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.

Differential Outcomes and Clinical Challenges of NAFLD With Extreme Obesity.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. The prevalence of extreme obesity, defined as body mass index (BMI) of 50 kg/m2 or higher, is rising more rapidly than overall obesity. We aimed to compare the clinical outcomes and performance of noninvasive fibrosis assessment tools in NAFLD with or without extreme obesity. A retrospective analysis was performed in 304 patients with NAFLD with extreme obesity and compared them to patients with NAFLD with BMI of 40 kg/m2 or less, matched for age, gender, race, and liver fibrosis stage. The mean age of the NAFLD with extreme obesity cohort was 55.9 years, BMI 55 kg/m2, and 49.7% had cirrhosis at initial evaluation. Baseline cirrhosis and coronary artery disease were associated with increased risk of death, and dyslipidemia with decreased risk of mortality. Age, insulin use, hypertension, albumin and platelet count were associated with cirrhosis. Fifteen percent of patients had weight-loss surgery, but this was not associated with survival or risk of cirrhosis. Of the 850 abdominal ultrasound scans performed in 255 patients, 24.1% were deemed suboptimal for hepatocellular carcinoma screening. The mean NAFLD fibrosis score (NFS) in the extreme obesity cohort, versus a propensity-matched cohort with BMI of 40 kg/m2 or less, was significantly different for both low fibrosis (F0-F2) (0.222 vs. -1.682, P < 0.0001) and high fibrosis (F3-F4) (2.216 vs. 0.557, P < 0.001). Conclusion: NAFLD with extreme obesity is associated with increased risk of liver-related and overall mortality. Accurate noninvasive assessment of liver fibrosis, low rates of weight loss surgery, and high failure rate of ultrasound were identified as clinical challenges in this population.

A Celiac Disease Phenotype After Checkpoint Inhibitor Exposure: An Example of Immune Dysregulation After Immunotherapy.

Celiac disease is characterized by duodenal inflammation after exposure to gluten. Checkpoint inhibitors are antibodies that inhibit the inhibitory signals of the cytotoxic T lymphocytes to enhance antitumor responses. A 79-year-old man with an unknown history of celiac disease underwent treatment with pembrolizumab for recurrent left maxillary melanoma. He subsequently developed diarrhea and weight loss. Serology was positive for anti-tissue transglutaminase immunoglobulin A. Upper endoscopy revealed duodenal villous atrophy, which was confirmed on biopsy. A gluten-free diet was not tolerated, and symptoms resolved with withdrawal of pembrolizumab and steroid administration for another medical reason.