Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop.
Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop.
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DOI：
10.1002/hep.27678
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发表时间：
2015-04
期刊：
影响因子：
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通讯作者：
United States Food and Drug Administration
中科院分区：
文献类型：
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作者：
Sanyal AJ;Friedman SL;McCullough AJ;Dimick-Santos L;American Association for the Study of Liver Diseases;United States Food and Drug Administration
非酒精性脂肪性肝病(NAFLD)是北美慢性肝病最常见的原因。它是需要肝移植的慢性肝病负担的越来越大的贡献者。在非酒精性脂肪性肝炎(NASH)患者中，即使在没有肝硬变的情况下，肝细胞癌的风险也可能增加。NASH是非酒精性脂肪性肝炎的组织形式，与肝脏相关的死亡率增加有关。NASH的诊断目前需要肝脏活检。目前也没有FDA批准的治疗NASH的方法。因此，有必要为NASH患者制定更好的诊断和治疗策略，既针对早期疾病，也针对晚期肝纤维化患者。在为这些目标人群设计研究方面存在着独特的挑战。NAFLD和NASH进展到肝硬变和最终肝功能衰竭的相对无症状的较长时间间隔，以及关于疾病修饰物的知识差距，共同构成了试验设计中的重大挑战。因此，迫切需要制定方法，以确定疾病进展的特殊风险人群，并确认反映这一人群健康状况有意义变化的终点。这篇手稿总结了2013年9月5日和6日在马里兰州银泉举行的联合研讨会上的讨论，该研讨会由FDA和AASLD赞助，旨在制定NASH诊断和治疗方法的指南。
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in North America. It is a growing contributor to the burden of chronic liver disease requiring liver transplantation. Cirrhosis is also associated with an increased risk of hepatocellular cancer which may occur even in the absence of cirrhosis in subjects with nonalcoholic steatohepatitis (NASH) the histological form of NAFLD associated with increased liver-related mortality. The diagnosis of NASH currently requires a liver biopsy. There are also no FDA-approved therapies for NASH. There is therefore a need to develop better diagnostic and therapeutic strategies for patients with NASH targeting both those with early stage disease as well as those with advanced liver fibrosis. There are unique challenges in the design of studies for these target populations. The long relatively asymptomatic time interval in the progression of NAFLD and NASH to cirrhosis and ultimately liver failure, along with gaps in knowledge regarding disease modifiers combine to present significant challenges in trial design. There is therefore an urgent need to develop methods to identify the populations at particular risk of disease progression and to validate endpoints that reflect meaningful changes in health status in this population. This manuscript summarizes the discussion at a joint workshop held September 5th and 6th, 2013, in Silver Spring, Maryland, sponsored by the FDA and the AASLD to develop guidance on diagnostic and therapeutic modalities for NASH.