Role of serum uric acid and ferritin in the development and progression of NAFLD

International Journal of Molecular Sciences

Volumn 17, Issue 4, 2016, Pages

  Lombardi, Rosa ^a   Pisano, Giuseppina ^a   Fargion, Silvia ^a  

^a FONDAZIONE IRCCS CA GRANDA OSPEDALE MAGGIORE POLICLINICO   (Italy)

Author keywords

Fibrosis; Insulin resistance; Liver damage; Metabolic syndrome; NASH; Oxidative stress; Serum markers; SUA

Indexed keywords

CRYOPYRIN; FERRITIN; FRUCTOSE; INSULIN; INSULIN RECEPTOR SUBSTRATE 1; INTERLEUKIN 18; INTERLEUKIN 1BETA; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; URIC ACID;

ADIPOSE TISSUE; DISEASE SEVERITY; DYSLIPIDEMIA; DYSMETABOLIC IRON OVERLOAD SYNDROME; FERRITIN BLOOD LEVEL; HEMOCHROMATOSIS; HUMAN; HYPERFERRITINEMIA; HYPERURICEMIA; INSULIN RESISTANCE; IRON DEPLETION; IRON OVERLOAD; LIPID DIET; LIPID METABOLISM; LIPID STORAGE; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONALCOHOLIC FATTY LIVER DISEASE ACTIVITY SCORE; NONHUMAN; OBESITY; OXIDATIVE STRESS; PROTEIN PHOSPHORYLATION; REVIEW; RISK FACTOR; UNFOLDED PROTEIN RESPONSE; URIC ACID BLOOD LEVEL; BLOOD; DISEASE COURSE; LIVER CIRRHOSIS; PATHOLOGY;

DISEASE PROGRESSION; FERRITINS; HUMANS; LIVER CIRRHOSIS; METABOLIC SYNDROME X; NON-ALCOHOLIC FATTY LIVER DISEASE; URIC ACID;

EID: 84963781575     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms17040548     Document Type: Review

References (85)

1. Williams, C.D.; Stengel, J.; Asike, M.I.; Torres, D.M.; Shaw, J.; Contreras, M.; Landt, C.L.; Harrison, S.A. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study. Gastroenterology 2011, 140, 124-131. [CrossRef] [PubMed]
2. Lonardo, A.; Ballestri, S.; Marchesini, G.; Angulo, P.; Loria, P. Nonalcoholic fatty liver disease: A precursor of the metabolic syndrome. Dig. Liver Dis. 2015, 47, 181-190. [CrossRef] [PubMed]
3. Anstee, Q.M.; Targher, G.; Day, C.P. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat. Rev. Gastroenterol. Hepatol. 2013, 10, 330-344. [CrossRef] [PubMed]
4. Serfaty, L.; Lemoine, M. Definition and natural history of metabolic steatosis: Clinical aspects of NAFLD, NASH and cirrhosis. Diabetes Metab. 2008, 34, 634-637. [CrossRef]
5. Buzzetti, E.; Lombardi, R.; de Luca, L.; Tsochatzis, E.A. Noninvasive assessment of fibrosis in patients with nonalcoholic fatty liver disease. Int. J. Endocrinol. 2015, 2015, 343828. [CrossRef] [PubMed]
6. Tsochatzis, E.A.; Gurusamy, K.S.; Ntaoula, S.; Cholongitas, E.; Davidson, B.R.; Burroughs, A.K. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: A meta-analysis of diagnostic accuracy. J. Hepatol. 2011, 54, 650-659. [CrossRef] [PubMed]
7. Mount, D.B.; Kwon, C.Y.; Zandi-Nejad, K. Renal urate transport. Rheum. Dis. Clin. N. Am. 2006, 32, 313-331. [CrossRef] [PubMed]
8. Richette, P.; Bardin, T. Gout. Lancet 2010, 375, 318-328. [CrossRef]
9. Zhang, M.L.; Gao, Y.X.; Wang, X.; Chang, H.; Huang, G.W. Serum uric acid and appropriate cutoff value for prediction of metabolic syndrome among Chinese adults. J. Clin. Biochem. Nutr. 2013, 52, 38-42. [CrossRef] [PubMed]
10. Choi, H.K.; Ford, E.S. Prevalence of the metabolic syndrome in individuals with hyperuricemia. Am. J. Med. 2007, 120, 442-447. [CrossRef] [PubMed]
11. Kodama, S.; Saito, K.; Yachi, Y.; Asumi, M.; Sugawara, A.; Totsuka, K.; Saito, A.; Sone, H. Association between serum uric acid and development of type 2 diabetes. Diabetes Care 2009, 32, 1737-1742. [CrossRef] [PubMed]
12. Lin, S.D.; Tsai, D.H.; Hsu, S.R. Association between serum uric acid level and components of the metabolic syndrome. J. Chin. Med. Assoc. 2006, 69, 512-516. [CrossRef]
13. Lv, Q.; Meng, X.F.; He, F.F.; Chen, S.; Su, H.; Xiong, J.; Gao, P.; Tian, X.J.; Liu, J.S.; Zhu, Z.H.; et al. High serum uric acid and increased risk of type 2 diabetes: A systemic review and meta-analysis of prospective cohort studies. PLoS ONE 2013, 8, e56864.
14. Lonardo, A.; Loria, P.; Leonardi, F.; Borsatti, A.; Neri, P.; Pulvirenti, M.; Verrone, A.M.; Bagni, A.; Bertolotti, M.; Ganazzi, D.; et al. Fasting insulin and uric acid levels but not indices of iron metabolism are independent predictors of non-alcoholic fatty liver disease. A case-control study. Dig. Liver Dis. 2002, 34, 204-211. [CrossRef]
15. Li, Y.; Xu, C.; Yu, C.; Xu, L.; Miao, M. Association of serum uric acid level with non-alcoholic fatty liver disease: A cross-sectional study. J. Hepatol. 2009, 50, 1029-1034. [PubMed]
16. Ryu, S.; Chang, Y.; Kim, S.G.; Cho, J.; Guallar, E. Serum uric acid levels predict incident nonalcoholic fatty liver disease in healthy Korean men. Metabolism 2011, 60, 860-866. [CrossRef] [PubMed]
17. Liu, Z.; Que, S.; Zhou, L.; Zheng, S. Dose-response relationship of serum uric acid with metabolic syndrome and non-alcoholic fatty liver disease incidence: A meta-analysis of prospective studies. Sci. Rep. 2015, 5, 14325. [CrossRef] [PubMed]
18. Yuan, H.; Yu, C.; Li, X.; Sun, L.; Zhu, X.; Zhao, C.; Zhang, Z.; Yang, Z. Serum uric acid levels and risk of metabolic syndrome: A dose-response meta-analysis of prospective studies. J. Clin. Endocrinol. Metab. 2015, 100, 4198-4207. [CrossRef] [PubMed]
19. Chen, J.H.; Chuang, S.Y.; Chen, H.J.; Yeh, W.T.; Pan, W.H. Serum uric acid level as an independent risk factor for all-cause, cardiovascular, and ischemic stroke mortality: A Chinese cohort study. Arthritis Rheum. 2009, 61, 225-232. [CrossRef] [PubMed]
20. Xu, C.; Wan, X.; Xu, L.; Weng, H.; Yan, M.; Miao, M.; Sun, Y.; Xu, G.; Dooley, S.; Li, Y.; et al. Xanthine oxidase in non-alcoholic fatty liver disease and hyperuricemia: One stone hits two birds. J. Hepatol. 2015, 62, 1412-1419. [CrossRef] [PubMed]
21. Sirota, J.C.; McFann, K.; Targher, G.; Johnson, R.J.; Chonchol, M.; Jalal, D.I. Elevated serum uric acid levels are associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in the United States: Liver ultrasound data from the National Health and Nutrition Examination Survey. Metabolism 2013, 62, 392-399. [CrossRef] [PubMed]
22. Petta, S.; Camma, C.; Cabibi, D.; Di Marco, V.; Craxi, A. Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 2011, 34, 757-766. [PubMed]
23. Afzali, A.; Weiss, N.S.; Boyko, E.J.; Ioannou, G.N. Association between serum uric acid level and chronic liver disease in the United States. Hepatology 2010, 52, 578-589. [CrossRef] [PubMed]
24. Abreu, E.; Fonseca, M.J.; Santos, A.C. Association between hyperuricemia and insulin resistance. Acta Med. Port. 2011, 24, 565-574. [PubMed]
25. Tan, Y.; Liu, X.; Zhou, K.; He, X.; Lu, C.; He, B.; Niu, X.; Xiao, C.; Xu, G.; Bian, Z.; et al. The potential biomarkers to identify the development of steatosis in hyperuricemia. PLoS ONE 2016, 11, e0149043.
26. Li, C.; Hsieh, M.C.; Chang, S.J. Metabolic syndrome, diabetes, and hyperuricemia. Curr. Opin. Rheumatol. 2013, 25, 210-216. [CrossRef] [PubMed]
27. Zhu, Y.; Hu, Y.; Huang, T.; Zhang, Y.; Li, Z.; Luo, C.; Luo, Y.; Yuan, H.; Hisatome, I.; Yamamoto, T; et al. High uric acid directly inhibits insulin signalling and induces insulin resistance. Biochem. Biophys. Res. Commun. 2014, 447, 707-714. [CrossRef] [PubMed]
28. Vandanmagsar, B.; Youm, Y.H.; Ravussin, A.; Galgani, J.E.; Stadler, K.; Mynatt, R.L.; Ravussin, E.; Stephens, J.M.; Dixit, V.D. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med. 2011, 17, 179-188. [CrossRef] [PubMed]
29. Lanaspa, M.A.; Sanchez-Lozada, L.G.; Choi, Y.J.; Cicerchi, C.; Kanbay, M.; Roncal-Jimenez, C.A.; Ishimoto, T.; Li, N.; Marek, G.; Duranay, M et al. Uric acid induces hepatic steatosis by generation of mitochondrial oxidative stress: potential role in fructose-dependent and -independent fatty liver. J. Biol. Chem. 2012, 287, 40732-40744. [CrossRef] [PubMed]
30. Choi, Y.J.; Shin, H.S.; Choi, H.S.; Park, J.W.; Jo, I.; Oh, E.S.; Lee, K.Y.; Lee, B.H.; Johnson, R.J.; Kang, D.H. Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab. Investig. 2014, 94, 1114-1125. [CrossRef] [PubMed]
31. Wan, X.; Xu, C.; Lin, Y.; Lu, C.; Li, D.; Sang, J.; He, H.; Liu, X.; Li, Y.; Yu, C. Uric acid regulates hepatic steatosis and insulin resistance through the NLRP3 inflammasome-dependent mechanism. J. Hepatol. 2015. [CrossRef]
32. Ackerman, Z.; Oron-Herman, M.; Grozovski, M.; Rosenthal, T.; Pappo, O.; Link, G.; Sela, B.A. Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction. Hypertension 2005, 45, 1012-1018. [CrossRef] [PubMed]
33. Lanaspa, M.A.; Sanchez-Lozada, L.G.; Cicerchi, C.; Li, N.; Roncal-Jimenez, C.A.; Ishimoto, T.; Le, M.; Garcia, G.E.; Thomas, J.B.; Rivard, C.J et al. Uric acid stimulates fructokinase and accelerates fructose metabolism in the development of fatty liver. PLoS ONE 2012, 7, e47948. [CrossRef] [PubMed]
34. Pagliassotti, M.J. Endoplasmic reticulum stress in nonalcoholic fatty liver disease. Annu. Rev. Nutr. 2012, 32, 17-33. [CrossRef] [PubMed]
35. Zhang, C.; Chen, X.; Zhu, R.M.; Zhang, Y.; Yu, T.; Wang, H.; Zhao, H.; Zhao, M.; Ji, Y.L.; Chen, Y.H et al. Endoplasmic reticulum stress is involved in hepatic SREBP-1c activation and lipid accumulation in fructose-fed mice. Toxicol. Lett. 2012, 212, 229-240. [CrossRef] [PubMed]
36. De Oliveira, E.P.; Burini, R.C. High plasma uric acid concentration: causes and consequences. Diabetol. Metab. Syndr. 2012, 4, 12. [CrossRef] [PubMed]
37. Martinon, F.; Petrilli, V.; Mayor, A.; Tardivel, A.; Tschopp, J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006, 440, 237-241. [CrossRef] [PubMed]
38. Bugianesi, E.; Manzini, P.; D’Antico, S.; Vanni, E.; Longo, F.; Leone, N.; Massarenti, P.; Piga, A.; Marchesini, G.; Rizzetto, M. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 2004, 39, 179-187. [CrossRef] [PubMed]
39. Fernandez-Real, J.M.; Ricart-Engel, W.; Arroyo, E.; Balanca, R.; Casamitjana-Abella, R.; Cabrero, D.; Fernandez-Castaner, M.; Soler, J. Serum ferritin as a component of the insulin resistance syndrome. Diabetes Care 1998, 21, 62-68. [CrossRef] [PubMed]
40. Ford, E.S.; Cogswell, M.E. Diabetes and serum ferritin concentration among U.S. adults. Diabetes Care 1999, 22, 1978-1983. [CrossRef] [PubMed]
41. Salonen, J.T.; Tuomainen, T.P.; Nyyssonen, K.; Lakka, H.M.; Punnonen, K. Relation between iron stores and non-insulin dependent diabetes in men: Case-control study. BMJ 1998, 317, 727. [CrossRef] [PubMed]
42. Kim, C.W.; Chang, Y.; Sung, E.; Shin, H.; Ryu, S. Serum ferritin levels predict incident non-alcoholic fatty liver disease in healthy Korean men. Metabolism 2012, 61, 1182-1188. [CrossRef] [PubMed]
43. Gillum, R.F. Association of serum ferritin and indices of body fat distribution and obesity in Mexican American men—The third national health and nutrition examination survey. Int. J. Obes. Relat. Metab. Disord. 2001, 25, 639-645. [CrossRef] [PubMed]
44. Piperno, A.; Trombini, P.; Gelosa, M.; Mauri, V.; Pecci, V.; Vergani, A.; Salvioni, A.; Mariani, R.; Mancia, G. Increased serum ferritin is common in men with essential hypertension. J. Hypertens. 2002, 20, 1513-1518. [CrossRef] [PubMed]
45. Williams, M.J.; Poulton, R.; Williams, S. Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women. Atherosclerosis 2002, 165, 179-184. [CrossRef]
46. Iwasaki, T.; Nakajima, A.; Yoneda, M.; Yamada, Y.; Mukasa, K.; Fujita, K.; Fujisawa, N.; Wada, K.; Terauchi, Y. Serum ferritin is associated with visceral fat area and subcutaneous fat area. Diabetes Care 2005, 28, 2486-2491. [CrossRef] [PubMed]
47. Alam, F.; Memon, A.S.; Fatima, S.S. Increased Body Mass Index may lead to Hyperferritinemia Irrespective of Body Iron Stores. Pak. J. Med. Sci. 2015, 31, 1521-1526. [PubMed]
48. Ellervik, C.; Marott, J.L.; Tybjaerg-Hansen, A.; Schnohr, P.; Nordestgaard, B.G. Total and cause-specific mortality by moderately and markedly increased ferritin concentrations: General population study and metaanalysis. Clin. Chem. 2014, 60, 1419-1428. [CrossRef] [PubMed]
49. Fernandez-Real, J.M.; Lopez-Bermejo, A.; Ricart, W. Cross-talk between iron metabolism and diabetes. Diabetes 2002, 51, 2348-2354. [CrossRef] [PubMed]
50. Zelber-Sagi, S.; Nitzan-Kaluski, D.; Halpern, Z.; Oren, R. NAFLD and hyperinsulinemia are major deter4.minants of serum ferritin levels. J. Hepatol. 2007, 46, 700-707. [CrossRef] [PubMed]
51. Moirand, R.; Mortaji, A.M.; Loreal, O.; Paillard, F.; Brissot, P.; Deugnier, Y. A new syndrome of liver iron overload with normal transferrin saturation. Lancet 1997, 349, 95-97. [CrossRef]
52. Corradini, E.; Meynard, D; Wu, Q.; Chen, S.; Ventura, P.; Pietrangelo, A.; Babitt, J.L. Serum and liver iron differently regulate the bone morphogenetic protein 6 (BMP6)-SMAD signaling pathway in mice. Hepatology 2011, 54, 273-284. [CrossRef] [PubMed]
53. Vecchi, C.; Montosi, G.; Zhang, K.; Lamberti, I.; Duncan, S.A.; Kaufman, R.J.; Pietrangelo, A. ER stress controls iron metabolism through induction of hepcidin. Science 2009, 325, 877-880. [CrossRef] [PubMed]
54. Fargion, S.; Valenti, L.; Fracanzani, A.L. Beyond hereditary hemochromatosis: New insights into the relationship between iron overload and chronic liver diseases. Dig. Liver Dis. 2011, 43, 89-95. [CrossRef] [PubMed]
55. Murotomi, K.; Arai, S.; Uchida, S.; Endo, S.; Mitsuzumi, H.; Tabei, Y.; Yoshida, Y.; Nakajima, Y. Involvement of splenic iron accumulation in the development of nonalcoholic steatohepatitis in Tsumura Suzuki Obese Diabetes mice. Sci. Rep. 2016, 6, 22476. [CrossRef] [PubMed]
56. Corradini, E.; Pietrangelo, A. Iron and steatohepatitis. J. Gastroenterol. Hepatol. 2012, 27, 42-46. [CrossRef] [PubMed]
57. Dongiovanni, P.; Fracanzani, A.L.; Fargion, S.; Valenti, L. Iron in fatty liver and in the metabolic syndrome: a promising therapeutic target. J. Hepatol. 2011, 55, 920-932. [CrossRef] [PubMed]
58. Boga, S.; Alkim, H.; Alkim, C.; Koksal, A.R.; Bayram, M.; Yilmaz Ozguven, M.B.; Tekin Neijmann, S. The relationship of serum hemojuvelin and hepcidin levels with iron overload in nonalcoholic fatty liver disease. J. Gastrointest. Liver Dis. 2015, 24, 293-300.
59. Senates, E.; Yilmaz, Y.; Colak, Y.; Ozturk, O.; Altunoz, M.E.; Kurt, R.; Ozkara, S.; Aksaray, S.; Tuncer, I.; Ovunc, A.O. Serum levels of hepcidin in patients with biopsy-proven nonalcoholic fatty liver disease. Metab. Syndr. Relat. Disord. 2011, 9, 287-290. [CrossRef] [PubMed]
60. Demircioglu, F.; Gorunmez, G.; Dagistan, E.; Goksugur, S.B.; Bekdas, M.; Tosun, M.; Kizildag, B.; Kismet, E. Serum hepcidin levels and iron metabolism in obese children with and without fatty liver: Case-control study. Eur. J. Pediatr. 2014, 173, 947-951. [CrossRef] [PubMed]
61. Neri, S.; Pulvirenti, D.; Signorelli, S.; Ignaccolo, L.; Tsami, A.; Mauceri, B.; Misseri, M.; Interlandi, D.; Cutuli, N.; Castellino, P. The HFE gene heterozygosis H63D: A cofactor for liver damage in patients with steatohepatitis? Epidemiological and clinical considerations. Intern. Med. J. 2008, 38, 254-258. [CrossRef] [PubMed]
62. Valenti, L.; Dongiovanni, P.; Fracanzani, A.L.; Fargion, S. HFE mutations in nonalcoholic fatty liver disease. Hepatology 2008, 47, 1794-1795. [CrossRef] [PubMed]
63. McClain, D.A.; Abraham, D.; Rogers, J.; Brady, R.; Gault, P.; Ajioka, R.; Kushner, J.P. High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis. Diabetologia 2006, 49, 1661-1669. [CrossRef] [PubMed]
64. Choi, J.S.; Koh, I.U.; Lee, H.J.; Kim, W.H.; Song, J. Effects of excess dietary iron and fat on glucose and lipid metabolism. J. Nutr. Biochem. 2013, 24, 1634-1644. [CrossRef] [PubMed]
65. Dongiovanni, P.; Ruscica, M.; Rametta, R.; Recalcati, S.; Steffani, L.; Gatti, S.; Girelli, D.; Cairo, G.; Magni, P.; Fargion, S et al. Dietary iron overload induces visceral adipose tissue insulin resistance. Am. J. Pathol. 2013, 182, 2254-2263. [CrossRef] [PubMed]
66. Vecchi, C.; Montosi, G.; Garuti, C.; Corradini, E.; Sabelli, M.; Canali, S.; Pietrangelo, A. Gluconeogenic signals regulate iron homeostasis via hepcidin in mice. Gastroenterology 2014, 146, 1060-1069. [CrossRef] [PubMed]
67. Marra, F.; Bertolani, C. Adipokines in liver diseases. Hepatology 2009, 50, 957-969. [CrossRef] [PubMed]
68. Bekri, S.; Gual, P.; Anty, R.; Luciani, N.; Dahman, M.; Ramesh, B.; Iannelli, A.; Staccini-Myx, A.; Casanova, D.; Ben Amor, I et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006, 131, 788-796. [CrossRef] [PubMed]
69. Green, A.; Basile, R.; Rumberger, J.M. Transferrin and iron induce insulin resistance of glucose transport in adipocytes. Metabolism 2006, 55, 1042-1045. [CrossRef] [PubMed]
70. Item, F.; Konrad, D. Visceral fat and metabolic inflammation: the portal theory revisited. Obes. Rev. 2012, 13, 30-39. [CrossRef] [PubMed]
71. Fargion, S.; Mattioli, M.; Fracanzani, A.L.; Sampietro, M.; Tavazzi, D.; Fociani, P.; Taioli, E.; Valenti, L.; Fiorelli, G. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am. J. Gastroenterol. 2001, 96, 2448-2455. [CrossRef] [PubMed]
72. Manousou, P.; Kalambokis, G.; Grillo, F.; Watkins, J.; Xirouchakis, E.; Pleguezuelo, M.; Leandro, G.; Arvaniti, V.; Germani, G.; Patch, D et al. Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients. Liver Int. 2011, 31, 730-739. [CrossRef] [PubMed]
73. Kowdley, K.V.; Belt, P.; Wilson, L.A.; Yeh, M.M.; Neuschwander-Tetri, B.A.; Chalasani, N.; Sanyal, A.J.; Nelson, J.E.; Network, N.C.R. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2012, 55, 77-85. [CrossRef] [PubMed]
74. Kim, Y.S.; Jung, E.S.; Hur, W.; Bae, S.H.; Choi, J.Y.; Song, M.J.; Kim, C.W.; Jo, S.H.; Lee, C.D.; Lee, Y.S et al. Noninvasive predictors of nonalcoholic steatohepatitis in Korean patients with histologically proven nonalcoholic fatty liver disease. Clin. Mol. Hepatol. 2013, 19, 120-130. [CrossRef] [PubMed]
75. Angulo, P.; George, J.; Day, C.P.; Vanni, E.; Russell, L.; de la Cruz, A.C.; Liaquat, H.; Mezzabotta, L.; Lee, E.; Bugianesi, E. Serum ferritin levels lack diagnostic accuracy for liver fibrosis in patients with nonalcoholic fatty liver disease. Clin. Gastroenterol. Hepatol. 2014, 12, 1163-1169. [CrossRef] [PubMed]
76. Yoneda, M.; Thomas, E.; Sumida, Y.; Imajo, K.; Eguchi, Y.; Hyogo, H.; Fujii, H.; Ono, M.; Kawaguchi, T.; Schiff, E.R. Clinical usage of serum ferritin to assess liver fibrosis in patients with non-alcoholic fatty liver disease: Proceed with caution. Hepatol. Res. 2014, 44, E499-E502. [CrossRef] [PubMed]
77. Nakamura, A.; Yoneda, M.; Sumida, Y.; Eguchi, Y.; Fujii, H.; Hyogo, H.; Ono, M.; Suzuki, Y.; Kawaguchi, T.; Aoki, N et al. Modification of a simple clinical scoring system as a diagnostic screening tool for non-alcoholic steatohepatitis in Japanese patients with non-alcoholic fatty liver disease. J. Diabetes Investig. 2013, 4, 651-658. [CrossRef] [PubMed]
78. Cales, P.; Boursier, J.; Oberti, F.; Hubert, I.; Gallois, Y.; Rousselet, M.C.; Dib, N.; Moal, V.; Macchi, L.; Chevailler, A et al. FibroMeters: A family of blood tests for liver fibrosis. Gastroenterol. Clin. Biol. 2008, 32, 40-51. [CrossRef]
79. Valenti, L.; Canavesi, E.; Galmozzi, E.; Dongiovanni, P.; Rametta, R.; Maggioni, P.; Maggioni, M.; Fracanzani, A.L.; Fargion, S. β-Globin mutations are associated with parenchymal siderosis and fibrosis in patients with non-alcoholic fatty liver disease. J. Hepatol. 2010, 53, 927-933. [CrossRef] [PubMed]
80. Facchini, F.S.; Hua, N.W.; Stoohs, R.A. Effect of iron depletion in carbohydrate-intolerant patients with clinical evidence of nonalcoholic fatty liver disease. Gastroenterology 2002, 122, 931-939. [CrossRef] [PubMed]
81. Fernandez-Real, J.M.; Penarroja, G.; Castro, A.; Garcia-Bragado, F.; Hernandez-Aguado, I.; Ricart, W. Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and β-cell function. Diabetes 2002, 51, 1000-1004. [CrossRef] [PubMed]
82. Valenti, L.; Fracanzani, A.L.; Dongiovanni, P.; Bugianesi, E.; Marchesini, G.; Manzini, P.; Vanni, E.; Fargion, S. Iron depletion by phlebotomy improves insulin resistance in patients with nonalcoholic fatty liver disease and hyperferritinemia: evidence from a case-control study. Am. J. Gastroenterol. 2007, 102, 1251-1258. [CrossRef] [PubMed]
83. Chen, S.C.; Huang, Y.F.; Wang, J.D. Hyperferritinemia and hyperuricemia may be associated with liver function abnormality in obese adolescents. PLoS ONE 2012, 7, e48645. [CrossRef] [PubMed]
84. Ghio, A.J.; Ford, E.S.; Kennedy, T.P.; Hoidal, J.R. The association between serum ferritin and uric acid in humans. Free Radic. Res. 2005, 39, 337-342. [CrossRef] [PubMed]
85. Mainous, A.G; Knoll, M.E.; Everett, C.J.; Matheson, E.M.; Hulihan, M.M.; Grant, A.M. Uric acid as a potential cue to screen for iron overload. J. Am. Board Fam. Med. 2011, 24, 415-421. [CrossRef] [PubMed]