Abstract
Objective: Intrahepatic cholangiocarcinoma (ICC) is a rare type of primary liver cancer (PLC) arising from intrahepatic bile ducts. We carried out a case–control study to assess the association between ICC and hepatitis B and C virus (HBV and HCV) infections, alcohol intake, and hepatolithiasis in Brescia, North Italy. Methods: Among 370 subjects with histology-based diagnosis of PLC who were resident in the area and hospitalized in 1995–2000, 26 (7%) ICC cases were identified. A total of 824 subjects unaffected by hepatic diseases and frequency-matched with PLC cases by age, sex, date, and hospital of admission were recruited as controls. Results: Among ICC cases the mean age was 65 years, 80.8% were males, and 38.5% had cirrhosis. Seropositivity for anti-HCV, HBsAg, alcohol intake > 80 g/day and history of hepatolithiasis were found in 25%, 13%, 23.1%, and 26.9% of ICC cases and in 5.8%, 6.7%, 32.9%, and 10.6% of controls, respectively. The odds ratios adjusted for demographic factors by logistic regression (95% confidence interval; 95% CI) were 9.7 (1.6–58.9) for anti-HCV, 2.7 (0.4–18.4) for HBsAg, and 6.7 (1.3–33.4) for hepatolithiasis, whereas no association was found with alcohol drinking. Conclusions: HCV and hepatolithiasis may be risk factors for ICC in Western countries.
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De Groen PC, Gores GJ, LaRusso NF, Gundrson LL, Nagorney DM (1999) Biliary tract cancers. N Engl J Med 341: 1368-1378.
Parkin DM, Oshima H, Srivatanakul P, Vatanasapt V (1993) Cholangiocarcinoma: epidemiology, mechanism of carcinogenesis and prevention. Cancer Epidemiol Biomarkers Prev 2: 537-544.
Chalasani N, Baluyut A, Ismail A et al. (2000) Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study. Hepatology 31: 7-11.
Kornfeld D, Ekbom A, Ihre T (1997) Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. Scand J Gastroenterol 32: 1042-1045.
Broomè U, Olsson R, Lööf L, et al. (1996) Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut 38: 610-615.
Farrant JM, Hayllar KM, Wilkinson ML, et al. (1991) Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology 100: 1710-1717.
Farges O, Malassagne B, Sebagh M, Bismuth H (1995) Primary sclerosing cholangitis: liver transplantation or biliary surgery. Surgery 117: 146-155.
Schrumpf E, Abdelnoor M, Fausa O, Elgjo K, Jenssen E, Kolmannskog F (1994) Risk factors in primary sclerosing cholangitis. J Hepatol 21: 1061-1066.
Kubo S, Kinoshita H, Hirohashi K, Hamba H (1995) Hepatolithiasis associated with cholangiocarcinoma. World J Surg 19: 637-641.
Su CH, Shyr YM, Lui WY, P'Eng FK (1997) Hepatolithiasis associated with cholangiocarcinoma. Br J Surg 84: 969-975.
Chen MF, Jan YY, Wang CS, et al. (1993) A reappraisal of cholangiocarcinoma in patients with hepatolithiasis. Cancer 71: 2461-2465.
Chen MF, Jan YY, Jeng LB, et al. (1999) Intrahepatic cholangiocarcinoma in Taiwan. J Hepatobiliary Pancreat Surg 6: 136-141.
Kaczynski J, Hansson G, Wallerstedt S (1998) Incidence, etiologic aspects and clinicopathologic features in intrahepatic cholangiocellular carcinoma. Acta Oncol 37: 77-83.
Koga A, Ichimiya H, Yamaguchi K, Miyazaki K, Nakayama F (1985) Hepatolithiasis associated with cholangiocarcinoma. Cancer 55: 2826-2829.
Chijiiwa K, Ichimiya H, Kuroki S, Koga A, Nakayama F (1993) Late development of cholangiocarcinoma after the treatment of hepatolithiasis. Surg Gynecol Obstet 177: 279-282.
Okuda K, Kubo Y, Okazaki N, et al. (1977) Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma. Cancer 39: 232-246.
International Agency for Research on Cancer (1988) Alcohol Drinking. IARC Monographs on the evaluation of carcinogenic risks to humans. Lyon: IARC.
International Agency for Research on Cancer (1994) Hepatitis viruses. IARC Monographs on the evaluation of carcinogenic risks to humans. Lyon: IARC.
Altaee MY, Johnson PJ, Farrant JM, Williams R (1991) Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma. Cancer 68: 2051-2055.
Hardell L, Bengtsson NO, Jonsson U, Eriksson S, Larsson LG (1984) Aetiological aspects on primary liver cancer with special regard to alcohol, organic solvents and acute intermittent porphyria: an epidemiological investigation. Br J Cancer 50: 389-397.
Parkin DM, Srivatanakul P, Khlat M, et al. (1991) Liver cancer in Thailand. I. A case-control study of cholangiocarcinoma. Int J Cancer 48: 323-328.
Tomimatsu M, Ishiguro N, Taniai M, et al. (1993) Hepatitis C virus antibody in patients with primary liver cancer (hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma) in Japan. Cancer 72: 683-688.
Yamamoto M, Takasaki K, Nakano M, Saito A (1998) Minute nodular intrahepatic cholangiocarcinoma. Cancer 82: 2145-2149.
Songsivilai S, Dharakul T, Kanistanon D (1996) Hepatitis C virus genotypes in patients with hepatocellular carcinoma and cholangiocarcinoma in Thailand. Trans R Soc Trop Med Hyg 90: 505-507.
Kobayashi M, Ikeda K, Saitoh S, et al. (2000) Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis. Cancer 88: 2471-2477.
Sorensen HT, Friis S, Olsen JH, et al. (1998) Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark. Hepatology 28: 921-925.
Shin H, Lee C, Park H, et al. (1996) Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case control study in Pusan, Korea. Int J Epidemiol 25: 933-940.
Donato F, Tagger A, Chiesa R, et al. (1997) Hepatitis B and C virus infection, alcohol drinking and hepatocellular carcinoma: a case-control study in Italy. Hepatology 26: 579-584.
Tagger A, Donato F, Ribero ML, et al. (1999) Case-control study on hepatitis C virus as a risk factor for hepatocellular carcinoma: the role of HCV genotypes and the synergism with hepatitis B virus and alcohol. Int J Cancer 81: 695-699.
Corrao G, Busellu G, Valenti M, et al. (1994) Reproducibility of measuring lifetime alcohol consumption by a simple interviewadministered questionnaire. Alcologia 6: 127-135.
Rothman KJ (1986) Modern Epidemiology. Boston, MA: Little, Brown & Co.
Chiesa R, Donato F, Tomasoni S, Portolani N, Favret M, Nardi G (1995) Primary liver cancer in a high-incidence area in North Italy: etiological hypothesis arising from routinely collected data. Eur J Epidemiol 11: 435-442.
Zanetti R, Crosignani P, Rosso S (1997) Cancer in Italy — Incidence Data from Cancer Registries, vol. 2: 1988–1992. Torino: Il Pensiero Scientifico Editore, p. 85.
Liver Cancer Study Group of Japan (1990) Primary liver cancer in Japan. Clinicopathological features and results of surgical treatment. Ann Surg 211: 277-287.
Broomè U, Löfberg R, Veress B, Eriksson LS (1995) Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology 22: 1404-1408.
Okolicsanyi L, Fabris L, Viaggi S, Carulli N, Podda M, Ricci G (1996) Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicenter study. Eur J Gastroenterol Hepatol 8: 685-691.
Attili AF, Carulli N, Roda E, et al. (1995) Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study Group on Cholclithiasis (M.I.COL.) Am J Epidemiol 141: 158-165.
Holzinger F, Z'graggen K, Büchler MW (1999) Mechanism of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma. Ann Oncol 10(Suppl. 4): S122-S126.
Nakanuma Y, Terada T, Tanaka Y, Ohta G (1985) Are hepatolithiasis and cholangiocarcinoma aetiologically related? Virchows Arch A Pathol Anat Histopathol 406: 45-58.
Bergquist A, Glaumann H, Persson B, Broomè U (1998) Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study. Hepatology 27: 311-316.
Munoz N, Bosch X (1990) Epidemiology of hepatocellular carcinoma. In: Okuda K, Ishak KG, eds. Neoplasms of the Liver. Tokyo: Springer Verlag, pp. 3-19.
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Donato, F., Gelatti, U., Tagger, A. et al. Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case–control study in Italy. Cancer Causes Control 12, 959–964 (2001). https://doi.org/10.1023/A:1013747228572
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DOI: https://doi.org/10.1023/A:1013747228572