Kalutkiewicz, Kyle

Background and Aims: The presence of at-risk NASH is associated with an increased risk of cirrhosis and complications. Therefore, noninvasive identification of at-risk NASH with an accurate biomarker is a critical need for pharmacologic therapy. We aim to explore the performance of several magnetic resonance (MR)-based imaging parameters in diagnosing at-risk NASH. Approach and Results: This prospective clinical trial (NCT02565446) includes 104 paired MR examinations and liver biopsies performed in patients with suspected or diagnosed NAFLD. Magnetic resonance elastography-assessed liver stiffness (LS), 6-point Dixon-derived proton density fat fraction (PDFF), and single-point saturation-recovery acquisition-calculated T1 relaxation time were explored. Among all predictors, LS showed the significantly highest accuracy in diagnosing at-risk NASH [AUCLS: 0.89 (0.82, 0.95), AUCPDFF: 0.70 (0.58, 0.81), AUCT1: 0.72 (0.61, 0.82), z-score test z >1.96 for LS vs any of others]. The optimal cutoff value of LS to identify at-risk NASH patients was 3.3 kPa (sensitivity: 79%, specificity: 82%, negative predictive value: 91%), whereas the optimal cutoff value of T1 was 850 ms (sensitivity: 75%, specificity: 63%, and negative predictive value: 87%). PDFF had the highest performance in diagnosing NASH with any fibrosis stage [AUCPDFF: 0.82 (0.72, 0.91), AUCLS: 0.73 (0.63, 0.84), AUCT1: 0.72 (0.61, 0.83), |z| <1.96 for all]. Conclusion: Magnetic resonance elastography-assessed LS alone outperformed PDFF, and T1 in identifying patients with at-risk NASH for therapeutic trials.

Abstract Background and Aims Despite that hepatic fibrosis often affects the liver globally, spatial distribution can be heterogeneous. This study aimed to investigate the effect of liver stiffness (LS) heterogeneity on concordance between MR elastography (MRE)‐based fibrosis staging and biopsy staging in patients with NAFLD. Approach and Results We retrospectively evaluated data from 155 NAFLD patients who underwent liver biopsy and 3 Tesla MRE and undertook a retrospective validation study of 169 NAFLD patients at three hepatology centers. Heterogeneity of stiffness was assessed by measuring the range between minimum and maximum MRE‐based LS measurement (LSM). Variability of LSM was defined as the stiffness range divided by the maximum stiffness value. The cohort was divided into two groups (homogenous or heterogeneous), according to whether variability was below or above the average for the training cohort. Based on histopathology and receiver operating characteristic (ROC) analysis, optimum LSM thresholds were determined for MRE‐based fibrosis staging of stage 4 (4.43, kPa; AUROC, 0.89) and stage ≥3 (3.93, kPa; AUROC, 0.89). In total, 53 had LSM above the threshold for stage 4. Within this group, 30 had a biopsy stage of <4. In 86.7% of these discordant cases, variability of LSM was classified as heterogeneous. In MRE‐based LSM stage ≥3, 88.9% of discordant cases were classified as heterogeneous. Results of the validation cohort were similar to those of the training cohort. Conclusions Discordance between biopsy‐ and MRE‐based fibrosis staging is associated with heterogeneity in LSM, as depicted with MRE.