跟踪非酒精性脂肪性肝病的临床试验-病理学终点评价

蒋丽娜; 赵景民

doi:10.3969/j.issn.1001-5256.2018.12.004

跟踪非酒精性脂肪性肝病的临床试验-病理学终点评价

DOI: 10.3969/j.issn.1001-5256.2018.12.004

解放军第三〇二医院病理诊断与研究中心

基金项目:

首都卫生发展科研专项项目(首发2014-2-5032)；国家自然科学基金青年项目(81500450);国家自然科学基金面上项目(81673654)；

详细信息

中图分类号: R575
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出版历程
- 出版日期: 2018-12-20

A clinical trial on the follow-up of nonalcoholic fatty liver disease: An evaluation of pathological endpoint

Research funding:

摘要

摘要: 肝活组织检查是非酒精性脂肪性肝病（NAFLD）/非酒精性脂肪性肝炎（NASH）诊断的"金标准",尽管肝穿刺检查存在有创性、取样和评价误差等局限性,但在跟踪NAFLD/NASH临床试验研究及新药临床试验中,肝组织学评价仍是研究队列入组诊断与排除诊断、主要治疗终点评价的主要指标,不可替代。NASH进展为肝硬化通常延续10～20年,作为新药临床中的替代终点,推荐美国NASH临床研究网络评分系统（NASH-CRN）为跟踪NAFLD/NASH临床试验中的组织学评价系统。NASH的主要治疗终点通常设定为NASH逆转,且无纤维化进展,或主要治疗终点为NAS评分下降2分或以上,且至少一个以上组织学参数降低1分以上,无纤维化进展,完成全程治疗。2b期和3期临床试验的周期至少应观察12个月,如果将纤维化改善作为主要评价指标则至少需要1～2年,且需要在停药后跟踪随访6个月以上。组织学评价受多种因素影响,为保证评价质量,穿刺肝组织应大于2 cm（包含10个以上完整的汇管区）,建议进行集中切片染色,并由2名以上肝病病理专家进行单盲或双盲病理集中阅片,避免染色及阅片偏倚。
- 非酒精性脂肪性肝病 /
- 肝硬化 /
- 病理过程 /
- 活组织检查,针吸 /
- 临床试验
Abstract: Liver biopsy is the“gold standard”for the diagnosis of nonalcoholic fatty liver disease (NAFLD) /nonalcoholic steatohepatitis (NASH) . Although liver biopsy has several limitations including invasiveness and errors in sampling and evaluation, in clinical trials on NAFLD/NASH follow-up and new drugs, liver histological evaluation is still a main and irreplaceable method for inclusion/exclusion diagnosis and assessment of primary endpoints in cohorts. It often takes 10-20 years for NASH to progress to liver cirrhosis, which is a surrogate endpoint in clinical trials for new drugs, and the NASH Clinical Research Network (NASH-CRN) system is recommended as the histological evaluation system in clinical trials for tracking NAFLD/NASH. The primary endpoint for NASH treatment is usually set as the reversal of NASH without progression of fibrosis; an alternative one is a reduction in NAS score by at least 2 points and a reduction in one or more histological parameters by at least 1 point, without progression of fibrosis, during the full-course treatment. Patients in phase 2 b and 3 clinical trials should be monitored for at least 12 months, and if the improvement of fibrosis is set as the main assessment index, they should be monitored for at least 1-2 years and should be followed up for more than 6 months after drug withdrawal. Histological evaluation is affected by various factors. In order to ensure the quality of such evaluation, the length of tissue for liver biopsy should be larger than 2 cm (containing more than 10 portal areas) . Staining and section preparation should be performed at the same time, and more than two experts specializing in liver pathology should perform single-or double-blinded review of liver biopsies to avoid evaluation bias.
- non-alcoholic fatty liver disease /
- liver cirrhosis /
- pathologic processes /
- biopsy, needle /
- clinical trial

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参考文献(28)

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