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Journals / Aydın Sağlık Dergisi / 2026 / Cilt: 11 Sayı: 1

HEMOCHROMATOSIS AND HEPATOCELLULAR CARCINOMA

Merve Çiğdem Özgel(İSTANBUL ÜNİVERSİTESİ, SAĞLIK BİLİMLERİ ENSTİTÜSÜ, KANSER GENETİĞİ (DR))0000-0002-3014-0843
Buğra Tuncer(İSTANBUL ÜNİVERSİTESİ, ONKOLOJİ ENSTİTÜSÜ)0000-0001-8023-3223
Pages
1–31
Publication Date
2025-02-28
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

This review focuses on the relationship between hemochromatosis, a rare disorder that is among the risk factors, and hepatocellular carcinoma.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:An autosomal recessive iron overload condition called hemochromatosis is typified by enhanced dietary iron sorption and hepatic iron buildup.
📊
Key Findings & Data:It is a risk agent for hepatocellular carcinoma since it is a prevalent illness in the European population.
💡
Conclusion & Impact:This review focuses on the relationship between hemochromatosis, a rare disorder that is among the risk factors, and hepatocellular carcinoma.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Hemochromatosis · Hepatocellular carcinoma · HFE gene

Abstract

An autosomal recessive iron overload condition called hemochromatosis is typified by enhanced dietary iron sorption and hepatic iron buildup. It is a risk agent for hepatocellular carcinoma since it is a prevalent illness in the European population. One of the tumors that is most common and deadly around the globe, particularly in Asia, is hepatocellular carcinoma. Because it is often detected in its advanced stages, hepatocellular carcinoma has a weak prognosis. Early tumor detection improves the chances of a successful cure and a longer life. Because of this, the EASL (European Association for the Study of the Liver) instructions support liver tumor screening using ultrasound scanning every six months, regardless of liver condition. This review focuses on the relationship between hemochromatosis, a rare disorder that is among the risk factors, and hepatocellular carcinoma.

🔖

Cite This Article

Özgel, M. Ç., Tuncer, B. (2025). HEMOCHROMATOSIS AND HEPATOCELLULAR CARCINOMA. Aydın Sağlık Dergisi, Cilt: 11 Sayı: 1, 1–31. https://ajindex.com/articles/1458595

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References (68)

  1. Adams, P. C. (2023). Hepatocellular Carcinoma in Hemochromatosis: Where or When? Dig Dis Sci, 68(1), 12-13. https://doi.org/10.1007/s10620-022-07609-2
  2. Aguilar, F., Hussain, S. P., & Cerutti, P. (1993). Aflatoxin B1 induces the transversion of G-->T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. Proc Natl Acad Sci U S A, 90(18), 8586-8590. https://doi.org/10.1073/pnas.90.18.8586
  3. Ascha, M. S., Hanouneh, I. A., Lopez, R., Tamimi, T. A., Feldstein, A. F., & Zein, N. N. (2010). The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology, 51(6), 1972-1978. https://doi.org/10.1002/hep.23527
  4. Asselah, T., Rubbia-Brandt, L., Marcellin, P., & Negro, F. (2006). Steatosis in chronic hepatitis C: why does it really matter? Gut, 55(1), 123-130. https://doi.org/10.1136/gut.2005.069757
  5. Atkins, J. L., Pilling, L. C., Masoli, J. A. H., Kuo, C. L., Shearman, J. D., Adams, P. C., & Melzer, D. (2020). Association of Hemochromatosis HFE p.C282Y Homozygosity With Hepatic Malignancy. JAMA, 324(20), 2048-2057. https://doi.org/10.1001/jama.2020.21566
  6. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca-a Cancer Journal for Clinicians, 68(6), 394-424. https://doi.org/10.3322/caac.21492
  7. Brooks, P. J., & Theruvathu, J. A. (2005). DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis. Alcohol, 35(3), 187-193. https://doi.org/10.1016/j.alcohol.2005.03.009
  8. Butt, A. S., Hamid, S., Wadalawala, A. A., Ghufran, M., Javed, A. A., Farooq, O., Ahmed, B., Ul Haq, T., & Jafri, W. (2013). Hepatocellular carcinoma in Native South Asian Pakistani population; trends, clinico-pathological characteristics & differences in viral marker negative & viral-hepatocellular carcinoma. BMC Res Notes, 6, 137. https://doi.org/10.1186/1756-0500-6-137
  9. Calle, E. E., & Kaaks, R. (2004). Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer, 4(8), 579-591. https://doi.org/10.1038/nrc1408
  10. Chawla, A., Chawla, R., & Jaggi, S. (2016). Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian J Endocrinol Metab, 20(4), 546-551. https://doi.org/10.4103/2230-8210.183480
  11. Chen, C. L., Yang, H. I., Yang, W. S., Liu, C. J., Chen, P. J., You, S. L., Wang, L. Y., Sun, C. A., Lu, S. N., Chen, D. S., & Chen, C. J. (2008). Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology, 135(1), 111-121. https://doi.org/10.1053/j.gastro.2008.03.073
  12. Chidambaranathan-Reghupaty, S., Fisher, P. B., & Sarkar, D. (2021). Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv Cancer Res, 149, 1-61. https://doi.org/10.1016/bs.acr.2020.10.001
  13. Consultation, W. H. O. E. (2004). Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet, 363(9403), 157-163. https://doi.org/10.1016/S0140-6736(03)15268-3
  14. Davila, J. A., Morgan, R. O., Shaib, Y., McGlynn, K. A., & El-Serag, H. B. (2005). Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut, 54(4), 533-539. https://doi.org/10.1136/gut.2004.052167
  15. Donato, F., Boffetta, P., & Puoti, M. (1998). A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma. Int J Cancer, 75(3), 347-354. https://doi.org/10.1002/(sici)1097-0215(19980130)75:3 3.0.co;2-2
  16. Donato, F., Tagger, A., Gelatti, U., Parrinello, G., Boffetta, P., Albertini, A., Decarli, A., Trevisi, P., Ribero, M. L., Martelli, C., Porru, S., & Nardi, G. (2002). Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol, 155(4), 323-331. https://doi.org/10.1093/aje/155.4.323
  17. Donohue, T. M., Jr. (2007). Alcohol-induced steatosis in liver cells. World J Gastroenterol, 13(37), 4974-4978. https://doi.org/10.3748/wjg.v13.i37.4974
  18. El-Serag, H. B. (2004). Hepatocellular carcinoma: recent trends in the United States. Gastroenterology, 127(5 Suppl 1), S27-34. https://doi.org/10.1053/j.gastro.2004.09.013
  19. El-Serag, H. B., & Rudolph, K. L. (2007). Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 132(7), 2557-2576. https://doi.org/10.1053/j.gastro.2007.04.061
  20. European Association for the Study of the Liver. Electronic address, e. e. e., & European Association for the Study of the, L. (2022). EASL Clinical Practice Guidelines on haemochromatosis. J Hepatol, 77(2), 479-502. https://doi.org/10.1016/j.jhep.2022.03.033
  21. Fattovich, G., Giustina, G., Degos, F., Tremolada, F., Diodati, G., Almasio, P., Nevens, F., Solinas, A., Mura, D., Brouwer, J. T., Thomas, H., Njapoum, C., Casarin, C., Bonetti, P., Fuschi, P., Basho, J., Tocco, A., Bhalla, A., Galassini, R.,. Realdi, G. (1997). Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology, 112(2), 463-472. https://doi.org/10.1053/gast.1997.v112.pm9024300
  22. Federation, B. I. D. (2014). IDF diabetes atlas. http://www.idf.org/sites/default/files/EN_6E_Atlas_Full_0.pdf.
  23. Fujino, Y., Mizoue, T., Tokui, N., & Yoshimura, T. (2001). Prospective study of diabetes mellitus and liver cancer in Japan. Diabetes Metab Res Rev, 17(5), 374-379. https://doi.org/10.1002/dmrr.214
  24. Ganne-Carrie, N., & Nahon, P. (2019). Hepatocellular carcinoma in the setting of alcohol-related liver disease. J Hepatol, 70(2), 284-293. https://doi.org/10.1016/j.jhep.2018.10.008
  25. Garcia-Compean, D., Jaquez-Quintana, J. O., Gonzalez-Gonzalez, J. A., & Maldonado-Garza, H. (2009). Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management. World J Gastroenterol, 15(3), 280-288. https://doi.org/10.3748/wjg.15.280
  26. Hagstrom, H., Ndegwa, N., Jalmeus, M., Ekstedt, M., Posserud, I., Rorsman, F., Nyhlin, N., Klintman, D., Werner, M., Marschall, H. U., Askling, J., Stal, P., & Swedish Hepatology Study, G. (2021). Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers. Liver International, 41(3), 545-553. https://doi.org/10.1111/liv.14792
  27. Holstein, A., Hinze, S., Thiessen, E., Plaschke, A., & Egberts, E. H. (2002). Clinical implications of hepatogenous diabetes in liver cirrhosis. Journal of Gastroenterology and Hepatology, 17(6), 677-681. https://doi.org/DOI 10.1046/j.1440-1746.2002.02755.x
  28. Hui, A. M., Makuuchi, M., & Li, X. (1998). Cell cycle regulators and human hepatocarcinogenesis. Hepatogastroenterology, 45(23), 1635-1642. https://www.ncbi.nlm.nih.gov/pubmed/9840120
  29. IOTF, T. I. A. f. t. S. o. O. a. t. I. O. T. F. A. I. a. (2000). The Asia-Pacific perspective: redefining obesity and its treatment.
  30. Irshad, M., Gupta, P., & Irshad, K. (2017). Molecular basis of hepatocellular carcinoma induced by hepatitis C virus infection. World J Hepatol, 9(36), 1305-1314. https://doi.org/10.4254/wjh.v9.i36.1305
  31. Jafri, W., & Kamran, M. (2019). Hepatocellular Carcinoma in Asia: A Challenging Situation. Euroasian J Hepatogastroenterol, 9(1), 27-33. https://doi.org/10.5005/jp-journals-10018-1292
  32. Kelly, A. L., Rhodes, D. A., Roland, J. M., Schofield, P., & Cox, T. M. (1998). Hereditary juvenile haemochromatosis: a genetically heterogeneous life-threatening iron-storage disease. QJM, 91(9), 607-618. https://doi.org/10.1093/qjmed/91.9.607
  33. Kew, M. C. (2003). Synergistic interaction between aflatoxin B and hepatitis B virus in hepatocarcinogenesis. Liver International, 23(6), 405-409. https://doi.org/DOI 10.1111/j.1478-3231.2003.00869.x
  34. Kiran, Z., Zuberi, B. F., Anis, D., Qadeer, R., Hassan, K., & Afsar, S. (2013). Insulin resistance in non-diabetic patients of chronic Hepatitis C. Pak J Med Sci, 29(1), 201-204. https://doi.org/10.12669/pjms.291.2888
  35. Kumar, P., Mahato, D. K., Kamle, M., Mohanta, T. K., & Kang, S. G. (2016). Aflatoxins: A Global Concern for Food Safety, Human Health and Their Management. Front Microbiol, 7, 2170. https://doi.org/10.3389/fmicb.2016.02170
  36. Kuske, L., Mensen, A., Mullhaupt, B., Negro, F., Semela, D., Moradpour, D., Male, P. J., Heim, M. H., Malinverni, R., Cerny, A., Dufour, J. F., & Swiss Hepatitis, C. C. S. (2012). Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma. Swiss Med Wkly, 142, w13651. https://doi.org/10.4414/smw.2012.13651
  37. Lackner, C., & Tiniakos, D. (2019). Fibrosis and alcohol-related liver disease. J Hepatol, 70(2), 294-304. https://doi.org/10.1016/j.jhep.2018.12.003
  38. Liaw, Y. F., Tai, D. I., Chu, C. M., & Chen, T. J. (1988). The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology, 8(3), 493-496. https://doi.org/10.1002/hep.1840080310
  39. Lumley, S. F., McNaughton, A. L., Klenerman, P., Lythgoe, K. A., & Matthews, P. C. (2018). Hepatitis B Virus Adaptation to the CD8+ T Cell Response: Consequences for Host and Pathogen. Front Immunol, 9, 1561. https://doi.org/10.3389/fimmu.2018.01561
  40. Mani, H., & Van Thiel, D. H. (2001). Mesenchymal tumors of the liver. Clin Liver Dis, 5(1), 219-257, viii. https://doi.org/10.1016/s1089-3261(05)70162-8
  41. Maurice, J., & Manousou, P. (2018). Non-alcoholic fatty liver disease. Clin Med (Lond), 18(3), 245-250. https://doi.org/10.7861/clinmedicine.18-3-245
  42. Memon, M. S., Arain, Z. I., Naz, F., Zaki, M., Kumar, S., & Burney, A. A. (2013). Prevalence of type 2 diabetes mellitus in hepatitis C virus infected population: a Southeast Asian study. J Diabetes Res, 2013, 539361. https://doi.org/10.1155/2013/539361
  43. Muto, Y., Sato, S., Watanabe, A., Moriwaki, H., Suzuki, K., Kato, A., Kato, M., Nakamura, T., Higuchi, K., Nishiguchi, S., Kumada, H., Ohashi, Y., & Long-Term Survival Study, G. (2006). Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis. Hepatol Res, 35(3), 204-214. https://doi.org/10.1016/j.hepres.2006.04.007
  44. Ohishi, W., Fujiwara, S., Cologne, J. B., Suzuki, G., Akahoshi, M., Nishi, N., Takahashi, I., & Chayama, K. (2008). Risk factors for hepatocellular carcinoma in a Japanese population: a nested case-control study. Cancer Epidemiol Biomarkers Prev, 17(4), 846-854. https://doi.org/10.1158/1055-9965.EPI-07-2806
  45. Paganoni, R. L., A.; Vujic Spasic, M. (2021). Iron at the Interface of Hepatocellular Carcinoma. Int. J. Mol. Sci., 22,4097. https://doi.org/https://doi.org/10.3390/ijms22084097
  46. Peng, X. M., Peng, W. W., & Yao, J. L. (1998). Codon 249 mutations of p53 gene in development of hepatocellular carcinoma. World J Gastroenterol, 4(2), 125-127. https://doi.org/10.3748/wjg.v4.i2.125
  47. Pilling, L. C., Tamosauskaite, J., Jones, G., Wood, A. R., Jones, L., Kuo, C. L., Kuchel, G. A., Ferrucci, L., & Melzer, D. (2019). Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank. BMJ, 364, k5222. https://doi.org/10.1136/bmj.k5222
  48. Polesel, J., Zucchetto, A., Montella, M., Dal Maso, L., Crispo, A., La Vecchia, C., Serraino, D., Franceschi, S., & Talamini, R. (2009). The impact of obesity and diabetes mellitus on the risk of hepatocellular carcinoma. Ann Oncol, 20(2), 353-357. https://doi.org/10.1093/annonc/mdn565
  49. Sahinbegovic, E., Dallos, T., Aigner, E., Axmann, R., Manger, B., Englbrecht, M., Schoniger-Hekele, M., Karonitsch, T., Stamm, T., Farkas, M., Karger, T., Stolzel, U., Keysser, G., Datz, C., Schett, G., & Zwerina, J. (2010). Musculoskeletal disease burden of hereditary hemochromatosis. Arthritis Rheum, 62(12), 3792-3798. https://doi.org/10.1002/art.27712
  50. Sarma, U. P., Bhetaria, P. J., Devi, P., & Varma, A. (2017). Aflatoxins: Implications on Health. Indian J Clin Biochem, 32(2), 124-133. https://doi.org/10.1007/s12291-017-0649-2
  51. Saunders, D., Seidel, D., Allison, M., & Lyratzopoulos, G. (2010). Systematic review: the association between obesity and hepatocellular carcinoma - epidemiological evidence. Aliment Pharmacol Ther, 31(10), 1051-1063. https://doi.org/10.1111/j.1365-2036.2010.04271.x
  52. Schuppan, D., Ashfaq-Khan, M., Yang, A. T., & Kim, Y. O. (2018). Liver fibrosis: Direct antifibrotic agents and targeted therapies. Matrix Biol, 68-69, 435-451. https://doi.org/10.1016/j.matbio.2018.04.006
  53. Setshedi, M., Wands, J. R., & Monte, S. M. (2010). Acetaldehyde adducts in alcoholic liver disease. Oxid Med Cell Longev, 3(3), 178-185. https://doi.org/10.4161/oxim.3.3.12288
  54. Shi, J., Zhu, L., Liu, S., & Xie, W. F. (2005). A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer, 92(3), 607-612. https://doi.org/10.1038/sj.bjc.6602333
  55. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 71(3), 209-249. https://doi.org/10.3322/caac.21660
  56. Szabo, G., & Bala, S. (2010). Alcoholic liver disease and the gut-liver axis. World J Gastroenterol, 16(11), 1321-1329. https://doi.org/10.3748/wjg.v16.i11.1321
  57. Takano, S., Yokosuka, O., Imazeki, F., Tagawa, M., & Omata, M. (1995). Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients. Hepatology, 21(3), 650-655. https://www.ncbi.nlm.nih.gov/pubmed/7875662
  58. Tan, A., Koh, S., & Bertoletti, A. (2015). Immune Response in Hepatitis B Virus Infection. Cold Spring Harb Perspect Med, 5(8), a021428. https://doi.org/10.1101/cshperspect.a021428
  59. Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65(2), 87-108. https://doi.org/10.3322/caac.21262
  60. Turati, F., Galeone, C., Rota, M., Pelucchi, C., Negri, E., Bagnardi, V., Corrao, G., Boffetta, P., & La Vecchia, C. (2014). Alcohol and liver cancer: a systematic review and meta-analysis of prospective studies. Ann Oncol, 25(8), 1526-1535. https://doi.org/10.1093/annonc/mdu020
  61. Turkez, H., & Sisman, T. (2012). The genoprotective activity of resveratrol on aflatoxin B(1)-induced DNA damage in human lymphocytes in vitro. Toxicol Ind Health, 28(5), 474-480. https://doi.org/10.1177/0748233711414614
  62. Valderrama-Trevino, A. I., Barrera-Mera, B., Ceballos-Villalva, J. C., & Montalvo-Jave, E. E. (2017). Hepatic Metastasis from Colorectal Cancer. Euroasian J Hepatogastroenterol, 7(2), 166-175. https://doi.org/10.5005/jp-journals-10018-1241
  63. Vanni, E., Abate, M. L., Gentilcore, E., Hickman, I., Gambino, R., Cassader, M., Smedile, A., Ferrannini, E., Rizzetto, M., Marchesini, G., Gastaldelli, A., & Bugianesi, E. (2009). Sites and mechanisms of insulin resistance in nonobese, nondiabetic patients with chronic hepatitis C. Hepatology, 50(3), 697-706. https://doi.org/10.1002/hep.23031
  64. Yamauchi, R., Takata, K., Shinagawa, Y., Tanaka, T., Fukuda, H., Fukuda, S., Kunimoto, H., Umeda, K., Morihara, D., Yokoyama, K., Takeyama, Y., Irie, M., Shakado, S., Mizoguchi, M., Hisano, S., Yoshimitsu, K., & Sakisaka, S. (2019). Hepatocellular Carcinoma Arising in a Non-cirrhotic Liver with Secondary Hemochromatosis. Intern Med, 58(5), 661-665. https://doi.org/10.2169/internalmedicine.0973-18
  65. Younossi, Z. M. (2019). Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol, 70(3), 531-544. https://doi.org/10.1016/j.jhep.2018.10.033
  66. Zoulim, F. (2005). New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA. J Hepatol, 42(3), 302-308. https://doi.org/10.1016/j.jhep.2004.12.015
  67. Fattovich, G., Giustina, G., Degos, F., Tremolada, F., Diodati, G., Almasio, P., Nevens, F., Solinas, A., Mura, D., Brouwer, J. T., Thomas, H., Njapoum, C., Casarin, C., Bonetti, P., Fuschi, P., Basho, J., Tocco, A., Bhalla, A., Galassini, R.,. Realdi, G. (1997). Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology, 112(2), 463-472. https://doi.org/10.1053/gast.1997.v112.pm9024300
  68. Paganoni, R. L., A.; Vujic Spasic, M. (2021). Iron at the Interface of Hepatocellular Carcinoma. Int. J. Mol. Sci., 22,4097. https://doi.org/https://doi.org/10.3390/ijms22084097