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.

Liver stiffness accuracy by magnetic resonance elastography in histologically proven non-alcoholic fatty liver disease patients: a Spanish cohort.

OBJECTIVES: to evaluate the performance of magnetic resonance elastography (MRE) to stage liver fibrosis in patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and to assess the impact of potential confounding factors in MRE diagnostic accuracy. The secondary objective was to compare MRE with other non-invasive methods for staging fibrosis such as transient elastography (TE) and non-invasive scores (APRI and FIB-4). METHODS: sixty-five histologically confirmed NAFLD patients were prospectively enrolled at the Hospital Universitario Virgen del Rocío (Seville, Spain). Liver stiffness was measured by MRE, TE and non-invasive scores (APRI and FIB-4). Fibrosis was assessed by liver biopsy using the steatosis, activity and fibrosis (SAF) score. Patients were classified into three groups according to the consistency between MRE and histopathological findings: underestimation, concordance and overestimation groups. Areas under the ROC curve (AUROC) and diagnostic performance were evaluated. RESULTS: the area under the ROC curve (AUROC) of MRE in advanced fibrosis (≥ F3) was 0.90 (0.82-0.97), while TE AUROC was 0.82 (0.72-0.93) (p = 0.22) and lower for the non-invasive test (FIB-4 0.67 and APRI 0.62). Inflammatory activity, steatosis grade and higher levels of liver biochemistry appeared to overestimate MRE results in the univariate analysis, but only gamma-glutamyl transferase (GGT) was statistically significant in the multivariate analysis (p < 0.01). Age, sex, body mass index (BMI), weight, diabetes mellitus (DM), high blood pressure (HBP), platelets or lipidic profile did not affect MRE accuracy. CONCLUSIONS: MRE is an effective and non-invasive method for detecting and staging liver fibrosis in NAFLD patients. MRE is more accurate than TE and allows the study of liver anatomy. Histological inflammation and surrogate biomarkers of inflammation can overestimate liver stiffness, but only GGT was statistically significant in the multivariate analysis. Important features of NAFLD patients such as obesity, DM, or lipidic profile did not affect MRE accuracy.

Efficacy and safety of vedolizumab for inflammatory bowel diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vedolizumab is a humanized monoclonal antibody that inhibits gut-selective α4ß7 integrins on the surface of leukocytes, preventing their trafficking into the gastrointestinal tract, and ultimately achieves the effect of suppressing intestinal inflammation. This study aimed to evaluate the efficacy and safety of vedolizumab in the treatment of inflammatory bowel disease. METHODS: After a systematic review of relevant studies, the pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated to evaluate the effect. Heterogeneity was explored using sensitivity analysis, univariate meta-regression, and subgroup analysis. Potential publication bias was evaluated using Egger test and trim-and-fill method. RESULTS: Nine randomized controlled trials involving 4268 participants were included in the meta-analysis. During induction therapy, vedolizumab was more effective than placebo in treating active ulcerative colitis and Crohn disease in terms of clinical response (RR = 1.55, 95%CI: 1.35-1.78), clinical remission (RR = 1.90, 95%CI: 1.50-2.41), and mucosal healing (RR = 1.53, 95%CI: 1.21-1.95). A superior effect in terms of durable Clinical or Crohn disease Activity Index-100 response (RR = 1.65, 95%CI: 1.20-2.26), clinical remission (RR = 1.92, 95%CI: 1.48-2.50), and glucocorticoid-free remission (RR = 2.22, 95%CI: 1.71-2.90) was found during maintenance treatment. Vedolizumab was not associated with any adverse events and was as safe as placebo in terms of the risk of serious adverse reactions. CONCLUSIONS: Vedolizumab may be safe and effective as an induction and maintenance therapy for the treatment of inflammatory bowel disease; however, further studies are needed to validate this conclusion.

Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). METHODS: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. RESULTS: A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively. CONCLUSION: Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.