TY - JOUR
T1 - Change in MRI-PDFF and Histologic Response in Patients With Nonalcoholic Steatohepatitis
T2 - A Systematic Review and Meta-Analysis
AU - Stine, Jonathan G.
AU - Munaganuru, Nagambika
AU - Barnard, Abbey
AU - Wang, Jennifer L.
AU - Kaulback, Kellee
AU - Argo, Curtis K.
AU - Singh, Siddarth
AU - Fowler, Kathryn J.
AU - Sirlin, Claude B.
AU - Loomba, Rohit
N1 - Funding Information:
Funding This study was supported by National Institutes of Health (HIH) grant L30 DK118601 (to Jonathan G. Stine); NIH/ National Institute of Diabetes and Digestive and Kidney Diseases grants R01DK12378 , U01DK61734 , R01DK106419 ; Department of Defense Peer-Reviewed Cancer Research Program CA170674P2; and NIH/ National Institute of Environmental Health Sciences 5P42ES010337 (to Rohit Loomba).
Funding Information:
Funding This study was supported by National Institutes of Health (HIH) grant L30 DK118601 (to Jonathan G. Stine); NIH/National Institute of Diabetes and Digestive and Kidney Diseases grants R01DK12378, U01DK61734, R01DK106419; Department of Defense Peer-Reviewed Cancer Research Program CA170674P2; and NIH/National Institute of Environmental Health Sciences 5P42ES010337 (to Rohit Loomba). Conflicts of Interest These authors disclose the following: Jonathan G. Stine has received research funding from Target Pharma. Kathryn J. Fowler has received grant support from Bayer, GE, and Siemens; and served as a consultant for Innovis. Claude B. Sirlin has received grants from GE, Siemens, Philips, Bayer, and Gilead; has received personal fees from Wolters Kluwer for educational royalties outside the submitted work; has received personal fees for consultation from Blade, Boehringer Ingelheim, and Epigenomics; has served as a consultant under the auspices of the his institution for AMRA, Bristol-Myers Squibb, Exact Sciences, GE Digital, and IBM-Watson; and has lab service agreements from Enanta, Gilead, ICON, Intercept, Nusirt, Shire, Synageva, and Takeda. Rohit Loomba has served as a consultant or advisory board member for Arrowhead Pharmaceuticals, AstraZeneca, Bird Rock Bio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cirius, CohBar, Conatus, Eli Lilly, Galmed, Gemphire, Gilead, Glympse bio, GNI, GRI Bio, Intercept, Ionis, Janssen, Merck, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prometheus, Sanofi, Siemens, and Viking Therapeutics; his institution has received grant support from Allergan, Boehringer Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, GE, Genfit, Gilead, Intercept, Grail, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, NuSirt, Pfizer, pH Pharma, Prometheus, and Siemens; and he is co-founder of Liponexus. The remaining authors disclose no conflicts.
Publisher Copyright:
© 2021 AGA Institute
PY - 2021/11
Y1 - 2021/11
N2 - Background & Aims: Magnetic resonance imaging proton density fat fraction (MRI-PDFF) offers promise as a non-invasive biomarker of treatment response in early-phase nonalcoholic steatohepatitis (NASH) trials. We performed a systematic review to quantify the association between a ≥ 30% reduction in MRI-PDFF and histologic response in NASH. Methods: We searched the Cochrane Library, Embase, Medline and trial registries through May 2020 for early-phase clinical trials that incorporated MRI-PDFF and examined histologic response following intervention in adults with NASH. Subjects were classified as MRI-PDFF responders (relative decline in liver fat ≥30%) or non-responders (relative decline in liver fat <30%). MRI-PDFF responders versus non-responders were compared. Primary outcome was histologic response defined as a 2-point improvement in NAFLD Activity Score with at least 1-point improvement in lobular inflammation or ballooning. Secondary outcome was NASH resolution. Proportions and random effects odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. Results: Seven studies met inclusion criteria, comprising 346 subjects (median age 51 years; 59% female; 46% with diabetes). MRI-PDFF responders were significantly more likely to have a histologic response (51% vs 14%, P < .001; OR 6.98, 95% CI 2.38-20.43, P < .001) and NASH resolution (41% vs 7%, P < .001; OR 5.45, 95% CI 1.53-19.46, P = .009) compared to non-responders. Conclusions: This meta-analysis demonstrates that a ≥30% relative decline in MRI-PDFF is associated with higher odds of histologic response and NASH resolution. These results support the use of MRI-PDFF in non-invasive monitoring of treatment response in early-phase NASH clinical trials and provide helpful data for sample-size estimation for histology-based assessment.
AB - Background & Aims: Magnetic resonance imaging proton density fat fraction (MRI-PDFF) offers promise as a non-invasive biomarker of treatment response in early-phase nonalcoholic steatohepatitis (NASH) trials. We performed a systematic review to quantify the association between a ≥ 30% reduction in MRI-PDFF and histologic response in NASH. Methods: We searched the Cochrane Library, Embase, Medline and trial registries through May 2020 for early-phase clinical trials that incorporated MRI-PDFF and examined histologic response following intervention in adults with NASH. Subjects were classified as MRI-PDFF responders (relative decline in liver fat ≥30%) or non-responders (relative decline in liver fat <30%). MRI-PDFF responders versus non-responders were compared. Primary outcome was histologic response defined as a 2-point improvement in NAFLD Activity Score with at least 1-point improvement in lobular inflammation or ballooning. Secondary outcome was NASH resolution. Proportions and random effects odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. Results: Seven studies met inclusion criteria, comprising 346 subjects (median age 51 years; 59% female; 46% with diabetes). MRI-PDFF responders were significantly more likely to have a histologic response (51% vs 14%, P < .001; OR 6.98, 95% CI 2.38-20.43, P < .001) and NASH resolution (41% vs 7%, P < .001; OR 5.45, 95% CI 1.53-19.46, P = .009) compared to non-responders. Conclusions: This meta-analysis demonstrates that a ≥30% relative decline in MRI-PDFF is associated with higher odds of histologic response and NASH resolution. These results support the use of MRI-PDFF in non-invasive monitoring of treatment response in early-phase NASH clinical trials and provide helpful data for sample-size estimation for histology-based assessment.
UR - http://www.scopus.com/inward/record.url?scp=85101885475&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101885475&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2020.08.061
DO - 10.1016/j.cgh.2020.08.061
M3 - Review article
C2 - 32882428
AN - SCOPUS:85101885475
SN - 1542-3565
VL - 19
SP - 2274-2283.e5
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 11
ER -