Association between pattern of hepatic iron deposition and severity of MASH among patients enrolled in the NASH Clinical Research Network

Abstract

Background: We previously showed that the pattern of liver biopsy iron staining is associated with metabolic dysfunction-associated steatohepatitis (MASH) severity and fibrosis. The goal of the current study was to further examine the relationships between hepatic iron deposition and disease severity in a large biopsy-proven cohort of nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Methods: Adult patients enrolled in the NASH CRN Non-alcoholic Fatty Liver Disease (NAFLD) Database, PIVENS, or FLINT studies from November 2004 to May 2022 were included. Patient demographics, clinical, and laboratory data were compared between patients with different iron deposition patterns. Multivariate logistic regression analysis was performed to identify the relationship between the iron deposition pattern and advanced fibrosis. Results: A total of 2833 patients were included; 1166 patients (41%) had positive hepatic iron staining. Two hundred seventy-two (9.6%) patients had hepatocellular (HC) iron, 284 (10%) had iron in the reticuloendothelial system (RES), and the remaining (21.4%) had mixed iron deposition. A higher proportion of patients with RES iron had grade 3 steatosis (29%), severe hepatocyte ballooning (47%), severe lobular inflammation (15%), cirrhosis (16%), and definite MASH (71%). On multivariate regression analysis, patients with RES iron had higher odds of advanced fibrosis (adjusted OR: 1.34, 95% CI: 1.11-1.62, p=0.003), while patients with HC iron had lower odds of advanced fibrosis (aOR: 0.68, 95% CI: 0.55-0.83, p<0.001). Conclusions: Hepatic iron is common in patients with MASH. Patients with a RES iron pattern have a severe disease, while those with HC iron have milder disease. These data provide insights into the potential role of hepatic iron in the pathogenesis of MASH.