{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:07:00Z","timestamp":1793387220453,"version":"4.5.0"},"reference-count":43,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2003,11,27]],"date-time":"2003-11-27T00:00:00Z","timestamp":1069891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:p>\n                    <jats:bold>Abstract:<\/jats:bold>\n                    Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B\n                    <jats:sub>1<\/jats:sub>\n                    (AFB\n                    <jats:sub>1<\/jats:sub>\n                    ), two of the major risk factors in the multifactorial aetiology of hepatocellular carcinoma (HCC), co\u2010exist in those countries with the highest incidences of and the youngest patients with this tumour, raising the possibility of a synergistic carcinogenic interaction between the two agents. Experimental studies in HBV\u2010transgenic mice and woodchucks infected with woodchuck hepatitis virus were the first to show a synergistic hepatocarcinogenic effect between hepadnaviral infection and AFB\n                    <jats:sub>1<\/jats:sub>\n                    exposure. With the availability of urinary and serum biomarkers that more accurately reflect dietary exposure to AFB\n                    <jats:sub>1<\/jats:sub>\n                    than did the initially used food sampling and dietary questionnaires, cohort studies of patients with HCC in China and Taiwan have provided compelling evidence for a multiplicative or sub\u2010multiplicative interaction between HBV and AFB\n                    <jats:sub>1<\/jats:sub>\n                    in the genesis of human HCC. A number of possible mechanisms for the interaction have been suggested. Chronic HBV infection may induce the cytochrome P450s that metabolise inactive AFB\n                    <jats:sub>1<\/jats:sub>\n                    to the mutagenic AFB\n                    <jats:sub>1<\/jats:sub>\n                    \u20108,9\u2010epoxide. Hepatocyte necrosis and regeneration and the generation of oxygen and nitrogen reactive species resulting from chronic HBV infection increase the likelihood of the AFB\n                    <jats:sub>1<\/jats:sub>\n                    \u2010induced p53 249\n                    <jats:sup>ser<\/jats:sup>\n                    and other mutations and the subsequent clonal expansion of cells containing these mutations. Nuclear excision repair, which is normally responsible for removing AFB\n                    <jats:sub>1<\/jats:sub>\n                    \u2013DNA adducts, is inhibited by HBV\u00d7protein, favouring the persistence of existing mutations. This protein also increases the overall frequency of DNA mutations, including the p53 249\n                    <jats:sup>ser<\/jats:sup>\n                    mutation, and may contribute to uncontrolled cell cycling when p53 is non\u2010functional.\n                  <\/jats:p>","DOI":"10.1111\/j.1478-3231.2003.00869.x","type":"journal-article","created":{"date-parts":[[2003,11,27]],"date-time":"2003-11-27T11:15:33Z","timestamp":1069931733000},"page":"405-409","source":"Crossref","is-referenced-by-count":245,"title":["Synergistic interaction between aflatoxin B\n                    <sub>1<\/sub>\n                    and hepatitis B virus in hepatocarcinogenesis"],"prefix":"10.1111","volume":"23","author":[{"given":"Michael C.","family":"Kew","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,11,27]]},"reference":[{"key":"e_1_2_4_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910390502"},{"key":"e_1_2_4_3_2","first-page":"2506","article-title":"Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China","volume":"49","author":"Yeh F\u2010S","year":"1989","journal-title":"Cancer Res"},{"key":"e_1_2_4_4_2","first-page":"1278","article-title":"Synergy between hepatitis B virus expression and chemical hepatocarcinogenesis in transgenic mice","volume":"51","author":"Sell S","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_4_5_2","first-page":"3318","article-title":"Synergistic hepatocarcinogenic effect of hepadnaviral infection and dietary aflatoxin B1 in woodchucks","volume":"55","author":"Bannasch P","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/10.6.1099"},{"key":"e_1_2_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19971114)73:4<587::AID-IJC21>3.0.CO;2-5"},{"key":"e_1_2_4_8_2","first-page":"599","volume-title":"Viral Hepatitis and Liver Disease","author":"Tennant B C","year":"1990"},{"key":"e_1_2_4_9_2","first-page":"45","volume-title":"IARC Monographs on the Evaluation of Carcinogenic Risks to Humans","author":"IARC","year":"1994"},{"key":"e_1_2_4_10_2","first-page":"2156","article-title":"Contribution of aflatoxin B1 and duck hepatitis B virus in the induction of liver tumors in ducks","volume":"50","author":"Cova L","year":"1990","journal-title":"Cancer Res"},{"key":"e_1_2_4_11_2","first-page":"3","article-title":"A follow\u2010up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People's Republic of China","volume":"3","author":"Qian G S","year":"1994","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91528-G"},{"key":"e_1_2_4_13_2","first-page":"620","article-title":"Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan","volume":"67","author":"Wang L\u2010Y","year":"1996","journal-title":"Br J Cancer"},{"key":"e_1_2_4_14_2","first-page":"3471","article-title":"Mutations, chronic hepatitis B virus infection, and aflatoxin exposure in hepatocellular carcinoma in Taiwan","volume":"57","author":"Lunn R M","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300204"},{"key":"e_1_2_4_16_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.36366"},{"key":"e_1_2_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(97)80178-X"},{"key":"e_1_2_4_18_2","first-page":"1289","article-title":"Genetic polymorphisms of glutathione\u2010S\u2010transferases M1 and T1 associated with susceptibility to aflatoxin\u2010related carcinogenesis among chronic hepatitis B carriers","volume":"22","author":"Sun C\u2010A","year":"2001","journal-title":"a nested case\u2013control study in Taiwan"},{"key":"e_1_2_4_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840160508"},{"key":"e_1_2_4_20_2","first-page":"128","article-title":"Chronic hepatitis B carriers with null genotypes glutathione\u2010S\u2010transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma","volume":"59","author":"Chen C\u2010J","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.6.2384"},{"key":"e_1_2_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/350427a0"},{"key":"e_1_2_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/350429a0"},{"key":"e_1_2_4_24_2","first-page":"260","article-title":"A p53 mutational hotspot in primary liver cancer is geographically localised to high aflatoxin areas of the world","volume":"338","author":"Ozturk M","year":"1991","journal-title":"Lancet"},{"key":"e_1_2_4_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.34.040194.001031"},{"key":"e_1_2_4_26_2","first-page":"6098","article-title":"Mutations of p53 in hepatocellular carcinomas in Taiwan","volume":"52","author":"Sheu J\u2010C","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_4_27_2","first-page":"617","article-title":"Hepatitis B, aflatoxin B1, and p53 codon 249 mutation in hepatocellular carcinoma from Guangxi, People's Republic of China, and a meta\u2010analysis of existing studies","volume":"10","author":"Stern M C","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_4_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.1999.tb00015.x"},{"key":"e_1_2_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(92)90253-9"},{"key":"e_1_2_4_30_2","first-page":"1223","article-title":"Association of aflatoxin B1\u2010albumin adduct levels with hepatitis B surface antigen status among adolescents in Taiwan","volume":"10","author":"Chen S\u2010Y","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_4_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.2000.00664.x"},{"key":"e_1_2_4_32_2","first-page":"221","article-title":"Molecular dosimetry of aflatoxin\u2010N7 \u2013guanine in human urine obtained in The Gambia","volume":"1","author":"Groopman J D","year":"1992","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_4_33_2","first-page":"253","article-title":"Temporal patterns of aflatoxin\u2010albumin adducts in hepatitis B surface antigen\u2010positive and\u2010negative residents of Daxin, Qidong County, People's Republic of China","volume":"5","author":"Wang J S","year":"1996","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_4_34_2","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC382_6"},{"key":"e_1_2_4_35_2","first-page":"966","article-title":"Determinants of formation of aflatoxin\u2010albumin adducts","volume":"87","author":"Sun C\u2010A","year":"2002","journal-title":"a seven township study in Taiwan"},{"key":"e_1_2_4_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.2940110204"},{"key":"e_1_2_4_37_2","first-page":"555","article-title":"Aflatoxin, liver enzymes and hepatitis B virus infection in Gambian children","volume":"2","author":"Wild C P","year":"1993","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90770-8"},{"key":"e_1_2_4_39_2","first-page":"2875","article-title":"Woodchuck hepatitis virus surface antigen induces nitric oxide synthesis in hepatocytes","volume":"15","author":"Liu R H","year":"1994","journal-title":"possible role in hepatocarcinogenesis"},{"key":"e_1_2_4_40_2","first-page":"253","article-title":"Chronic infection and inflammatory processes as cancer risk factors","volume":"305","author":"Ishima H","year":"1994","journal-title":"possible role for nitric oxide in carcinogenesis"},{"key":"e_1_2_4_41_2","first-page":"2277","article-title":"Oxy\u2010radical induced mutagenesis of hotspot codons 248 and 249 of the human p53 gene","volume":"9","author":"Hussain S P","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_4_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990315)80:6<875::AID-IJC13>3.0.CO;2-Z"},{"key":"e_1_2_4_43_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-11-2765"},{"key":"e_1_2_4_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.22.11770-11774.2002"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1478-3231.2003.00869.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1478-3231.2003.00869.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T10:35:53Z","timestamp":1697193353000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1478-3231.2003.00869.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,27]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,12]]}},"alternative-id":["10.1111\/j.1478-3231.2003.00869.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1478-3231.2003.00869.x","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,11,27]]}}}