医学
内科学
血色病
遗传性血色病
肝硬化
肝活检
胃肠病学
瞬态弹性成像
代谢综合征
铁蛋白
等位基因
肝病
活检
生物
肥胖
遗传学
基因
作者
Deepika Suresh,Anming Li,Matthew J. Miller,Karn Wijarnpreecha,Vincent Chen
摘要
Abstract Background & Aims Ferritin has been investigated as a biomarker for liver fibrosis and iron in patients with metabolic dysfunction‐associated steatotic liver disease (MASLD). However, whether metabolic hyperferritinaemia predicts progression of liver disease remains unknown. In this study, we sought to understand associations between hyperferritinaemia and (1) adverse clinical outcomes and (2) common genetic variants related to iron metabolism and liver fibrosis. Methods This was a retrospective analysis of adults with MASLD seen at the University of Michigan Health System, where MASLD was defined by hepatic steatosis on imaging, biopsy or vibration‐controlled transient elastography, plus metabolic risk factors in the absence of chronic liver diseases other than hemochromatosis. The primary predictor was serum ferritin level, which was dichotomized based on a cut‐off of 300 or 450 mcg/L for women or men. Primary outcomes included (1) incident cirrhosis, liver‐related events, congestive heart failure (CHF), and mortality and (2) distribution of common genetic variants associated with hepatic fibrosis and hereditary hemochromatosis. Results Of 7333 patients with MASLD, 1468 (20%) had elevated ferritin. In multivariate analysis, ferritinaemia was associated with increased mortality (HR 1.68 [1.35–2.09], p < .001) and incident liver‐related events (HR 1.92 [1.11–3.32], p = .019). Furthermore, elevated ferritin was associated with carriage of cirrhosis‐promoting alleles including PNPLA3 ‐rs738409‐G allele ( p = .0068) and TM6SF2 ‐rs58542926‐T allele ( p = 0.0083) but not with common HFE mutations. Conclusions In MASLD patients, metabolic hyperferritinaemia was associated with increased mortality and higher incidence of liver‐related events, and cirrhosis‐promoting alleles but not with iron overload‐promoting HFE mutations.
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