Fluorescent Egg White-Based Carbon Dots as a High-Sensitivity Iron Chelator for the Therapy of Nonalcoholic Fatty Liver Disease by Iron Overload in Zebrafish

Background & Aims: Mild iron overload is frequently reported in patients with nonalcoholic fatty liver disease (NAFLD). Hepcidin is the master iron-regulatory peptide and hemojuvelin (HJV) is the key regulator of iron-dependent secretion of hepcidin. The aims of this study were to evaluate serum HJV and hepcidin levels in patients with biopsy-proven NAFLD with and without hepatic iron overload, and to identify potential associations of HJV and hepcidin with the clinical characteristics of the patients enrolled. Methods: Serum levels of HJV and hepcidin were measured in 66 NAFLD patients with (n=12) and without (n=54) iron overload, and controls (n=35) by enzyme-linked immunosorbent assay. Hemojuvelin and hepcidin levels were assessed in relation to clinical characteristics and liver histologic evaluation of the participants. Results: Significantly lower serum HJV (281.1 [239.2-353.6] vs. 584.8 [440.3-661] ng/ml, p<0.001) and similar serum hepcidin levels (60.5±31.1 vs. 55.8±11.9 ng/ml, p=0.285) were found in NAFLD patients when compared to controls. İron-overloaded NAFLD patients had significantly lower HJV (249.9 [187.6-296.3] vs. 292.9 [243-435] ng/ml, p=0.032) and significantly higher hepcidin (78.4±35.5 vs. 56.5±28.9ng/ml, p=0.027) levels than NAFLD patients without iron overload. Fibrosis stage was significantly higher in iron overloaded NAFLD group (p<0.001). Ferritin levels correlated significantly both with HOMA-IR (r=0.368, p=0.002) and fibrosis stage (r=0.571, p<0.001). Conclusions: Our findings suggest that HJV levels are low in NAFLD and even lower in iron overloaded NAFLD, while hepcidin levels are higher in NAFLD with iron overload. The gradually decreased HJV and increased hepcidin concentrations in our patients most likely reflect the physiological response to iron accumulation in the liver.

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Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

Diagnostics ◽

10.3390/diagnostics10080579 ◽

2020 ◽

Vol 10 (8) ◽

pp. 579 ◽

Cited By ~ 3

Author(s):

Yoshio Sumida ◽

Masashi Yoneda ◽

Yuya Seko ◽

Hiroshi Ishiba ◽

Tasuku Hara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

High Sensitivity ◽

Cost Effective ◽

Abdominal Ultrasound ◽

Screening Tests ◽

Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability.

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Iron-Overload Evaluation by Noninvasive Methods in Patients with Nonalcoholic Fatty Liver Disease, Overweight, and Hyperferritinemia

Diabetes ◽

10.2337/db18-292-lb ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 292-LB ◽

Cited By ~ 1

Author(s):

PAULA P.F. BRANISSO ◽

CLAUDIA P. OLIVEIRA ◽

HILTON M. LEÃO FILHO ◽

ARITANIA SANTOS ◽

FABIANA R. LIMA ◽

...

Keyword(s):

Liver Disease ◽

Iron Overload ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Noninvasive Methods ◽

Nonalcoholic Fatty Liver

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Hyperferritinemia in Nonalcoholic Fatty Liver Disease: Iron Accumulation or Inflammation?

Seminars in Liver Disease ◽

10.1055/s-0039-1693114 ◽

2019 ◽

Vol 39 (04) ◽

pp. 476-482

Author(s):

Wenke Moris ◽

Pauline Verhaegh ◽

Daisy Jonkers ◽

Cees van Deursen ◽

Ger Koek

Keyword(s):

Liver Disease ◽

Iron Overload ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Lifestyle Changes ◽

Iron Accumulation ◽

Cochrane Library ◽

Nonalcoholic Fatty Liver ◽

The Cochrane Library

AbstractHyperferritinemia, observed in inflammation, iron overload as well as in combination of both, is found in ∼30% of nonalcoholic fatty liver disease (NAFLD) patients. The authors summarized the evidence regarding the potential cause of hyperferritinemia in NAFLD, as this may affect the indicated therapy. A systematic literature search was conducted in EMBASE, PubMed, MEDLINE, and the Cochrane library. In the majority of NAFLD patients, hyperferritinemia is due to inflammation without hepatic iron overload. In a smaller group, a dysmetabolic iron overload syndrome (DIOS) is found, showing hyperferritinemia in combination with mild iron accumulation in the reticuloendothelial cells. The smallest group consists of NAFLD patients with hemochromatosis. Phlebotomy is only effective with hepatocellular iron overload and should not be the treatment when hyperferritinemia is related to inflammation, whether or not combined with DIOS. Treatment with lifestyle changes is to date probably the more effective way until new medication is becoming available.

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