Jonathan G Stine1, Nagambika Munaganuru2, Abbey Barnard3, Jennifer L Wang4, Kellee Kaulback5, Curtis K Argo6, Siddarth Singh3, Kathryn J Fowler7, Claude B Sirlin7, Rohit Loomba8. 1. Division of Gastroenterology and Hepatology, Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Department of Public Health Sciences, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Liver Center, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Cancer Institute, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania. 2. Department of Medicine, University of California, San Diego, La Jolla, California. 3. Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, California. 4. Division of Gastroenterology and Hepatology, Department of Medicine, University of Chicago, Chicago, Illinois. 5. Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania. 6. Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia, Charlottesville, Virginia. 7. Liver Imaging Group, Department of Radiology, University of California, San Diego, La Jolla, California. 8. Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, La Jolla, California; Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, California; NAFLD Research Center, University of California, San Diego, La Jolla, California. Electronic address: roloomba@ucsd.edu.
Abstract
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.
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.
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