Challenging Role of Dietary Aflatoxin B1 Exposure and Hepatitis B Infection on Risk of Hepatocellular Carcinoma


  • Basak Kucukcakan Ss.Cyril and Methodius University, Veterinary Faculty, Food Safety Department
  • Zehra Hayrulai-Musliu Ss. Cyril and Methodius University of Skopje, Faculty of Veterinary Medicine, Department of Food Safety, Skopje



Aflatoxin B1, Hepatitis B, Hepatocellular Carcinoma, Biomarker


Aflatoxins (AFT) are poisonous substances which are classified in Group 1 carcinogenic agents to humans by International Agency for Research on Cancer (IARC). AFT can occur naturally in food commodities (maize, corn, rice) as a result of fungal contamination in hot and humid environments. In the food, toxin contamination can remain during manufacturing and long after fungi have stopped being biologically active. Aflatoxin B1 (AFB1) is the most dominant and potent agent from all AFT. In developing countries, high exposure to AFB1 can cause chronic toxicity and usually increases the incidence of Hepatocellular Carcinoma (HCC). However, in these regions hepatitis B is the most common risk factor for HCC cases. Many researches were aimed to enlighten the mechanism and the role of two etiological agents on risk of HCC, but the obtained data was conflicting with each other. It was uncertain that the indicators/biomarkers might be the contribution of the carcinogenic status of the patient; and, the biomarker samples from the subject may only reflect the recent effects of the toxin exposure after consumption of AFB1 contaminated commodities. The studies were facing with the errors of methods which were un-fit to enlighten the possible interaction between Hepatitis B and AFB1 on contribution to HCC. It was pivotal to understand the effect of each risk factor in order to prevent and improve public health in poor and undeveloped regions. Although some of the studies evaluate AFB1 alone as a considerable factor on HCC risk, according to this review it was concluded vice versa. This study was aimed to clarify the main etiological agent of HCC where AFB1 and HBV are endangering public health. In additionally, the purpose was to enlighten the possible synergistic effect between these two factors among HCC pathogenesis. Hence forth, appropriate and right applications could be conducted in undeveloped countries in order to protect public health.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block

Author Biography

Basak Kucukcakan, Ss.Cyril and Methodius University, Veterinary Faculty, Food Safety Department

Ss. Cyril and Methodius University, Veterinary Faculty, Food Safety Department


Liu Y, Wu F. Global burden of aflatoxin-induced Hepatocellular Carcinoma: A risk assessment, Environ Health Persp. 2010:110:6.

Franco E, Bagnato B, et al. Hepatitis B: Epidemiology and prevention in developing countries. World J Hepatol. 2012; 4(3): 74-80.

Previsani N, Lavanchy D. Hepatitis B. World Health Organization: 2002;1-21. Accessed : August 12,2014.

Soini Y, Chia SC, Bennett WP, Groopman JD, Wang JS, DeBenedetti MG, et al. An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico. Carcinogenesis. 996:17:5:1007-12.

Bbosa SG, Kitya D, Lubega A, Okeng-Ogwal J, Anokbonggo W, Kyegombe D. Review of the biological and health effects of aflatoxins on body organs and body systems. InTech: Aflatoxins-Recent Advances and Future Prospects. 2013: 240-64.

Vandel JP, Perdew GH, Mattes BW eds. Cellular and Molecular Toxicology, Comprehensive toxicology, Amsterdam, Netherlands, 2002:14:259-61.

Kew CM. Synergistic interaction between aflatoxin B1 and hepatitis B virus in hepatocarcinogenesis, Intech: Aflatoxins - Recent Advances and Future Prospects, 2013:223-31.

Baumgartner E, Lindblade K, Gieseker K, Rogers H, et al. Case–control study of an acute aflatoxicosis outbreak, Kenya, 2004. Environ Health Persp. 2005; 113(12): 1779–1783.

Turner PC, Mendy M, Whittle H, Fortuin M, Hall AJ. Wild CP. Hepatitis B infection and aflatoxin biomarker levels in Gambian children. Trop Med Int Health. 2000; 5(12): 837–41.

Igetei R, Otegbayo AJ, et al. Detection of p53 Codon 249 mutation in Nigerian patients with hepatocellular carcinoma using a novel evaluation of cell-free DNA. Ann Hepatol. 2008:7(4): 339-344.

The forty-ninth meeting of the Joint FAO/WHO Expert, Committee on Food Additives (JECFA ), Safety Evalution of Certain Food additives and Contaminants: Who Food Additives Series 40, World Health Organization, Geneva, 1998.

Wild CP, Turner PC. The toxicology of aflatoxins as a basis for public health decisions. Mutagenesis. 2002;17:6:471–81.

Kirk GD, Lesi OA, Mendy M, Szymañska K, Whittle H, Goedert JJ, Hainaut P, Montesano R. 249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma. Oncogene. 2005;24(38):5858-67.

Stern M, Umbach M, Yu MC, et al. Hepatitis B, Aflatoxin B1, and p53 codon 249 mutation in of China, and a meta-analysis of existing studies hepatocellular carcinomas from Guangxi, People's Republic. Cancer Epidem Biomar. 2001;10:617-25.

Peers FG, Linsell CA. Dietary aflatoxins and liver cancer–A population based study in Kenya. Br J Cancer. 1973; 27: 473.

Rensburg SJ, Cook-Mozaffari P, Van Schalkwyk DJ, Van Der Watt JJ, Vincent TJ, Purchase IF. Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei. Br J Cancer. 1985; 51: 713-26.

Campbell CT, Chen J, Liu C, et al. Nonassociation of Aflatoxin with primary liver cancer in a cross-sectional ecological survey in the people's Republic of China. Cancer Res. 1990;50:6882-93.

Xu L, Qian G, Tang L, Su J, Wang J. Genetic variations of hepatitis B virus and serum aflatoxin-lysine adduct on high risk of hepatocellular carcinoma in Southern Guangxi, China, European Association For The Study of The Liver. J Hepatol. 2010; 53(4):671-6.

Srivatanakul P, Parkin M, Khlat M, Chenvidhna D, et al. Liver Cancer in Thailan. II A Case-Control Study of Heptaocellular Carcinoma. Int J Cancer. 1991; 48, 329-332.

Qian G, Ross KR, Yu M, et al. A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People’s Republic of China. Cancer Epidem Biomar. 1994;3: 3-10.

Groopman JD, Jiaqi Z, Donahue P, et al. Molecular dosimetry of urinary aflatoxin-DNA adducts in people living in Guangxi Autonomous region, People's Republic of China. Cancer Res. 1992;52: 45-52.

Wu HC, Wang Q, Yang HI, Ahsan H, Tsai WY, Wang LY, Chen SY, Chen CJ, Santella RM. Aflatoxin B1 exposure, hepatitis B virus infection, and hepatocellular carcinoma in Taiwan. Cancer Epidemiol Biomar. 2009;18(3):846-53.

Ronald K, Wogan G, et al. Urinary aflatoxin biomarkers and risk of Hepatocellular Carcinoma. The Lancet. 1992; 339: 8799: 943.

Groopman JD, Wild C, et al. Molecular epidemiology of aflatoxin exposures: Validation of aflatoxin-N7-guanine levels in urine as a biomarker in experimental rat models and humans. Environ Health Persp. 1993; 99: 107-113.

Fujimoto Y, Hampton L, Luo L, et al. Low frequency of p53 gene mutation in tumors Induced by Aflatoxin B 1 in nonhuman primates. Cancer Res. 1992; 52:1044-46.

Wu C, Santella R. The role of aflatoxins in Hepatocellular Carcinoma. Hepat Mon. 2012;12: e72384.

Kew CM. Aflatoxins as a cause of Hepatocellular Carcinoma. J Gastrointestin Liver Dis. 2013; 22: 3: 305-10.

Lereau M, Gouas D, et al. Interactions between hepatitis B virus and aflatoxin B1: effects on p53 induction in HepaRG cells. Journal of Gen Virol. 2012; 93: 640–650.

Bennet JW, Klinch M. Mycotoxins. Clin Microbiol Rev. 2003; 16(3):497–516.

Mangussen A, Parsi M. Aflatoxins, hepatocellular carcinoma and public health. World J Gastroenterol. 2013;14: 19(10): 1508-12.

Autrup H, Seremet T, Wakhisi J, Wasunna A. Aflatoxin exposure measured by urinary excretion of aflatoxin B1-guanine adduct and hepatitis B virus infection in areas with different liver cancer incidence in Kenya. Cancer Res. 1987;47(13):3430-3.



How to Cite

Kucukcakan B, Hayrulai-Musliu Z. Challenging Role of Dietary Aflatoxin B1 Exposure and Hepatitis B Infection on Risk of Hepatocellular Carcinoma. Open Access Maced J Med Sci [Internet]. 2015 Mar. 25 [cited 2022 Aug. 15];3(2):363-9. Available from:



F - Review Articles