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 elastography (MRE) and transient elastography (TE) are noninvasive techniques for detection of liver fibrosis. Single-center studies have compared the diagnostic performance of MRE vs TE in patients with nonalcoholic fatty liver disease (NAFLD). We conducted a pooled analysis of individual participant data from published studies to compare the diagnostic performance of MRE vs TE for staging of liver fibrosis in patients with NAFLD, using liver biopsy as reference.

Methods

We performed a systematic search of publication databases, from 2005 through 2017. We identified 3 studies of adults with NAFLD who were assessed by MRE, TE, and liver biopsy. In a pooled analysis, we calculated the cluster-adjusted area under the curve (AUROC) of MRE and TE for the detection of each stage of fibrosis. AUROC comparisons between MRE and TE were performed using the Delong test.

Results

Our pooled analysis included 230 participants with biopsy-proven NAFLD with mean age of 52.2±13.9 years and a body mass index of 31.9±7.5 kg/m2. The proportions of patients with fibrosis of stages 0, 1, 2, 3, and 4 were: 31.7%, 27.8%, 15.7%, 13.9%, and 10.9%, respectively. The AUROC of TE vs MRE for detection of fibrosis stages ≥1 was 0.82 (95% CI, 0.76-0.88) vs 0.87 (95% CI, 0.82-0.91) (P=.04); for stage≥ 2 was 0.87 (95% CI, 0.82-0.91) vs 0.92 (95% CI, 0.88-0.96) (P=.03); for stage ≥3 was 0.84 (95% CI, 0.78-0.90) vs 0.93 (95% CI, 0.89-0.96) (P=.001); for stage ≥ 4 was 0.84 (95% CI, 0.73-0.94) vs 0.94 (95% CI, 0.89-0.99) (P=.005).

Conclusion

In a pooled analysis of data from individual participants with biopsy-proven NAFLD, we found MRE to have a statistically significantly higher diagnostic accuracy than TE in detection of each stage of fibrosis. MRE and TE each have roles in detection of fibrosis in patients with NAFLD, depending upon the level of accuracy desired.