Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case–control study in Italy Article DOI:
10.1023/A:1013747228572 Cite this article as: Donato, F., Gelatti, U., Tagger, A. et al. Cancer Causes Control (2001) 12: 959. doi:10.1023/A:1013747228572 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. hepatitis B virus hepatitis C virus hepatolithiasis intrahepatic cholangiocarcinoma References
De Groen PC, Gores GJ, LaRusso NF, Gundrson LL, Nagorney DM (1999) Biliary tract cancers.
N Engl J Med
Parkin DM, Oshima H, Srivatanakul P, Vatanasapt V (1993) Cholangiocarcinoma: epidemiology, mechanism of carcinogenesis and prevention.
Cancer Epidemiol Biomarkers Prev
Chalasani N, Baluyut A, Ismail A
(2000) Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study.
Kornfeld D, Ekbom A, Ihre T (1997) Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis.
Scand J Gastroenterol
Broomè U, Olsson R, Lööf L,
(1996) Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.
Farrant JM, Hayllar KM, Wilkinson ML,
(1991) Natural history and prognostic variables in primary sclerosing cholangitis.
Farges O, Malassagne B, Sebagh M, Bismuth H (1995) Primary sclerosing cholangitis: liver transplantation or biliary surgery.
Schrumpf E, Abdelnoor M, Fausa O, Elgjo K, Jenssen E, Kolmannskog F (1994) Risk factors in primary sclerosing cholangitis.
Kubo S, Kinoshita H, Hirohashi K, Hamba H (1995) Hepatolithiasis associated with cholangiocarcinoma.
World J Surg
Su CH, Shyr YM, Lui WY, P'Eng FK (1997) Hepatolithiasis associated with cholangiocarcinoma.
Br J Surg
Chen MF, Jan YY, Wang CS,
(1993) A reappraisal of cholangiocarcinoma in patients with hepatolithiasis.
Chen MF, Jan YY, Jeng LB,
(1999) Intrahepatic cholangiocarcinoma in Taiwan.
J Hepatobiliary Pancreat Surg
Kaczynski J, Hansson G, Wallerstedt S (1998) Incidence, etiologic aspects and clinicopathologic features in intrahepatic cholangiocellular carcinoma.
Koga A, Ichimiya H, Yamaguchi K, Miyazaki K, Nakayama F (1985) Hepatolithiasis associated with cholangiocarcinoma.
Chijiiwa K, Ichimiya H, Kuroki S, Koga A, Nakayama F (1993) Late development of cholangiocarcinoma after the treatment of hepatolithiasis.
Surg Gynecol Obstet
Okuda K, Kubo Y, Okazaki N,
(1977) Clinical aspects of intrahepatic bile duct carcinoma including hilar carcinoma.
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.
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
Parkin DM, Srivatanakul P, Khlat M,
(1991) Liver cancer in Thailand. I. A case-control study of cholangiocarcinoma.
Int J Cancer
Tomimatsu M, Ishiguro N, Taniai M,
(1993) Hepatitis C virus antibody in patients with primary liver cancer (hepatocellular carcinoma, cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma) in Japan. Cancer
Yamamoto M, Takasaki K, Nakano M, Saito A (1998) Minute nodular intrahepatic cholangiocarcinoma.
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
Kobayashi M, Ikeda K, Saitoh S,
(2000) Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis.
Sorensen HT, Friis S, Olsen JH,
(1998) Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark.
Shin H, Lee C, Park H,
(1996) Hepatitis B and C virus,
for the risk of liver cancer: a case control study in Pusan, Korea.
Int J Epidemiol
Donato F, Tagger A, Chiesa R,
(1997) Hepatitis B and C virus infection, alcohol drinking and hepatocellular carcinoma: a case-control study in Italy.
Tagger A, Donato F, Ribero ML,
(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
Corrao G, Busellu G, Valenti M,
(1994) Reproducibility of measuring lifetime alcohol consumption by a simple interviewadministered questionnaire.
Rothman KJ (1986)
. 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
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.
Broomè U, Löfberg R, Veress B, Eriksson LS (1995) Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential.
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
Attili AF, Carulli N, Roda E,
(1995) Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study Group on Cholclithiasis (M.I.COL.)
Am J Epidemiol
Holzinger F, Z'graggen K, Büchler MW (1999) Mechanism of biliary carcinogenesis: a pathogenetic multi-stage cascade towards cholangiocarcinoma.
(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
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.
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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