磁共振质子密度脂肪分数——一种具有潜力的非酒精性脂肪性肝炎临床试验替代终点

安梓铭; 冯琴

doi:10.3969/j.issn.1001-5256.2021.06.047

磁共振质子密度脂肪分数——一种具有潜力的非酒精性脂肪性肝炎临床试验替代终点

DOI: 10.3969/j.issn.1001-5256.2021.06.047

安梓铭¹,
冯琴^{1, 2, 3, 4, ,}

1.
上海中医药大学附属曙光医院肝病研究所, 上海 201203
2.
上海中医药大学肝病研究所, 上海 201203
3.
上海市中医临床重点实验室, 上海 201203
4.
肝肾疾病病证教育部重点实验室, 上海 201203

基金项目:

上海市科委科技支撑项目 (19401972100);

上海申康医院发展中心临床三年行动计划资助 (SHDC2020CR4051)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：安梓铭负责资料分析和撰写论文；冯琴负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
安梓铭(1995—)，男，主要从事中西医结合防治非酒精性脂肪性肝病的临床与基础研究

通信作者:
冯琴，fengqin1227@163.com

中图分类号: R575.5
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- 被引次数: 0
出版历程
- 收稿日期: 2020-11-02
- 录用日期: 2020-12-04
- 出版日期: 2021-06-20

Magnetic resonance imaging-proton density fat fraction: A potential surrogate endpoint for nonalcoholic steatohepatitis clinical trials

Ziming AN¹,
Qin FENG^{1, 2, 3, 4
, ,}

1.
Institute of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2.
Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
3.
Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China
4.
Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai 201203, China

摘要

摘要: 磁共振质子密度脂肪分数(MRI-PDFF)是一种运用磁共振技术对整个肝脏中的脂肪进行客观定量无创评估的成像方法。主要分析了MRI-PDFF值与“金指标”——非酒精性脂肪性肝炎(NASH)肝组织学评价之间的相关性，探讨其作为NASH临床试验无创性评价指标的优劣。研究表明，MRI-PDFF作为一种新兴的无创技术，适用于定量肝脂肪含量，评价肝脂肪变性程度，但不能替代肝活检作为NASH诊断的工具。同时，药物干预后MRI-PDFF的相对下降不仅与脂肪沉积改善高度相关，而且与炎症和气球样变的改善具有相关性，可以一定程度预测肝组织学的整体改善情况。MRI-PDFF被认为具有作为NASH临床试验替代终点的潜力。
- 非酒精性脂肪性肝炎 /
- 磁共振质子密度脂肪分数 /
- 临床试验
Abstract: Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an imaging method that uses magnetic resonance technology to perform objective, quantitative, and noninvasive assessment of fat in the whole liver. This article mainly analyzes the correlation between MRI-PDFF value and the "gold index" nonalcoholic steatohepatitis (NASH) liver histological evaluation and explores its advantages and disadvantages as a noninvasive evaluation index for NASH clinical trials. Current studies have shown that MRI-PDFF, as an emerging noninvasive technique, is suitable for quantifying liver fat content and evaluating the degree of hepatic steatosis, but it cannot replace liver biopsy as a tool for the diagnosis of NASH. Meanwhile, the relative reduction in MRI-PDFF after drug intervention is not only highly correlated with the improvement of fat deposition, but also correlated with the improvement of inflammation and ballooning degeneration, and MRI-PDFF can predict the overall improvement of liver histology to a certain extent. Therefore, MRI-PDFF is considered a potential surrogate endpoint for NASH clinical trials.
- Non-Alcoholic Steatohepatitis /
- Magnetic Resonance Imaging Proton Density Fat Fraction /
- Clinical Trail

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参考文献(24)

[1]	ZHOU F, ZHOU J, WANG W, et al. Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: A systematic review and Meta-analysis[J]. Hepatology, 2019, 70(4): 1119-1133. DOI: 10.1002/hep.30702.
[2]	Committee of Hepatology, Chinese Research Hospital Association; Fatty Liver Expert Committee, Chinese Medical Doctor Association; National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, et al. Expert recommendations on standardized diagnosis and treatment for fatty liver disease in China (2019 revised edition)[J]. J Clin Hepatol, 2019, 35(11): 2426-2430. DOI: 10.3969/j.issn.1001-5256.2019.11.007. 中国研究型医院学会肝病专业委员会, 中国医师协会脂肪性肝病专家委员会, 中华医学会肝病学分会脂肪肝与酒精性肝病学组, 等. 中国脂肪性肝病诊疗规范化的专家建议(2019年修订版)[J]. 临床肝胆病杂志, 2019, 35(11): 2426-2430. DOI: 10.3969/j.issn.1001-5256.2019.11.007.
[3]	MAO YM. Clinical trials of investigational new drugs for nonalcoholic steatohepatitis: challenges in design and practice[J]. J Clin Hepatol, 2017, 33(12): 2292-2295. DOI: 10.3969/j.issn.1001-5256.2017.12.007. 茅益民. 非酒精性脂肪性肝炎新药临床试验: 设计和实践中的挑战[J]. 临床肝胆病杂志, 2017, 33(12): 2292-2295. DOI: 10.3969/j.issn.1001-5256.2017.12.007.
[4]	CAUSSY C, REEDER SB, SIRLIN CB, et al. Noninvasive, quantitative assessment of liver fat by MRI-PDFF as an endpoint in NASH trials[J]. Hepatology, 2018, 68(2): 763-772. DOI: 10.1002/hep.29797.
[5]	MAMIDIPALLI A, FOWLER KJ, HAMILTON G, et al. Prospective comparison of longitudinal change in hepatic proton density fat fraction (PDFF) estimated by magnitude-based MRI (MRI-M) and complex-based MRI (MRI-C)[J]. Eur Radiol, 2020, 30(9): 5120-5129. DOI: 10.1007/s00330-020-06858-x.
[6]	REEDER SB, CRUITE I, HAMILTON G, et al. Quantitative assessment of liver fat with magnetic resonance imaging and spectroscopy[J]. J Magn Reson Imaging, 2011, 34(4): 729-749. DOI: 10.1002/jmri.22775.
[7]	JIANG LN, ZHAO JM. A clinical trial on the follow-up of nonalcoholic fatty liver disease: An evaluation of pathological endpoint[J]. J Clin Hepatol, 2018, 34(12): 2505-2508. DOI: 10.3969/j.issn.1001-5256.2018.12.004. 蒋丽娜, 赵景民. 跟踪非酒精性脂肪性肝病的临床试验-病理学终点评价[J]. 临床肝胆病杂志, 2018, 34(12): 2505-2508. DOI: 10.3969/j.issn.1001-5256.2018.12.004.
[8]	PIAZZOLLA VA, MANGIA A. Noninvasive diagnosis of NAFLD and NASH[J]. Cells, 2020, 9(4): 1005. DOI: 10.3390/cells9041005.
[9]	GU J, LIU S, DU S, et al. Diagnostic value of MRI-PDFF for hepatic steatosis in patients with non-alcoholic fatty liver disease: A meta-analysis[J]. Eur Radiol, 2019, 29(7): 3564-3573. DOI: 10.1007/s00330-019-06072-4.
[10]	QU Y, LI M, HAMILTON G, et al. Diagnostic accuracy of hepatic proton density fat fraction measured by magnetic resonance imaging for the evaluation of liver steatosis with histology as reference standard: A meta-analysis[J]. Eur Radiol, 2019, 29(10): 5180-5189. DOI: 10.1007/s00330-019-06071-5.
[11]	MIDDLETON MS, HEBA ER, HOOKER CA, et al. Agreement between magnetic resonance imaging proton density fat fraction measurements and pathologist-assigned steatosis grades of liver biopsies from adults with nonalcoholic steatohepatitis[J]. Gastroenterology, 2017, 153(3): 753-761. DOI: 10.1053/j.gastro.2017.06.005.
[12]	TANG A, TAN J, SUN M, et al. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis[J]. Radiology, 2013, 267(2): 422-431. DOI: 10.1148/radiol.12120896.
[13]	PERMUTT Z, LE TA, PETERSON MR, et al. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease-MRI accurately quantifies hepatic steatosis in NAFLD[J]. Aliment Pharmacol Ther, 2012, 36(1): 22-29. DOI: 10.1111/j.1365-2036.2012.05121.x.
[14]	LE TA, CHEN J, CHANGCHIEN C, et al. Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: A randomized controlled trial[J]. Hepatology, 2012, 56(3): 922-932. DOI: 10.1002/hep.25731.
[15]	NOUREDDIN M, LAM J, PETERSON MR, et al. Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials[J]. Hepatology, 2013, 58(6): 1930-1940. DOI: 10.1002/hep.26455.
[16]	LOOMBA R, SIRLIN CB, ANG B, et al. Ezetimibe for the treatment of nonalcoholic steatohepatitis: Assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial)[J]. Hepatology, 2015, 61(4): 1239-1250. DOI: 10.1002/hep.27647.
[17]	JAYAKUMAR S, MIDDLETON MS, LAWITZ EJ, et al. Longitudinal correlations between MRE, MRI-PDFF, and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase Ⅱ trial of selonsertib[J]. J Hepatol, 2019, 70(1): 133-141. DOI: 10.1016/j.jhep.2018.09.024.
[18]	WILDMAN-TOBRINER B, MIDDLETON MM, MOYLAN CA, et al. Association between magnetic resonance imaging-proton density fat fraction and liver histology features in patients with nonalcoholic fatty liver disease or nonalcoholic steatohepatitis[J]. Gastroenterology, 2018, 155(5): 1428-1435.e2. DOI: 10.1053/j.gastro.2018.07.018.
[19]	RINELLA ME, TACKE F, SANYAL AJ, et al. Report on the AASLD/EASL joint workshop on clinical trial endpoints in NAFLD[J]. Hepatology, 2019, 70(4): 1424-1436. DOI: 10.1002/hep.30782.
[20]	PATEL J, BETTENCOURT R, CUI J, et al. Association of noninvasive quantitative decline in liver fat content on MRI with histologic response in nonalcoholic steatohepatitis[J]. Therap Adv Gastroenterol, 2016, 9(5): 692-701. DOI: 10.1177/1756283X16656735.
[21]	LOOMBA R, NEUSCHWANDER-TETRI BA, SANYAL A, et al. Multicenter validation of association between decline in MRI-PDFF and histologic response in NASH[J]. Hepatology, 2020, 72(4): 1219-1229. DOI: 10.1002/hep.31121.
[22]	HARRISON SA, BASHIR MR, GUY CD, et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial[J]. Lancet, 2019, 394(10213): 2012-2024. DOI: 10.1016/S0140-6736(19)32517-6.
[23]	HANNAH WN JR, TORRES DM, HARRISON SA. Nonalcoholic steatohepatitis and endpoints in clinical trials[J]. Gastroenterol Hepatol (NY), 2016, 12(12): 756-763.
[24]	BRIL F, BARB D, LOMONACO R, et al. Change in hepatic fat content measured by MRI does not predict treatment-induced histological improvement of steatohepatitis[J]. J Hepatol, 2020, 72(3): 401-410. DOI: 10.1016/j.jhep.2019.09.018.