Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C

Sikorska, Katarzyna; Stalke, Piotr; Romanowski, Tomasz; Rzepko, Robert; Bielawski, Krzysztof Piotr

doi:10.1016/s1499-3872(13)60059-4

Cited by 11 publications

(13 citation statements)

References 41 publications

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“…There were 43 eligible articles with 5,758 cases and 14,741 controls included in our meta-analysis [ 7 , 8 , 10 , 19 , 29 – 67 ], including 16 articles on NAFLD [ 19 , 29 – 43 ], 18 articles on liver cirrhosis [ 7 , 8 , 31 , 44 – 58 ] and 17 articles on HCC [ 7 , 10 , 44 , 46 , 48 , 51 , 52 , 58 – 67 ]. These articles met our inclusion/exclusion criteria.…”

Section: Resultsmentioning

confidence: 99%

“…These articles met our inclusion/exclusion criteria. Thirty-nine studies of high quality (NOS score ≥6) [ 7 , 8 , 10 , 29 – 36 , 38 – 54 , 56 , 58 – 67 ] and 4 studies of moderate quality (NOS score = 6) [ 19 , 37 , 55 , 57 ] were identified. S4 Table presents the summarized characteristics and methodological quality of selected studies, and S5 and S6 Tables show the genotype distributions of the HFE C282Y and H63D polymorphisms in NAFLD, liver cirrhosis and HCC disease.…”

Section: Resultsmentioning

confidence: 99%

“…How can this discrepancy be explained? The follow points were considered: (1) The two articles published by Sikorska K, et al [ 19 ] and Valenti L, et al [ 41 ] after 2011 and an additional three previously undetected articles [ 31 , 34 , 38 ] were added to our meta-analysis. In addition to a population-based control, the data of a hospital-based control were added to enhance the statistical power.…”

Section: Discussionmentioning

confidence: 99%

“…As a key component of iron homeostasis in humans, the HFE protein is linked to the incidence of hereditary hemochromatosis (HH), an autosomal recessive disorder [ 17 , 18 ]. Several common polymorphisms of the HFE gene, such as C282Y (rs1800562), H63D (rs1799945) and S65C (rs1800730), have been reported [ 18 , 19 ]. Accumulating evidence indicates that HFE mutations are associated with susceptibility to many clinical diseases, such as Parkinson's disease (PD) [ 20 ], primary varicose veins [ 21 ] and coronary heart disease (CHD) [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls

Bian

Yin

et al. 2016

PLoS ONE

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BackgroundConflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D) of human HFE (hereditary hemochromatosis) gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and hepatocellular carcinoma (HCC).MethodsAn updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis.ResultsIn total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, Passociation<0.05). However, no significant difference between liver cirrhosis cases and the control group was observed for HFE C282Y and H63D (all Passociation>0.05). In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, Passociation<0.05). Moreover, a positive association between compound heterozygosity for C282Y/H63D and the risk of NAFLD and HCC, but not liver cirrhosis, was observed.ConclusionOur meta-analysis provides evidence that the HFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls

Bian

Yin

et al. 2016

PLoS ONE

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“…[185][186][187][188] In patients with alcoholic and NAFLD, iron overload is frequently present. [185][186][187][188] In patients with alcoholic and NAFLD, iron overload is frequently present.…”

Section: Introductionmentioning

confidence: 99%

Fat and Iron Quantification in the Liver

Yokoo¹,

Browning²

2014

Topics in Magnetic Resonance Imaging

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Liver fat, iron, and combined overload are common manifestations of diffuse liver disease and may cause lipotoxicity and iron toxicity via oxidative hepatocellular injury, leading to progressive fibrosis, cirrhosis, and eventually, liver failure. Intracellular fat and iron cause characteristic changes in the tissue magnetic properties in predictable dose-dependent manners. Using dedicated magnetic resonance pulse sequences and postprocessing algorithms, fat and iron can be objectively quantified on a continuous scale. In this article, we will describe the basic physical principles of magnetic resonance fat and iron quantification and review the imaging techniques of the "past, present, and future." Standardized radiological metrics of fat and iron are introduced for numerical reporting of overload severity, which can be used toward objective diagnosis, grading, and longitudinal disease monitoring. These noninvasive imaging techniques serve an alternative or complimentary role to invasive liver biopsy. Commercial solutions are increasingly available, and liver fat and iron quantitative imaging is now within reach for routine clinical use and may soon become standard of care.

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HNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells

Shi

Wang

Zheng

et al. 2016

Biol Trace Elem Res

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Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4α (HNF-4α) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4α on hepcidin expression was observed by transfecting specific HNF-4α small interfering RNA (siRNA) or plasmids into HepG2 cells. Both direct and indirect mechanisms involved in the regulation of HNF-4α on hepcidin were detected by real-time PCR, Western blotting, chromatin immunoprecipitation (chIP), and reporter genes. It was found that HNF-4α suppressed hepcidin messenger RNA (mRNA) and protein expressions in HepG2 cells, and this suppressive effect was independent of the potential HNF-4α response elements. Phosphorylation of SMAD1 but not STAT3 was inactivated by HNF-4α, and the SMAD4 response element was found essential to HNF-4α-induced hepcidin reduction. Neither inhibitory SMADs, SMAD6, and SMAD7 nor BMPR ligands, BMP2, BMP4, BMP6, and BMP7 were regulated by HNF-4α in HepG2 cells. BMPR1A, but not BMPR1B, BMPR2, ActR2A, ActR2B, or HJV, was decreased by HNF-4α, and HNF4α-knockdown-induced stimulation of hepcidin could be entirely blocked when BMPR1A was interfered with at the same time. In conclusion, the present study suggests that HNF-4α has a suppressive effect on hepcidin expression by inactivating the BMP pathway, specifically via BMPR1A, in HepG2 cells.

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Liver steatosis correlates with iron overload but not with HFE gene mutations in chronic hepatitis C

Cited by 11 publications

References 41 publications

Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls

Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls

Fat and Iron Quantification in the Liver

HNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells

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