Hepatic iron is the major determinant of serum ferritin in NAFLD patients

Abstract

Background and Aims Elevated serum ferritin is common in NAFLD, and is associated with more advanced disease and increased mortality. Hyperferritinaemia in NAFLD is often attributed to inflammation, while in other conditions ferritin closely reflects body iron stores. The aim of this study was to clarify the underlying cause of hyperferritinaemia in NAFLD. Methods Ferritin levels were examined with markers of iron status, inflammation and liver injury across the clinical spectrum of NAFLD using blood, tissue and magnetic resonance (MR) imaging. A separate larger group of NAFLD patients with hepatic iron staining and quantification were used for validation. Results Serum ferritin correlated closely with the iron regulatory hormone hepcidin, and liver iron levels determined by MR. Furthermore, ferritin levels reflected lower serum adiponectin, a marker of insulin resistance, and liver fat, but not cytokine or CRP levels. Ferritin levels differed according to fibrosis stage, increasing from early to moderate disease, and declining in cirrhosis. A similar pattern was found in the validation cohort of NAFLD patients, where ferritin levels were highest in those with macrophage iron deposition. Multivariate analysis revealed liver iron and hepcidin levels as the major determinants of serum ferritin. Conclusions While hyperferritinaemia is associated with markers of liver injury and insulin resistance, serum hepcidin and hepatic iron are the strongest predictors of ferritin levels. These findings highlight the role of disordered iron homeostasis in the pathogenesis of NAFLD, suggesting that therapies aimed at correcting iron metabolism may be beneficial.

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

“…Contrary to our findings, a number of other studies have indicated a positive association between serum adiponectin and measures of human iron stores 9, 37, 38. These studies may be limited by the choice of surrogate for HIC.…”

“…Our data showed that despite strong statistical significance ( P < 0.001), the association itself was not strong ( r 2 = 0.17), indicating that only 17% of the variance in serum ferritin is attributable to HIC. Ryan et al38 have recently reported an inverse association between liver iron and serum adiponectin. However, the MRI T2* values, used as an inverse surrogate for HIC, were not corrected for volume of hepatic steatosis.…”

Liver R2* is affected by both iron and fat: A dual biopsy‐validated study of chronic liver disease

“…These patients typically have a very high LIC of 10–30 mg/g; in contrast, typical chronic liver disease (CLD) patients referred to a hepatology department are expected to have a much lower LIC of around or below 1.2 mg/g, which is considered the upper limit of normal LIC . Later work has studied R2* in other patient groups with lower levels of LIC, although few studies have compared R2* to both histology and quantitative elemental analysis of LIC …”

“…13 Later work has studied R2* in other patient groups with lower levels of LIC, although few studies have compared R2* to both histology and quantitative elemental analysis of LIC. [14][15][16][17][18] Recently, both Mamidipalli et al 19 and Bashir et al 20 reported that fat accumulation in the liver correlates with a slight increase in liver R2*. Although the exact mechanism is unknown, Mamidipalli et al hypothesized that, similar to iron, hepatic fat droplets induce local susceptibility effects, leading to an increased R2*.…”

Pathomorphological analysis of nonalcohoholic and alcoholic steathohepatitis adverse consequences

“…В таких случаях у больных АСГ и НАСГ при УЗИ обращало внимание нали-чие гиперэхогенных очагов в ткани печени, а в лабораторных исследованиях выявлялись повы-шенные уровни сывороточного железа (более 30,43 мкмоль/л) и ферритина (более 250 мкг/л). По литературным данным у больных НАЖБП нередко отмечается повышение уровня сыворо-точного ферритина, тесно связанного с отложе-нием железа в печени, что сильно коррелирует с инсулин-резистентностью, более развитым фиб-розом и повышенной смертностью пациентов [30,31]. Депонирование железа в ретикулоэндоте-лиальных клетках печени при НАЖБП взаимос-вязано с развитым фиброзом [3].…”