建立在我们跨学科团队的强大 建立决策模型以辅助临床决策和研究流行病学的基础 糖尿病和NAFLD。我们的模型将提供一个更好的理解一个普遍的，重要的，但 未被充分认识的糖尿病并发症，使用创新方法进行糖尿病和肝脏疾病建模。 这项研究也为将来评估新的治疗方案和筛查奠定了基础 T2D和NAFLD患者的治疗模式，这将促进这两种疾病的预防和治疗 每年都有数百万的病人。

Project Summary/Abstract In the US, type 2 diabetes (T2D) is a major cause of morbidity and mortality due to microvascular and macrovascular complications. Nonalcoholic fatty liver disease (NAFLD) is another common co-morbidity but its burden in patients with T2D is poorly studied. Although NAFLD affects 50-70% of T2D patients, there is neither a screening guideline nor established treatment for NAFLD. Besides weight loss, pioglitazone – an old diabetes drug – is the only drug recommended by the American Association for the Study of Liver Diseases for treating NASH, the more progressive form of NAFLD, in patients with T2D. In addition, liraglutide (in phase 2 trials) and obeticholic acid (with phase 3 interim data) appear effective for improving NASH and advanced fibrosis. At least 4 other drugs (making a total of 5) are undergoing phase 3 trials and up to 50 drugs are in phase 2 trials. As new drugs become available in the near future, physicians and patients will face difficult tradeoffs among long-term benefits, risks, and costs. Given the widespread nature of NAFLD in patients with T2D, screening to identify those with NASH, who are at high-risk of advance liver disease, for early intervention may help patients live longer with a better quality life. Yet, the lack of comparative effectiveness and cost- effectiveness analyses of screening for NAFLD has resulted in conflicting clinical guidelines. Choosing the best treatment and screening strategy for NAFLD is complicated and can be aided by the use of computer-based models. Unfortunately, existing diabetes models do not include NAFLD, and NAFLD models do not account for diabetes and its complications. The objective of this study is to develop a computer simulation model of NAFLD in T2D to estimate its burden, and evaluate treatment and screening options for NASH. Specific aims are: 1) Develop and validate a microsimulation model of the natural history of NAFLD, including NASH; 2) Estimate and project the burden of NAFLD-associated liver complications in patients with T2D until 2030; 3) Assess the cost-effectiveness of treatments for NASH in patients with T2D; and 4) Evaluate the cost-effectiveness of screening for NASH in patients with T2D. This proposal builds upon our inter-disciplinary team’s strong foundation of constructing decision models to assist clinical decision making and studying the epidemiology of diabetes and NAFLD. Our model will provide a better understanding of a prevalent, important, yet underappreciated diabetes complication, using an innovative approach to diabetes and liver disease modeling. The study also establishes the groundwork for future evaluation of new treatment regimens and screening modalities for patients with T2D and NAFLD, which will advance the prevention and treatment of both diseases for millions of patients each year.