Decreases in cT1 and liver fat content reflect treatment-induced histological improvements in MASH.

BACKGROUND & AIMS: MRI biomarkers of liver disease are robust and reproducible alternatives to liver biopsy. Emerging data suggest that absolute reduction in iron corrected T1 (cT1) of ≥ 80 ms and relative reduction in liver fat content of 30% reflect histological improvement. We aimed to validate the associations of changes to these noninvasive biomarkers with histological improvement, specifically the resolution of steatohepatitis. METHODS: A retrospective analysis of participants from three interventional clinical trials who underwent multiparametric MRI to measure liver cT1 and liver fat content (LFC) (LiverMultiScan) alongside biopsies at baseline and end of study. Responders were defined as those achieving resolution of steatohepatitis with no worsening in fibrosis. Differences in the magnitude of change in cT1 and LFC between responders and non-responders was assessed. RESULTS: Individual patient data from 150 participants were included. There was a significant decrease in liver cT1 (-119 ms vs. -49 ms) and liver fat content (-65% vs. -29%) in responders compared to non-responders (P < .001) respectively. The diagnostic accuracy to identify responders was 0.72 (AUC) for both. The Youden's index for cT1 to separate responders from non-responders was -82 ms and for liver fat was a 58% relative reduction. Those achieving a ≥ 80 ms reduction in cT1 were 5-times more likely to achieve histological response (sens 0.68; spec 0.70). Those achieving a 30% relative reduction in liver fat were ∼4 times more likely to achieve a histological response (sens 0.77; spec 0.53). CONCLUSIONS: These results, from three combined drug trials, demonstrate that changes in multiparametric MRI markers of liver health (cT1 and PDFF) can predict histological response for steatohepatitis following therapeutic intervention. IMPACT AND IMPLICATIONS: There is great interest in identifying suitable biomarkers that can be used to replace liver biopsy, or to identify those patients who would benefit from one, in both the clinical management of MASH and in drug development. We investigated the utility of two MRI-derived non-invasive tests, iron corrected T1 mapping (cT1) and liver fat content from proton density fat fraction (PDFF), to predict histological improvement in patients who had undergone experimental treatment for MASH. Using data from 150 people who participated in one of three clinical trials, we observed that a reduction in cT1 by over 80 ms and a relative reduction in PDFF of over 58% were the optimal thresholds for change that predicted resolution of steatohepatitis. PDFF as a marker of liver fat, and cT1 as a specific measure of liver disease activity, are both effective at identifying those who are likely responding to drug interventions and experiencing improvements in overall liver health. CLINICAL TRIAL NUMBER(S): NCT02443116, NCT03976401, NCT03551522.

MRI-serum-based score accurately identifies patients undergoing liver transplant without rejection avoiding the need for liver biopsy: A multisite European study.

Serum liver tests (serum tests) and histological assessment for T-cell-mediated rejection are essential for post-liver transplant monitoring. Liver biopsy carries a risk of complications that are preferably avoided in low-risk patients. Multiparametric magnetic resonance imaging (mpMRI) is a reliable noninvasive diagnostic method that quantifies liver disease activity and has prognostic utility. Our aim was to determine whether using mpMRI in combination with serum tests could noninvasively identify low-risk patients who underwent liver transplants who are eligible to avoid invasive liver biopsies. In a multicenter prospective study (RADIcAL2), including 131 adult and pediatric (children and adolescent) patients with previous liver transplants from the Netherlands, Portugal, and the United Kingdom, concomitant mpMRI and liver biopsies were performed. Biopsies were centrally read by 2 expert pathologists. T-cell-mediated rejection was assessed using the BANFF global assessment. Diagnostic accuracy to discriminate no rejection versus indeterminate or T-cell-mediated liver transplant rejection was performed using the area under the receiver operating characteristic curve. In this study, 52% of patients received a routine (protocol) biopsy, while 48% had a biopsy for suspicion of pathology. Thirty-eight percent of patients had no rejection, while 62% had either indeterminate (21%) or T-cell-mediated rejection (41%). However, there was a high interobserver variability (0 < Cohen's Kappa < 0.85) across all histology scores. The combined score of mpMRI and serum tests had area under the receiver operating characteristic curve 0.7 (negative predictive value 0.8) to identify those without either indeterminate or T-cell-mediated rejection. Combining both imaging and serum biomarkers into a composite biomarker (imaging and serum biomarkers) has the potential to monitor the liver graft to effectively risk stratify patients and identify those most likely to benefit from a noninvasive diagnostic approach, reducing the need for liver biopsy.

Quantitative MRI for Monitoring Metabolic Dysfunction-Associated Steatotic Liver Disease: A Test-Retest Repeatability Study.

BACKGROUND: Quantitative magnetic resonance imaging metrics iron-corrected T1 (cT1) and liver fat from proton density fat-fraction (PDFF) are both commonly used as noninvasive biomarkers for metabolic dysfunction-associated steatohepatitis (MASH); however, their repeatability in this population has rarely been characterized. PURPOSE: To quantify the variability of cT1 and liver fat fraction from PDFF in patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH. STUDY TYPE: Prospective, single center. POPULATION: Twenty-one participants (female = 11, mean age 53 ± 24 years) with biopsy-confirmed MASLD, including 6 with MASH and fibrosis ≥2. FIELD STRENGTH/SEQUENCE: 3 T; T1 and T2* mapping for the generation of cT1 (shMOLLI: CardioMaps and 2D MDE, T1map-FIESTA and LMS MOST: StarMap, 2D Multi-Echo FSPGR) and magnitude-only PDFF sequence for liver fat quantification (LMS IDEAL: StarMap, 2D Multi-Echo FSPGR). ASSESSMENT: T1 mapping and PDFF scans were performed twice on the same day for all participants (N = 21), with an additional scan 2-4 weeks later for MASH patients with fibrosis ≥2 (N = 6). Whole liver segmentation masks were generated semi-automatically and average pixel counts within these masks were used for the calculation of cT1 and liver fat fraction. STATISTICAL TESTS: Bland-Altman analysis for repeatability coefficient (RC) and 95% limits of agreement (LOA) and intraclass correlation coefficient (ICC). RESULTS: Same-day RC was 32.1 msec (95% LOA: -36.6 to 24.2 msec) for cT1 and 0.6% (95% LOA: -0.5% to 0.7%) for liver fat fraction; the ICCs were 0.98 (0.96-0.99) and 1.0, respectively. Short-term RC was 65.2 msec (95% LOA: -63.8 to 76.5 msec) for cT1 and 2.6% (95% LOA: -2.8% to 3.1%) for liver fat fraction. DATA CONCLUSION: In participants with MASLD and MASH, cT1 and liver fat fraction measurements show excellent test-retest repeatability, supporting their use in monitoring MASLD and MASH. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Multiparametric Magnetic Resonance Imaging and Magnetic Resonance Elastography to Evaluate the Early Effects of Bariatric Surgery on Nonalcoholic Fatty Liver Disease.

Background: Bariatric surgery is the most effective treatment for morbid obesity and reduces the severity of nonalcoholic fatty liver disease (NAFLD) in the long term. Less is known about the effects of bariatric surgery on liver fat, inflammation, and fibrosis during the early stages following bariatric surgery. Aims: This exploratory study utilises advanced imaging methods to investigate NAFLD and fibrosis changes during the early metabolic transitional period following bariatric surgery. Methods: Nine participants with morbid obesity underwent sleeve gastrectomy. Multiparametric MRI (mpMRI) and magnetic resonance elastography (MRE) were performed at baseline, during the immediate (1 month), and late (6 months) postsurgery period. Liver fat was measured using proton density fat fraction (PDFF), disease activity using iron-correct T1 (cT1), and liver stiffness using MRE. Repeated measured ANOVA was used to assess longitudinal changes and Dunnett's method for multiple comparisons. Results: All participants (Age 45.1 ± 9.0 years, BMI 39.7 ± 5.3 kg/m2) had elevated hepatic steatosis at baseline (PDFF >5%). In the immediate postsurgery period, PDFF decreased significantly from 14.1 ± 7.4% to 8.9 ± 4.4% (p = 0.016) and cT1 from 826.9 ± 80.6 ms to 768.4 ± 50.9 ms (p = 0.047). These improvements continued to the later postsurgery period. Bariatric surgery did not reduce liver stiffness measurements. Conclusion: Our findings support using MRI as a noninvasive tool to monitor NAFLD in patient with morbid obesity during the early stages following bariatric surgery.

Comparison between magnetic resonance and ultrasound-derived indicators of hepatic steatosis in a pooled NAFLD cohort.

BACKGROUND & AIMS: MRI-based proton density fat fraction (PDFF) and the ultrasound-derived controlled attenuation parameter (CAP) are non-invasive techniques for quantifying liver fat, which can be used to assess steatosis in patients with non-alcoholic fatty liver disease (NAFLD). This study compared both of these techniques to histopathological graded steatosis for the assessment of fat levels in a large pooled NAFLD cohort. METHODS: This retrospective study pooled N = 581 participants from two suspected NAFLD cohorts (mean age (SD) 56 (12.7), 60% females). Steatosis was graded according to NASH-CRN criteria. Liver fat was measured non-invasively using PDFF (with Liver MultiScan's Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation method, LMS-IDEAL, Perspectum, Oxford) and CAP (FibroScan, Echosens, France), and their diagnostic performances were compared. RESULTS: LMS-IDEAL and CAP detected steatosis grade ≥ 1 with AUROCs of 1.00 (95% CI, 0.99-1.0) and 0.95 (95% CI, 0.91-0.99), respectively. LMS-IDEAL was superior to CAP for detecting steatosis grade ≥ 2 with AUROCs of 0.77 (95% CI, 0.73-0.82] and 0.60 (95% CI, 0.55-0.65), respectively. Similarly, LMS-IDEAL outperformed CAP for detecting steatosis grade ≥ 3 with AUROCs of 0.81 (95% CI, 0.76-0.87) and 0.63 (95% CI, 0.56-0.70), respectively. CONCLUSION: LMS-IDEAL was able to diagnose individuals accurately across the spectrum of histological steatosis grades. CAP performed well in identifying individuals with lower levels of fat (steatosis grade ≥1); however, its diagnostic performance was inferior to LMS-IDEAL for higher levels of fat (steatosis grades ≥2 and ≥3). TRIAL REGISTRATION: ClinicalTrials.gov (NCT03551522); https://clinicaltrials.gov/ct2/show/NCT03551522. UMIN Clinical Trials Registry (UMIN000026145); https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026145.