Multiparametric Magnetic Resonance Imaging, Autoimmune Hepatitis, and Prediction of Disease Activity.

Noninvasive monitoring of disease activity in autoimmune hepatitis (AIH) has potential advantages for patients for whom liver biopsy is invasive and with risk. We sought to understand the association of multiparametric magnetic resonance imaging (mpMRI) with clinical course of patients with AIH. We prospectively recruited 62 patients (median age, 55 years; 82% women) with clinically confirmed AIH. At recruitment, patients underwent mpMRI with LiverMultiScan alongside clinical investigations, which were repeated after 12-18 months. Associations between iron-corrected T1 (cT1) and other markers of disease were investigated at baseline and at follow-up. Discriminative performance of cT1, liver stiffness, and enhanced liver fibrosis (ELF) to identify those who failed to maintain remission over follow-up was investigated using the areas under the receiver operating characteristic curves (AUCs). Baseline cT1 correlated with alanine aminotransferase (Spearman's correlation coefficient [r S] = 0.28, P = 0.028), aspartate aminotransferase (r S = 0.26, P = 0.038), international normalized ratio (r S = 0.35 P = 0.005), Model for End-Stage Liver Disease (r S = 0.32, P = 0.020), ELF (r S = 0.29, P = 0.022), and liver stiffness r S = 0.51, P < 0.001). After excluding those not in remission at baseline (n = 12), 32% of the remainder failed to maintain remission during follow-up. Failure to maintain remission was associated with significant increases in cT1 over follow-up (AUC, 0.71; 95% confidence interval [CI], 0.52-0.90; P = 0.035) but not with changes in liver stiffness (AUC, 0.68; 95% CI, 0.49-0.87; P = 0.067) or ELF (AUC, 0.57; 95% CI, 0.37-0.78; P = 0.502). cT1 measured at baseline was a significant predictor of future loss of biochemical remission (AUC, 0.68; 95% CI, 0.53-0.83; P = 0.042); neither liver stiffness (AUC, 0.53; 95% CI, 0.34-0.71; P = 0.749) nor ELF (AUC, 0.52; 95% CI, 0.33-0.70; P = 0.843) were significant predictors of loss of biochemical remission. Conclusion: Noninvasive mpMRI has potential to contribute to risk stratification in patients with AIH.

Quantitative multiparametric magnetic resonance imaging can aid non-alcoholic steatohepatitis diagnosis in a Japanese cohort.

BACKGROUND: Non-invasive assessment of non-alcoholic steatohepatitis (NASH) is increasing in desirability due to the invasive nature and costs associated with the current form of assessment; liver biopsy. Quantitative multiparametric magnetic resonance imaging (mpMRI) to measure liver fat (proton density fat fraction) and fibroinflammatory disease [iron-corrected T1 (cT1)], as well as elastography techniques [vibration-controlled transient elastography (VCTE) liver stiffness measure], magnetic resonance elastography (MRE) and 2D Shear-Wave elastography (SWE) to measure stiffness and fat (controlled attenuated parameter, CAP) are emerging alternatives which could be utilised as safe surrogates to liver biopsy. AIM: To evaluate the agreement of non-invasive imaging modalities with liver biopsy, and their subsequent diagnostic accuracy for identifying NASH patients. METHODS: From January 2019 to February 2020, Japanese patients suspected of NASH were recruited onto a prospective, observational study and were screened using non-invasive imaging techniques; mpMRI with LiverMultiScan ®, VCTE, MRE and 2D-SWE. Patients were subsequently biopsied, and samples were scored by three independent pathologists. The diagnostic performances of the non-invasive imaging modalities were assessed using area under receiver operating characteristic curve (AUC) with the median of the histology scores as the gold standard diagnoses. Concordance between all three independent pathologists was further explored using Krippendorff's alpha (a) from weighted kappa statistics. RESULTS: N = 145 patients with mean age of 60 (SD: 13 years.), 39% females, and 40% with body mass index ≥ 30 kg/m2 were included in the analysis. For identifying patients with NASH, MR liver fat and cT1 were the strongest performing individual measures (AUC: 0.80 and 0.75 respectively), and the mpMRI metrics combined (cT1 and MR liver fat) were the overall best non-invasive test (AUC: 0.83). For identifying fibrosis ≥ 1, MRE performed best (AUC: 0.97), compared to VCTE-liver stiffness measure (AUC: 0.94) and 2D-SWE (AUC: 0.94). For assessment of steatosis ≥ 1, MR liver fat was the best performing non-invasive test (AUC: 0.92), compared to controlled attenuated parameter (AUC: 0.75). Assessment of the agreement between pathologists showed that concordance was best for steatosis (a = 0.58), moderate for ballooning (a = 0.40) and fibrosis (a = 0.40), and worst for lobular inflammation (a = 0.11). CONCLUSION: Quantitative mpMRI is an effective alternative to liver biopsy for diagnosing NASH and non-alcoholic fatty liver, and thus may offer clinical utility in patient management.

Correlations Between MRI Biomarkers PDFF and cT1 With Histopathological Features of Non-Alcoholic Steatohepatitis.

Introduction: Late stage clinical trials in non-alcoholic steatohepatitis (NASH) are currently required by the FDA to use liver biopsy as a primary endpoint. The well-reported limitations with biopsy, such as associated risks and sampling error, coupled with patient preference, are driving investigation into non-invasive alternatives. MRI-derived biomarkers proton density fat fraction (PDFF) and iron-corrected T1 mapping (cT1) are gaining traction as emerging alternatives to biopsy for NASH. Our aim was to explore the correlations between cT1 and PDFF (from LiverMultiScan®), with the histological components on the NAFLD-NASH spectrum in a large cohort of cross-sectional data, in order to calibrate the measurement to histology, and to infer what might constitute a clinically meaningful change when related to the FDA's criteria. Materials and Methods: In a retrospective analysis of data combined from three previously published observational NASH studies, in which adult participants who underwent liver biopsy on suspicion of NAFLD or NASH and had an MRI scan measuring cT1 and PDFF (LiverMultiScan®, Perspectum Ltd, UK), associations between imaging biomarkers and histology were tested using Spearman's rank correlation coefficient (rs), and further exploration of the relationships between the imaging variables and histology were performed using linear regression. Results: N = 264 patients with mean age of 54 (SD:9.9), 39% female, and 69% with BMI ≥ 30kg.m-2 were included in the analysis. cT1 and PDFF both correlated with all features of the NAFLD activity score (NAS). cT1 was also positively correlated with Kleiner-Brunt fibrosis. Partial correlations, adjusting for steatosis, revealed cT1 correlated with inflammation and fibrosis, whereas PDFF did not, and both were still associated with the NAS, but correlation was weaker with PDFF than cT1. An estimated difference of 88 ms in cT1, or 21% relative difference in PDFF was related to a two-point difference in overall NAS. Conclusion: The correlations between cT1 and PDFF with the histopathological hallmarks of NASH demonstrate the potential utility of both cT1 and PDFF as non-invasive biomarkers to detect a pharmacodynamic change in NASH, with cT1 showing superiority for detecting changes in inflammation and fibrosis, rather than liver fat alone.