HEMOCHROMATOSIS AND HEPATOCELLULAR CARCINOMA

Öz

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.

Anahtar Kelimeler

• Hemochromatosis
• Hepatocellular carcinoma
• HFE gene
• Iron
• Iron overload

Kaynakça

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<347::aid-ijc4>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