End-points for drug treatment in NASH

被引:11
作者
Adams, Leon A. [1 ,2 ]
机构
[1] Univ Western Australia, QEII Med Ctr, Sch Med, M503, Perth, WA 6009, Australia
[2] Sir Charles Gairdner Hosp, Dept Hepatol, Perth, WA, Australia
关键词
Non-alcoholic fatty liver disease; Clinical trials; Cirrhosis; Histology; Non-invasive fibrosis models; MRI; NONALCOHOLIC FATTY LIVER; LONG-TERM; FOLLOW-UP; NATURAL-HISTORY; STEATOHEPATITIS; FIBROSIS; ASSOCIATION; DISEASE; BIOMARKER; CIRRHOSIS;
D O I
10.1007/s12072-019-09935-6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Non-alcoholic steatohepatitis (NASH) is an increasingly common cause of cirrhosis, hepatocellular carcinoma, and liver-related death (LRD). Consequently, there is a critical need for effective drug therapy that improves clinically relevant end-points. Hepatic steatosis assessed by magnetic resonance imaging-proton density fat fraction is increasingly used in the early phase trials examining drugs with anti-steatotic effects. However, the prognostic significance of a reduction in steatosis is unknown, and thus, phase 3 trials require a histological end-point of NASH resolution without fibrosis progression. Nonetheless, it is not clear whether this end-point which requires a liver biopsy reflects a better prognosis. Thus, conditional drug approval currently requires long-term follow-up to demonstrate reduction in harder' end-points of cirrhosis, liver transplantation, and LRD. Currently, there is an essential need to develop accurate non-invasive markers that are dynamic to drug-induced changes in underlying disease severity and prognosis to utilize as surrogate end-points for clinical trials in NASH. [GRAPHICS] .
引用
收藏
页码:253 / 258
页数:6
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