Development and validation of an image biomarker to identify metabolic dysfunction associated steatohepatitis: MR-MASH score.

BACKGROUND AND AIMS: Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) requires histology. In this study, a magnetic resonance imaging (MRI) score was developed and validated to identify MASH in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Secondarily, a screening strategy for MASH diagnosis was investigated. METHODS: This prospective multicentre study included 317 patients with biopsy-proven MASLD and contemporaneous MRI. The discovery cohort (Spain, Portugal) included 194 patients. NAFLD activity score (NAS) and fibrosis were assessed with the NASH-CRN histologic system. MASH was defined by the presence of steatosis, lobular inflammation, and ballooning, with NAS ≥4 with or without fibrosis. An MRI-based composite biomarker of Proton Density Fat Fraction and waist circumference (MR-MASH score) was developed. Findings were afterwards validated in an independent cohort (United States, Spain) with different MRI protocols. RESULTS: In the derivation cohort, 51% (n = 99) had MASH. The MR-MASH score identified MASH with an AUC = .88 (95% CI .83-.93) and strongly correlated with NAS (r = .69). The MRI score lower cut-off corresponded to 88% sensitivity with 86% NPV, while the upper cut-off corresponded to 92% specificity with 87% PPV. MR-MASH was validated with an AUC = .86 (95% CI .77-.92), 91% sensitivity (lower cut-off) and 87% specificity (upper cut-off). A two-step screening strategy with sequential MR-MASH examination performed in patients with indeterminate-high FIB-4 or transient elastography showed an 83-84% PPV to identify MASH. The AUC of MR-MASH was significantly higher than that of the FAST score (p < .001). CONCLUSIONS: The MR-MASH score has clinical utility in the identification and management of patients with MASH at risk of progression.

Pancreatic steatosis and iron overload increases cardiovascular risk in non-alcoholic fatty liver disease.

Objective: To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases. Method: A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated. Results: In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis (p<0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits (p<0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD. Conclusion: Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD.

[Three cases of urachal cyst in adults]. / Quistes de uraco en adultos. Presentación de 3 casos y revisión de la literatura.

The urachus is a thick fibrous cord that appears in the fifth month of pregnancy as a result of the allantois obliteration. Urachal cysts occur as a result of a defect in the obliteration of the duct, anomaly detected mainly in children and very rarely in adults. We present three cases of urachal cysts in adults, one of them detected during the study of abdominal pain and the other two, found incidentally during the study of other pathologies. In any case the possibility of urachal cysts was clinically suspected. Histologically, these lesions are lined by epithelium of urothelial type with expression of CK7, CK20, CK5/6, P63 and GATA3. The diagnosis of urachal cysts certainty lies in the histopathological study where the morphology, immunohistochemistry and a proper clinical-pathological correlation, allow to differentiate it from other more frequent abdominal cystic lesions in adults.

Quistes de uraco en adultos. Presentación de 3 casos y revisión de la literatura / Three cases of urachal cyst in adults

El uraco es un grueso cordón fibroso que aparece a partir del quinto mes de gestación como consecuencia de la obliteración de la alantoides. Los quistes de origen uracal se producen como consecuencia de un defecto en la obliteración de dicho conducto, anomalía que se detecta principalmente en niños y raramente en adultos. Presentamos 3 casos de quistes uracales en adultos, uno de ellos detectado durante el estudio de dolor abdominal y los otros 2 hallados de forma incidental durante el estudio de otras patologías. En ningún caso se sospechó clínicamente la posibilidad de quistes uracales. Histológicamente, estas lesiones se encuentran revestidas por epitelio de tipo urotelial con expresión de CK7, CK20, CK5/6, P63 y GATA3. El diagnóstico de certeza recae en el estudio histopatológico donde la morfología, la inmunohistoquímica y un adecuado correlato clínico-patológico, permiten diferenciarlo de otras lesiones quísticas mucho más frecuentes en el adulto.(AU)

The urachus is a thick fibrous cord that appears in the fifth month of pregnancy as a result of the allantois obliteration. Urachal cysts occur as a result of a defect in the obliteration of the duct, anomaly detected mainly in children and very rarely in adults. We present three cases of urachal cysts in adults, one of them detected during the study of abdominal pain and the other two, found incidentally during the study of other pathologies. In any case the possibility of urachal cysts was clinically suspected. Histologically, these lesions are lined by epithelium of urothelial type with expression of CK7, CK20, CK5/6, P63 and GATA3. The diagnosis of urachal cysts certainty lies in the histopathological study where the morphology, immunohistochemistry and a proper clinical-pathological correlation, allow to differentiate it from other more frequent abdominal cystic lesions in adults.(AU)

Automated Whole-Liver MRI Segmentation to Assess Steatosis and Iron Quantification in Chronic Liver Disease.

Background Standardized manual region of interest (ROI) sampling strategies for hepatic MRI steatosis and iron quantification are time consuming, with variable results. Purpose To evaluate the performance of automatic MRI whole-liver segmentation (WLS) for proton density fat fraction (PDFF) and iron estimation (transverse relaxometry [R2*]) versus manual ROI, with liver biopsy as the reference standard. Materials and Methods This prospective, cross-sectional, multicenter study recruited participants with chronic liver disease who underwent liver biopsy and chemical shift-encoded 3.0-T MRI between January 2017 and January 2021. Biopsy evaluation included histologic grading and digital pathology. MRI liver sampling strategies included manual ROI (two observers) and automatic whole-liver (deep learning algorithm) segmentation for PDFF- and R2*-derived measurements. Agreements between segmentation methods were measured using intraclass correlation coefficients (ICCs), and biases were evaluated using Bland-Altman analyses. Linear regression analyses were performed to determine the correlation between measurements and digital pathology. Results A total of 165 participants were included (mean age ± standard deviation, 55 years ± 12; 96 women; 101 of 165 participants [61%] with nonalcoholic fatty liver disease). Agreements between mean measurements were excellent, with ICCs of 0.98 for both PDFF and R2*. The median bias was 0.5% (interquartile range, -0.4% to 1.2%) for PDFF and 2.7 sec-1 (interquartile range, 0.2-5.3 sec-1) for R2* (P < .001 for both). Margins of error were lower for WLS than ROI-derived parameters (-0.03% for PDFF and -0.3 sec-1 for R2*). ROI and WLS showed similar performance for steatosis (ROI AUC, 0.96; WLS AUC, 0.97; P = .53) and iron overload (ROI AUC, 0.85; WLS AUC, 0.83; P = .09). Correlations with digital pathology were high (P < .001) between the fat ratio and PDFF (ROI r = 0.89; WLS r = 0.90) and moderate (P < .001) between the iron ratio and R2* (ROI r = 0.65; WLS r = 0.64). Conclusion Proton density fat fraction and transverse relaxometry measurements derived from MRI automatic whole-liver segmentation (WLS) were accurate for steatosis and iron grading in chronic liver disease and correlated with digital pathology. Automated WLS estimations were higher, with a lower margin of error than manual region of interest estimations. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moura Cunha and Fowler in this issue.

Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease.

Traditional histological evaluation for grading liver disease severity is based on subjective and semi-quantitative scores. We examined the relationship between digital pathology analysis and corresponding scoring systems for the assessment of hepatic necroinflammatory activity. A prospective, multicenter study including 156 patients with chronic liver disease (74% nonalcoholic fatty liver disease-NAFLD, 26% chronic hepatitis-CH etiologies) was performed. Inflammation was graded according to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network system and METAVIR score. Whole-slide digital image analysis based on quantitative (I-score: inflammation ratio) and morphometric (C-score: proportionate area of staining intensities clusters) measurements were independently performed. Our data show that I-scores and C-scores increase with inflammation grades (p < 0.001). High correlation was seen for CH (ρ = 0.85-0.88), but only moderate for NAFLD (ρ = 0.5-0.53). I-score (p = 0.008) and C-score (p = 0.002) were higher for CH than NAFLD. Our MATLAB algorithm performed better than QuPath software for the diagnosis of low-moderate inflammation (p < 0.05). C-score AUC for classifying NASH was 0.75 (95%CI, 0.65-0.84) and for moderate/severe CH was 0.99 (95%CI, 0.97-1.00). Digital pathology measurements increased with fibrosis stages (p < 0.001). In conclusion, quantitative and morphometric metrics of inflammatory burden obtained by digital pathology correlate well with pathologists' scores, showing a higher accuracy for the evaluation of CH than NAFLD.