Epidemiology of primary and secondary liver cancers.

Primary liver cancer is the sixth most common cancer worldwide with a wide geographic distribution. The incidence of primary liver cancer is increasing and there is still a higher prevalence in developing countries. Early recognition remains an obstacle and lack of it results in poor outcomes for hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, and cholangiocarcinoma. The most common risk factors associated with HCC are hepatitis B and chronic hepatitis C infections, alcohol use, smoking, and aflatoxin exposure. Emerging risk factors such as obesity might play an important role in the future because of the increasing prevalence of this condition.

[1]  I. Purchase,et al.  Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei. , 1985, British Journal of Cancer.

[2]  N. Mcintyre,et al.  Hepatocellular Carcinoma Arising in Non-Cirrhotic Haemochromatosis , 1995, HPB surgery : a world journal of hepatic, pancreatic and biliary surgery.

[3]  Hai-rim Shin,et al.  Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea. , 1996, International journal of epidemiology.

[4]  P. Giral,et al.  Survival, liver failure, and hepatocellular carcinoma in obesity‐related cryptogenic cirrhosis , 2002, Hepatology.

[5]  A. Kuijsten,et al.  Population-Attributable Risk of Dietary Aflatoxins and Hepatitis B Virus Infection with Respect to Hepatocellular Carcinoma , 2004, Nutrition and cancer.

[6]  H. Tsukuma,et al.  Case‐Control Study of Hepatocellular Carcinoma among Koreans Living in Osaka, Japan , 1994, Japanese journal of cancer research : Gann.

[7]  S. Franceschi,et al.  N‐Acetyltransferase‐2, glutathione S‐transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: A case‐control study , 2005, International journal of cancer.

[8]  Hou Pao-Chang The relationship between primary carcinoma of the liver and infestation with Clonorchis sinensis. , 1956 .

[9]  R. Hultcrantz,et al.  Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. , 2003, Gastroenterology.

[10]  S. Lee,et al.  Turnover of biliary epithelial cells in Clonorchis sinensis infected rats. , 1993, The Korean journal of parasitology.

[11]  K. Ishak,et al.  HEPATIC ANGIOSARCOMA ASSOCIATED WITH ANDROGENIC-ANABOLIC STEROIDS , 1979, The Lancet.

[12]  Shou-Dong Lee,et al.  Are alcohol, tobacco and obesity genuine risk factors for hepatocellular carcinoma? , 2005, Journal of hepatology.

[13]  D. Parkin,et al.  Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention. , 1993, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[14]  M. Kew Synergistic interaction between aflatoxin B1 and hepatitis B virus in hepatocarcinogenesis , 2003, Liver international : official journal of the International Association for the Study of the Liver.

[15]  H. Whittle,et al.  Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West Africa. , 2004, Pharmacogenetics.

[16]  S. Hosoda,et al.  Survey of thorotrast-associated liver cancers in Japan. , 1983, Journal of the National Cancer Institute.

[17]  Chun-Ying Wu,et al.  What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma? , 2002, Journal of gastroenterology and hepatology.

[18]  M. Thun,et al.  Tobacco smoke and involuntary smoking. , 2004, IARC monographs on the evaluation of carcinogenic risks to humans.

[19]  Xiao Wang,et al.  A case-control study of risk factors for hepatocellular carcinoma in Henan, China. , 1998, The American journal of tropical medicine and hygiene.

[20]  C. Hellerbrand,et al.  HFE C282Y heterozygosity in hepatocellular carcinoma: evidence for an increased prevalence. , 2003, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[21]  F. Farinati,et al.  Hepatocellular carcinoma, alcohol, and cirrhosis: Facts and hypotheses , 1991, Digestive Diseases and Sciences.

[22]  M. Tsutsumi,et al.  Relative risk for the development of hepatocellular carcinoma in alcoholic patients with cirrhosis: a multiple logistic-regression coefficient analysis. , 1996, Alcoholism, clinical and experimental research.

[23]  W. Su,et al.  A clinical study of 130 patients with biliary tract cancers and periampullary tumors. , 1996, Oncology.

[24]  Chien-Jen Chen,et al.  Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan. , 2003, American journal of epidemiology.

[25]  R. A. Metcalf,et al.  Mutational hot spot in the p53 gene in human hepatocellular carcinomas , 1991, Nature.

[26]  A. Pezzoli,et al.  Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis. , 1996, Journal of hepatology.

[27]  A. Bergquist,et al.  Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: A case‐control study , 1998, Hepatology.

[28]  V. Wiwanitkit,et al.  The prevalence of hepatitis B seropositivity among patients with cholangiocarcinoma. , 2002, Viral immunology.

[29]  Yuan‐Jen Wang,et al.  Clinical experience in 126 patients with tissue‐proved proximal cholangiocarcinoma , 1994, Journal of gastroenterology and hepatology.

[30]  P. Pineau,et al.  Hepatocellular carcinoma occurring in nonfibrotic liver: Epidemiologic and histopathologic analysis of 80 French cases , 2000, Hepatology.

[31]  C. Avellini,et al.  Carriage of HFE mutations and outcome of surgical resection for hepatocellular carcinoma in cirrhotic patients , 2000, Cancer.

[32]  A. Athanasiadou,et al.  The leading role of hepatitis B and C viruses as risk factors for the development of hepatocellular carcinoma. A case control study. , 1995, Journal of clinical gastroenterology.

[33]  Josepa Ribes,et al.  Primary liver cancer: worldwide incidence and trends. , 2004, Gastroenterology.

[34]  C. Zhang,et al.  Case-control study of cigarette smoking and primary hepatoma in an aflatoxin-endemic region of China: a protective effect. , 1991, Pharmacogenetics.

[35]  I Mangelsdorf,et al.  Vinyl chloride: still a cause for concern. , 2000, Environmental health perspectives.

[36]  S. Porru,et al.  Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. , 2002, American journal of epidemiology.

[37]  A. Oshima,et al.  Follow‐up study of hbs ag‐positive blood donors with special reference to effect of drinking and smoking on development of liver cancer , 1984, International journal of cancer.

[38]  J. Crawford,et al.  Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis. , 1988, Gastroenterology.

[39]  K. Boberg,et al.  Cholangiocarcinoma in Primary Sclerosing Cholangitis: Risk Factors and Clinical Presentation , 2002, Scandinavian journal of gastroenterology.

[40]  E. Molina,et al.  Clinical Manifestations of Primary Hepatic Angiosarcoma , 2003, Digestive Diseases and Sciences.

[41]  S. Thung,et al.  Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients. , 2000, Chinese medical journal.

[42]  S. Caldwell,et al.  Obesity and hepatocellular carcinoma. , 2004, Gastroenterology.

[43]  C. Silver,et al.  Incidence and Sites of Distant Metastases from Head and Neck Cancer , 2001, ORL.

[44]  H. El‐Serag Hepatocellular carcinoma: an epidemiologic view. , 2002, Journal of clinical gastroenterology.

[45]  S. Horie,et al.  c‐erbB‐2 protein is expressed in hepatolithiasis and cholangiocarcinoma , 1998, Histopathology.

[46]  X. Wang,et al.  Molecular pathogenesis of human hepatocellular carcinoma. , 2002, Toxicology.

[47]  T. Hsiao,et al.  Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk , 2000, Gut.

[48]  W. Tsai,et al.  Polycyclic aromatic hydrocarbon‐DNA adducts in liver tissues of hepatocellular carcinoma patients and controls , 2002, International journal of cancer.

[49]  K. McGlynn,et al.  Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study. , 2005, Gastroenterology.

[50]  W. London,et al.  Eight-year follow-up of the 90,000-person Haimen City cohort: I. Hepatocellular carcinoma mortality, risk factors, and gender differences. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[51]  A. Wald,et al.  Hepatic angiosarcoma associated with short-term arsenic ingestion. , 1982, The American journal of medicine.

[52]  Eugene R. Schiff,et al.  Treatment of Chronic Hepatitis C with Recombinant Interferon Alfa , 1989 .

[53]  Schwartz Da Cholangiocarcinoma associated with liver fluke infection: a preventable source of morbidity in Asian immigrants. , 1986 .

[54]  C. la Vecchia,et al.  Risk factors for hepatocellular carcinoma in Northern Italy , 1988, International journal of cancer.

[55]  N. Day,et al.  Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma , 1987, International journal of cancer.

[56]  M. Gail,et al.  Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1 , 1999, Hepatology.

[57]  King-Teh Lee,et al.  Expression of Transforming Growth Factor Betas and Their Signaling Receptors in Stone-containing Intrahepatic Bile Ducts and Cholangiocarcinoma , 2003, World Journal of Surgery.

[58]  C. J. Chen,et al.  Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. , 1997, American journal of epidemiology.

[59]  G. Bunin Nongenetic causes of childhood cancers: evidence from international variation, time trends, and risk factor studies. , 2004, Toxicology and applied pharmacology.

[60]  J. Crowe,et al.  Hepatocellular carcinoma arising in the absence of cirrhosis in genetic haemochromatosis: three case reports and review of literature. , 1999, European journal of gastroenterology & hepatology.

[61]  Masao Tanaka,et al.  Cholangiocellular carcinoma depending on the kind of intrahepatic calculi in patients with hepatolithiasis. , 2002, Hepato-gastroenterology.

[62]  S. Pauker,et al.  Cost-effectiveness of Interferon-2b Treatment for Hepatitis B e Antigen-Positive Chronic Hepatitis B , 1995, Annals of Internal Medicine.

[63]  S. Chiplunkar,et al.  The detection of HBV antigens and HBx-transcripts in an Indian fibrolamellar carcinoma patient: a case study. , 2002, Liver.

[64]  K. Ishak,et al.  Epidemiology of hepatic angiosarcoma in the United States: 1964-1974. , 1981, Environmental health perspectives.

[65]  M. Haswell-Elkins,et al.  Cross‐sectional study of Opisthorchis viverrini infection and cholangiocarcinoma in communities within a high‐risk area in northeast thailand , 1994, International journal of cancer.

[66]  B. Macmahon,et al.  Smoking and hepatitis B-negative primary hepatocellular carcinoma. , 1980, Journal of the National Cancer Institute.

[67]  A. Luciani,et al.  Carcinome hépatocellulaire en l’absence de cirrhose au cours d’une stéato-hépatite non alcoolique , 2004 .

[68]  J. Feusner,et al.  Hepatoblastoma and low birth weight: a trend or chance observation? , 2002, Medical and pediatric oncology.

[69]  M. Nakagawa,et al.  Diabetes Mellitus May Be Associated with Hepatocarcinogenesis in Patients with Chronic Hepatitis C , 2002, Digestive Diseases and Sciences.

[70]  J. Esteban,et al.  Long interval between HCV infection and development of hepatocellular carcinoma. , 2008, Liver.

[71]  A. Muñoz,et al.  Temporal patterns of aflatoxin-albumin adducts in hepatitis B surface antigen-positive and antigen-negative residents of Daxin, Qidong County, People's Republic of China. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[72]  William M. Lee,et al.  Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. , 1998, The New England journal of medicine.

[73]  K. Lillemoe,et al.  Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. , 1996, Annals of surgery.

[74]  C. la Vecchia,et al.  Attributable risks for hepatocellular carcinoma in northern Italy. , 1997, European journal of cancer.

[75]  K. Chayama,et al.  Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus–related cirrhosis , 2000, Cancer.

[76]  R O Morgan,et al.  Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study , 2005, Gut.

[77]  P. Boffetta,et al.  Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: A case‐control study in Italy , 1997 .

[78]  C. Pairojkul,et al.  Association of antibodies to Opisthorchis viverrini with hepatobiliary disease in northeastern Thailand. , 1994, The American journal of tropical medicine and hygiene.

[79]  B. Werner,et al.  Association of hepatitis b virus infection with hepatocellular carcinoma in american patients , 1980, International journal of cancer.

[80]  A. Lonardo,et al.  The wide spectrum of steatohepatitis: a report of four cases and a review of the literature , 2004, European journal of gastroenterology & hepatology.

[81]  Jian-Min Yuan,et al.  Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. , 2004, Cancer.

[82]  H. El‐Serag,et al.  The role of diabetes in hepatocellular carcinoma: a case-control study among United States veterans , 2001, American Journal of Gastroenterology.

[83]  R. Chapman Risk factors for biliary tract carcinogenesis. , 1999, Annals of oncology : official journal of the European Society for Medical Oncology.

[84]  L. Abenhaim,et al.  Viral infections and chemical exposures as risk factors for hepatocellular carcinoma in Vietnam , 1993, International journal of cancer.

[85]  A. Ferraris,et al.  Mutations of the HFE gene and the risk of hepatocellular carcinoma. , 1999, Blood cells, molecules & diseases.

[86]  Y. Ko,et al.  Survival and distribution pattern of childhood liver cancer in Taiwan. , 1998, European journal of cancer.

[87]  S. Osada,et al.  Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation , 2001, Journal of Gastroenterology.

[88]  J. Reitsma,et al.  Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population , 2002, Gut.

[89]  M. Hara,et al.  Prospective study of hepatitis B and C viral infections, cigarette smoking, alcohol consumption, and other factors associated with hepatocellular carcinoma risk in Japan. , 2000, American journal of epidemiology.

[90]  H. Adami,et al.  Excess risk of primary liver cancer in patients with diabetes mellitus. , 1996, Journal of the National Cancer Institute.

[91]  L. Covolo,et al.  Etiology of hepatocellular carcinoma influences clinical and pathologic features but not patient survival. , 2003 .

[92]  J. Goedert,et al.  Ser-249 p53 Mutations in Plasma DNA of Patients With Hepatocellular Carcinoma From The Gambia. , 2000, Journal of the National Cancer Institute.

[93]  S. Chevret,et al.  Hepatocellular carcinoma without cirrhosis in the West: epidemiological factors and histopathology of the non-tumorous liver. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. , 1999, Journal of hepatology.

[94]  J. Marrero,et al.  NAFLD may be a common underlying liver disease in patients with hepatocellular Carcinoma in the United States , 2002, Hepatology.

[95]  A. Oshima,et al.  A case‐control study of hepatocellular carcinoma in osaka, Japan , 1990, International journal of cancer.

[96]  Kenneth Koury,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[97]  B. Henderson,et al.  Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. , 1989, Cancer research.

[98]  Y. Hiraku,et al.  Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in macrophage RAW cell line. , 2005, International journal for parasitology.

[99]  S. Sherlock,et al.  Viruses and hepatocellular carcinoma. , 1994, Gut.

[100]  K. Ishak,et al.  Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[101]  B. Choi,et al.  Clonorchiasis and Cholangiocarcinoma: Etiologic Relationship and Imaging Diagnosis , 2004, Clinical Microbiology Reviews.

[102]  J. Hoofnagle,et al.  NIH conference. Hepatocellular carcinoma. , 1988, Annals of internal medicine.

[103]  H. Sriplung,et al.  Histologic subtypes of hepatocellular carcinoma in the southern Thai population. , 2003, Asian Pacific journal of cancer prevention : APJCP.

[104]  K. Boberg,et al.  Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations and Tp53 dysfunction are implicated in the neoplastic development. , 2000, Journal of hepatology.

[105]  H. Adami,et al.  Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma , 2000, International journal of cancer.

[106]  N. Chalasani,et al.  Cholangiocarcinoma in patients with primary sclerosing cholangitis: A multicenter case‐control study , 2000, Hepatology.

[107]  S. Saab,et al.  Fibrolamellar hepatocellular carcinoma , 1996, Digestive Diseases and Sciences.

[108]  Teruaki Kimura,et al.  Hepatocellular carcinoma with nonalcoholic steatohepatitis , 2004, Journal of Gastroenterology.

[109]  H. Pitt,et al.  Choledochal Cyst Disease A Changing Pattern of Presentation , 1994, Annals of surgery.

[110]  K. Ishak,et al.  Arsenic-related hepatic angiosarcoma. , 1981, American journal of industrial medicine.

[111]  T. Dharakul,et al.  Hepatitis C virus genotypes in patients with hepatocellular carcinoma and cholangiocarcinoma in Thailand. , 1996, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[112]  Chien-Jen Chen,et al.  Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan , 1996, International journal of cancer.

[113]  V. Čulić,et al.  Liver angiosarcoma and hemangiopericytoma after occupational exposure to vinyl chloride monomer. , 2000, Environmental health perspectives.

[114]  H. Hsu,et al.  Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls. , 2000, JAMA.

[115]  H. Adami,et al.  Role of diabetes mellitus in the etiology of hepatocellular carcinoma. , 2000, Journal of the National Cancer Institute.

[116]  P. Pisani,et al.  Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand , 2004, Tropical medicine & international health : TM & IH.

[117]  T. Hwang,et al.  A reappraisal of cholangiocarcinoma in patient with hepatolithiasis , 1993, Cancer.

[118]  F. X. Bosch,et al.  Risk factors for hepatocellular carcinoma in catalonia, spain , 1990, International journal of cancer.

[119]  M. Taniai,et al.  Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH , 2004, Journal of Gastroenterology.

[120]  R. Semba,et al.  Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis. , 2004, Nitric oxide : biology and chemistry.

[121]  O. Farges,et al.  Intrahepatic cholangiocarcinoma and hepatolithiasis: an unusual association in Western countries. , 2002, European journal of gastroenterology & hepatology.

[122]  M. Cappellini,et al.  Iron in the pathogenesis of hepatocellular carcinoma. , 1991, The Italian journal of gastroenterology.

[123]  E. Schiff,et al.  Lamivudine as initial treatment for chronic hepatitis B in the United States. , 1999, The New England journal of medicine.

[124]  S. Hirohashi,et al.  Multistage carcinogenesis of liver-fluke-associated cholangiocarcinoma in Thailand. , 1991, Princess Takamatsu symposia.

[125]  P. Toghill,et al.  Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis. , 1988, Gut.

[126]  A. Ekbom,et al.  Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis. A population-based study. , 1997, Scandinavian journal of gastroenterology.

[127]  K. Hasegawa,et al.  Comparison of hepatocellular carcinoma patients with alcoholic liver disease and nonalcoholic steatohepatitis. , 2004, Alcoholism, clinical and experimental research.

[128]  P. Johnson,et al.  Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma , 1991, Cancer.

[129]  D. V. van Thiel,et al.  Mesenchymal tumors of the liver. , 2001, Clinics in liver disease.

[130]  D. Gouma,et al.  Choledochal cysts: age of presentation, symptoms, and late complications related to Todani's classification. , 2002, Journal of pediatric surgery.

[131]  L. Rodrigo,et al.  HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma. , 2002 .

[132]  O. Yokosuka,et al.  Incidence of hepatocellular carcinoma in chronic hepatitis B and C: A prospective study of 251 patients , 1995, Hepatology.

[133]  K. Tolman,et al.  Narrative Review: Hepatobiliary Disease in Type 2 Diabetes Mellitus , 2004, Annals of Internal Medicine.

[134]  K. Yamazaki,et al.  Lipid-rich clear-cell hepatocellular carcinoma arising in non-alcoholic steatohepatitis in a patient with diabetes mellitus. , 2001, Journal of submicroscopic cytology and pathology.

[135]  E. Schiff,et al.  A preliminary trial of lamivudine for chronic hepatitis B infection. , 1995, The New England journal of medicine.

[136]  H. Margolis,et al.  The past incidence of hepatitis C virus infection: Implications for the future burden of chronic liver disease in the United States , 2000, Hepatology.

[137]  K. Lindor,et al.  Incidence and Risk Factors for Cholangiocarcinoma in Primary Sclerosing Cholangitis , 2004, American Journal of Gastroenterology.

[138]  J. Crespo,et al.  Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma , 2005, Obesity surgery.

[139]  N. Leung,et al.  A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. , 1998, The New England journal of medicine.

[140]  M. Mattioli,et al.  Mutations in the HFE gene and their interaction with exogenous risk factors in hepatocellular carcinoma. , 2001, Blood cells, molecules & diseases.

[141]  G. Anagnostopoulos,et al.  Is hepatocellular carcinoma part of the natural history of nonalcoholic steatohepatitis? , 2003, Journal of clinical gastroenterology.

[142]  J. Fraumeni,et al.  International trends and patterns of primary liver cancer , 2001, International journal of cancer.

[143]  S. Banks,et al.  Recombinant interferon alfa therapy for chronic hepatitis C. A randomized, double-blind, placebo-controlled trial. , 1989, The New England journal of medicine.

[144]  J. Ferlay,et al.  Global Cancer Statistics, 2002 , 2005, CA: a cancer journal for clinicians.

[145]  S. Kubo,et al.  Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma , 2004, Cancer Science.

[146]  M. Mattioli,et al.  Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non–iron‐related chronic liver disease , 2001, Hepatology.

[147]  V. P. Chacko,et al.  Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition? , 2001, Cancer research.

[148]  Manal M. Hassan,et al.  Rising Prevalence of Hepatitis C Virus Infection Among Patients Recently Diagnosed With Hepatocellular Carcinoma in the United States , 2002, Journal of Clinical Gastroenterology.

[149]  R. Colombari,et al.  Hepatoblastoma in adult age: a report of two cases. , 1996, Hepato-gastroenterology.

[150]  H. Tsukuma,et al.  Risk factors for hepatocellular carcinoma among patients with chronic liver disease. , 1993, The New England journal of medicine.

[151]  M. Feitelson Hepatitis B virus in hepatocarcinogenesis , 1999, Journal of cellular physiology.

[152]  A. Buda,et al.  Increased Risk of Hepatocellular Carcinoma and Liver Cirrhosis in Vinyl Chloride Workers: Synergistic Effect of Occupational Exposure with Alcohol Intake , 2004, Environmental health perspectives.

[153]  D. Lobo,et al.  Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma. , 2004, Journal of hepatology.

[154]  K. Boberg,et al.  Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis , 2002, Gut.

[155]  K. Chayama,et al.  Interferon decreases hepatocellular carcinogenesis in patients with cirrhosis caused by the hepatitis B virus , 1998, Cancer.

[156]  H. El‐Serag,et al.  Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population‐based study , 2004, Hepatology.

[157]  H. Ikeda,et al.  Association between hepatoblastoma and very low birth weight: a trend or a chance? , 1997, The Journal of pediatrics.

[158]  J. Samet,et al.  Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. , 2004, Journal of the National Cancer Institute.

[159]  J. Ludwig,et al.  Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. , 2002, Journal of hepatology.

[160]  S. Fan,et al.  Immediate and long-term outcomes of hepatectomy for hepatolithiasis. , 2004, Surgery.

[161]  W. Stauffer,et al.  Biliary liver flukes (Opisthorchiasis and Clonorchiasis) in immigrants in the United States: often subtle and diagnosed years after arrival. , 2004, Journal of travel medicine.

[162]  J. Groopman Do aflatoxin-DNA adduct measurements in humans provide accurate data for cancer risk assessment? , 1988, IARC scientific publications.

[163]  M. Manns,et al.  Target gene modulation in hepatocellular carcinomas by decreased DNA‐binding of p53 mutations , 1997, Hepatology.

[164]  N. Ganne-Carrié,et al.  Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis , 2003, Gut.

[165]  M. Alter,et al.  Epidemiology of Hepatitis C , 2018, Clinical liver disease.

[166]  F. Callea,et al.  Intrahepatic cholangiocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case–control study in Italy , 2001, Cancer Causes & Control.

[167]  G. Loss,et al.  Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis? , 2002, Hepatology.

[168]  B. Henderson,et al.  Hepatitis B virus and cigarette smoking: risk factors for hepatocellular carcinoma in Hong Kong. , 1982, Cancer research.

[169]  C. J. Chen,et al.  A case‐control study of primary hepatocellular carcinoma in Taiwan , 1988, Cancer.

[170]  J. Mclaughlin,et al.  Hepatic Angiosarcoma Occurring After Cyclophosphamide Therapy: Case Report and Review of the Literature , 2000, American journal of clinical oncology.

[171]  P. Brissot,et al.  Primary liver cancer in genetic hemochromatosis: a clinical, pathological, and pathogenetic study of 54 cases. , 1993, Gastroenterology.

[172]  N. Kelekis,et al.  Advanced intrahepatic cholangiocarcinoma in hepatitis C virus-related decompensated cirrhosis: case report and review of the literature. , 2003, European journal of gastroenterology & hepatology.

[173]  A. Bergquist,et al.  Hepatic and extrahepatic malignancies in primary sclerosing cholangitis. , 2002, Journal of hepatology.

[174]  Lu-Yu Hwang,et al.  Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus , 2002, Hepatology.

[175]  Y. Deugnier,et al.  Iron and hepatocellular carcinoma , 2001, Journal of gastroenterology and hepatology.

[176]  C. Oon Long-term survival following treatment of hepatocellular carcinoma in Singapore: evaluation of Wellferon in the prophylaxis of high-risk pre-cancerous conditions , 2004, Cancer Chemotherapy and Pharmacology.

[177]  A. Suriawinata,et al.  Liver Pathology in Obesity , 2004, Seminars in liver disease.

[178]  Keitaro Tanaka,et al.  Hepatitis B Virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: A Case‐Control study in Fukuoka, Japan , 1992, International journal of cancer.

[179]  T. Nakashima,et al.  Pathomorphologic characteristics of 102 cases of thorotrast‐related hepatocellular carcinoma, cholangiocarcinoma, and hepatic angiosarcoma , 1988, Cancer.

[180]  Akihiro Matsumoto,et al.  Hepatocellular carcinoma: recent trends in Japan. , 2004, Gastroenterology.

[181]  Yoshiyuki Suzuki,et al.  Significance of hepatitis B virus DNA clearance and early prediction of hepatocellular carcinogenesis in patients with cirrhosis undergoing interferon therapy: Long‐term follow up of a pilot study , 2005, Journal of gastroenterology and hepatology.

[182]  V. Siskind,et al.  Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases. , 1985, Journal of the National Cancer Institute.

[183]  K. Hess,et al.  Unknown primary tumors metastatic to liver. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[184]  K. Kowdley,et al.  Hereditary hemochromatosis and cancer risk: more fuel to the fire? , 2001, Gastroenterology.

[185]  C. Chen,et al.  Elevated aflatoxin exposure and increased risk of hepatocellular carcinoma , 1996, Hepatology.

[186]  Å. Danielsson,et al.  Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. , 1996, Gut.

[187]  Z. Younossi,et al.  Obesity and Non-Alcoholic Fatty Liver Disease in Chronic Hepatitis C , 2004, Journal of clinical gastroenterology.

[188]  H. El‐Serag,et al.  Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. , 2004, Gastroenterology.

[189]  D. Chan,et al.  Hepatitis B and hepatitis C in emergency department patients. , 1992, The New England journal of medicine.

[190]  J. Hoofnagle,et al.  The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. , 1991, The American journal of gastroenterology.

[191]  R. Tamimi,et al.  Risk factors for cholangiocarcinoma in a low risk Caucasian population , 2005, Sozial- und Präventivmedizin.

[192]  E. Abdalla,et al.  Obesity and diabetes as a risk factor for hepatocellular carcinoma , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[193]  D. Parkin,et al.  Liver cancer in Thailand. I. A case‐control study of cholangiocarcinoma , 1991, International journal of cancer.

[194]  J. Olsen,et al.  Cancer risk following primary hemochromatosis: A population‐based cohort study in Denmark , 1995, International journal of cancer.

[195]  Y. Ishikawa,et al.  Microsatellite instability in thorotrast‐induced human intrahepatic cholangiocarcinoma , 2002, International journal of cancer.

[196]  K. Tsuneyama,et al.  Hepatocellular carcinoma arising in non‐alcoholic steatohepatitis , 2001, Pathology international.

[197]  C. Datz,et al.  Mutations of the HFE gene in patients with hepatocellular carcinoma. , 2003 .

[198]  Chien-Jen Chen,et al.  Urinary aflatoxin levels, hepatitis‐b virus infection and hepatocellular carcinoma in taiwan , 1993, International journal of cancer.

[199]  M. Matsuo Association between diabetes mellitus and hepatocellular carcinoma: results of a hospital- and community-based case-control study. , 2003, The Kurume medical journal.

[200]  B. Henderson,et al.  Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma , 1992, The Lancet.

[201]  A. Tóth,et al.  Prognosis of untreated liver metastasis from rectal cancer. , 1997, Acta chirurgica Hungarica.

[202]  F. Callea,et al.  Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[203]  D. Williams,et al.  Occupationally related angiosarcoma of the liver in the United Kingdom 1972-1994. , 1996, Gut.

[204]  S. Bloor,et al.  Successful treatment with adefovir dipivoxil in a patient with fibrosing cholestatic hepatitis and lamivudine resistant hepatitis B virus , 2001, Gut.

[205]  G. Royle,et al.  Breast Liver Metastases – Incidence, Diagnosis and Outcome , 1991, Journal of the Royal Society of Medicine.

[206]  N. Tanaka,et al.  The role of previous hepatitis B virus infection and heavy smoking in hepatitis C virus-related hepatocellular carcinoma. , 1996, The American journal of gastroenterology.

[207]  G. Sharp The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data. , 2002, Journal of radiation research.

[208]  J. Marrero,et al.  Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. , 2005, Journal of hepatology.

[209]  M. Sherman,et al.  Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection , 2001, Hepatology.

[210]  B. Henderson,et al.  Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the non-Asians of Los Angeles County, California. , 1991, Journal of the National Cancer Institute.

[211]  K. Sugimachi,et al.  The importance of hepatic resection for hepatocellular carcinoma originating from nonfibrotic liver. , 2000, Journal of the American College of Surgeons.

[212]  J. Gray,et al.  Diabetes mellitus and primary hepatocellular carcinoma. , 1986, The Quarterly journal of medicine.