Change in MRI-PDFF and Histologic Response in Patients With Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis

• Published in: Clinical gastroenterology and hepatology Vol. 19; no. 11; pp. 2274 - 2283.e5
• Main Authors: Stine, Jonathan G., Munaganuru, Nagambika, Barnard, Abbey, Wang, Jennifer L., Kaulback, Kellee, Argo, Curtis K., Singh, Siddarth, Fowler, Kathryn J., Sirlin, Claude B., Loomba, Rohit
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2021
• Subjects: Adult; Biomarkers; Clinical Trial; Female; Histology; Humans; Liver; Liver Biopsy; Magnetic Resonance Imaging; Male; Middle Aged; Non-alcoholic Fatty Liver Disease - diagnostic imaging; Protons; Steatohepatitis; Steatosis; NAS; FDA; NAFLD; OR; Clinical Trial; Liver Biopsy; MRI; CI; Histology; NASH; Steatosis; PDFF; Steatohepatitis
• ISSN: 1542-3565; 1542-7714
• DOI: 10.1016/j.cgh.2020.08.061

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. 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. 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. 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.