Epidemiology of Primary and Secondary Liver Cancers

ABSTRACT

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.

KEYWORDS

Primary liver cancer - hepatocellular carcinoma - cholangiocarcinoma - chronic hepatitis B - chronic hepatitis C

REFERENCES

• 1 El-Serag H B. Hepatocellular carcinoma: an epidemiologic view.  J Clin Gastroenterol. 2002;  35 S72-S78
• 2 Lenhard R, Osteen RT, Gansler T Clinical Oncology. Atlanta, GA; Blackwell Publishing, Inc 2001
• 3 Parkin D M, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002.  CA Cancer J Clin. 2005;  55 74-108
• 4 McGlynn K A, Tsao L, Hsing A W, Devesa S S, Fraumeni Jr J F. International trends and patterns of primary liver cancer.  Int J Cancer. 2001;  94 290-296
• 5 Kew M C. Hepatic tumors and cysts. In: Feldman M, Friedman LS, Sleisenger MH, Scharschmidt BF Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. Philadelphia; Saunders 2002: 1583-1588
• 6 Fong Y, Kemeny N, Lawrence T S. Cancer of the liver and biliary tree. In: Devita VT, Hellman S, Rosenberg SA Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia; Lippincott Williams and Wilkins 2001: 1162-1187
• 7 Kiyosawa K, Umemura T, Ichijo T et al.. Hepatocellular carcinoma: recent trends in Japan.  Gastroenterology. 2004;  127 S17-S26
• 8 Bosch F X, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends.  Gastroenterology. 2004;  127 S5-S16
• 9 Ries LAG, Eisner MP, Kosary CL, et al SEER Cancer Statistics Review, 1975-2002. Bethesda, MD; National Cancer Institute 2005 Available at: http://seer.cancer.gov/csr/1975_2002
• 10 Surveillance, Epidemiology, and End Results (SEER) Program .http://Available at: www.seer.cancer.gov SEER*Stat Databases. Incidence-SEER 13 Regs Public-Use, Nov 2004 Sub for Expanded Races (1992-2002) and Incidence-SEER 13 Regs excluding AK Public-Use, Nov 2004 Sub for Hispanics (1992-2002), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch released April 2005, based on the November 2004 submission. 
• 11 Di Bisceglie A M, Order S E, Klein J L et al.. The role of chronic viral hepatitis in hepatocellular carcinoma in the United States.  Am J Gastroenterol. 1991;  86 335-338
• 12 Hassan M M, Frome A, Patt Y Z, El-Serag H B. Rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States.  J Clin Gastroenterol. 2002;  35 266-269
• 13 Godley P A, Sandler R S. Liver cancer. In: Everhart JE Digestive Diseases in United States: Epidemiology and Impact. Washington, DC; Government Printing Office 1994: 227-241
• 14 Kew M C. Hepatic tumors and cysts. In: Feldman M, Friedman LS, Sleisenger MH, Scharschmidt BF Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. Philadelphia; Saunders 2002: 1577-1602
• 15 Takano S, Yokosuka O, Imazeki F, Tagawa M, Omata M. Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients.  Hepatology. 1995;  21 650-655
• 16 Castells L, Vargas V, Gonzalez A, Esteban J, Esteban R, Guardia J. Long interval between HCV infection and development of hepatocellular carcinoma.  Liver. 1995;  15 159-163
• 17 Sherlock S. Viruses and hepatocellular carcinoma.  Gut. 1994;  35 828-832
• 18 Yarrish R L, Werner B G, Blumberg B S. Association of hepatitis B virus infection with hepatocellular carcinoma in American patients.  Int J Cancer. 1980;  26 711-715
• 19 Alter M J. Epidemiology of hepatitis C.  Hepatology. 1997;  26 62S-65S
• 20 Kelen G D, Green G B, Purcell R H et al.. Hepatitis B and hepatitis C in emergency department patients.  N Engl J Med. 1992;  326 1399-1404
• 21 McQuillan G M, Alter M J, Everhart J E. Viral hepatitis. In: Everhart JE Digestive Diseases in the United States: Epidemiology and Impact. Washington, DC; Government Printing Office 1994: 127-156
• 22 Centers for Disease Control and Prevention (CDC) . Incidence of acute hepatitis B: United States, 1990-2002.  MMWR Morb Mortal Wkly Rep. 2004;  52 1252-1254
• 23 Feitelson M A. Hepatitis B virus in hepatocarcinogenesis.  J Cell Physiol. 1999;  181 188-202
• 24 Shimada M, Rikimaru T, Sugimachi K et al.. The importance of hepatic resection for hepatocellular carcinoma originating from nonfibrotic liver.  J Am Coll Surg. 2000;  191 531-537
• 25 Di Bisceglie A M, Rustgi V K, Hoofnagle J H, Dusheiko G M, Lotze M T. NIH conference: hepatocellular carcinoma.  Ann Intern Med. 1988;  108 390-401
• 26 Chang M H, Shau W Y, Chen C J et al.. Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls.  JAMA. 2000;  284 3040-3042
• 27 Armstrong G L, Alter M J, McQuillan G M, Margolis H S. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States.  Hepatology. 2000;  31 777-782
• 28 Davis G L, Balart L A, Schiff E R et al.. Treatment of chronic hepatitis C with recombinant interferon alfa: a multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group.  N Engl J Med. 1989;  321 1501-1506
• 29 Di Bisceglie A M, Martin P, Kassianides C et al.. Recombinant interferon alfa therapy for chronic hepatitis C: a randomized, double-blind, placebo-controlled trial.  N Engl J Med. 1989;  321 1506-1510
• 30 Manns M P, McHutchison J G, Gordon S C et al.. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.  Lancet. 2001;  358 958-965
• 31 McHutchison J G, Gordon S C, Schiff E R et al.. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group.  N Engl J Med. 1998;  339 1485-1492
• 32 Ikeda K, Kobayashi M, Saitoh S 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.  J Gastroenterol Hepatol. 2005;  20 95-102
• 33 Ikeda K, Saitoh S, Suzuki Y et al.. Interferon decreases hepatocellular carcinogenesis in patients with cirrhosis caused by the hepatitis B virus: a pilot study.  Cancer. 1998;  82 827-835
• 34 Mazzella G, Accogli E, Sottili S et al.. Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis.  J Hepatol. 1996;  24 141-147
• 35 Oon C J. Long-term survival following treatment of hepatocellular carcinoma in Singapore: evaluation of Wellferon in the prophylaxis of high-risk pre-cancerous conditions.  Cancer Chemother Pharmacol. 1992;  31(suppl) S137-S142
• 36 Wong J B, Koff R S, Tine F, Pauker S G. Cost-effectiveness of interferon-alpha 2b treatment for hepatitis B e antigen-positive chronic hepatitis B.  Ann Intern Med. 1995;  122 664-675
• 37 Dienstag J L, Perrillo R P, Schiff E R, Bartholomew M, Vicary C, Rubin M. A preliminary trial of lamivudine for chronic hepatitis B infection.  N Engl J Med. 1995;  333 1657-1661
• 38 Dienstag J L, Schiff E R, Wright T L et al.. Lamivudine as initial treatment for chronic hepatitis B in the United States.  N Engl J Med. 1999;  341 1256-1263
• 39 Lai C L, Chien R N, Leung N W et al.. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.  N Engl J Med. 1998;  339 61-68
• 40 Walsh K M, Woodall T, Lamy P, Wight D G, Bloor S, Alexander G J. Successful treatment with adefovir dipivoxil in a patient with fibrosing cholestatic hepatitis and lamivudine resistant hepatitis B virus.  Gut. 2001;  49 436-440
• 41 de Man R A, Wolters L M, Nevens F et al.. Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection.  Hepatology. 2001;  34 578-582
• 42 Hassan M M, Hwang L Y, Hatten C J et al.. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus.  Hepatology. 2002;  36 1206-1213
• 43 Jee S H, Ohrr H, Sull J W, Samet J M. Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea.  J Natl Cancer Inst. 2004;  96 1851-1856
• 44 La Vecchia C, Negri E, Decarli A, D'Avanzo B, Franceschi S. Risk factors for hepatocellular carcinoma in northern Italy.  Int J Cancer. 1988;  42 872-876
• 45 Marrero J A, Fontana R J, Fu S, Conjeevaram H S, Su G L, Lok A S. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma.  J Hepatol. 2005;  42 218-224
• 46 Mayans M V, Calvet X, Bruix J et al.. Risk factors for hepatocellular carcinoma in Catalonia, Spain.  Int J Cancer. 1990;  46 378-381
• 47 Sun C A, Wu D M, Lin C C et al.. Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: a prospective study of 12,008 men in Taiwan.  Am J Epidemiol. 2003;  157 674-682
• 48 Yu M C, Tong M J, Govindarajan S, Henderson B E. Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the non-Asians of Los Angeles County, California.  J Natl Cancer Inst. 1991;  83 1820-1826
• 49 Yuan J M, Govindarajan S, Arakawa K, Yu M C. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the US.  Cancer. 2004;  101 1009-1017
• 50 Braga C, La Vecchia C, Negri E, Franceschi S. Attributable risks for hepatocellular carcinoma in northern Italy.  Eur J Cancer. 1997;  33 629-634
• 51 Donato F, Tagger A, Chiesa R et al.. Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study.  Hepatology. 1997;  26 579-584
• 52 Tsutsumi M, Ishizaki M, Takada A. Relative risk for the development of hepatocellular carcinoma in alcoholic patients with cirrhosis: a multiple logistic-regression coefficient analysis.  Alcohol Clin Exp Res. 1996;  20 758-762
• 53 Tsukuma H, Hiyama T, Oshima A et al.. A case-control study of hepatocellular carcinoma in Osaka, Japan.  Int J Cancer. 1990;  45 231-236
• 54 Donato F, Tagger A, Gelatti U et al.. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women.  Am J Epidemiol. 2002;  155 323-331
• 55 Tanaka K, Hirohata T, Takeshita S et al.. Hepatitis B virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: a case-control study in Fukuoka, Japan.  Int J Cancer. 1992;  51 509-514
• 56 Evans A A, Chen G, Ross E A, Shen F M, Lin W Y, London W T. Eight-year follow-up of the 90,000-person Haimen City cohort. I: hepatocellular carcinoma mortality, risk factors, and gender differences.  Cancer Epidemiol Biomarkers Prev. 2002;  11 369-376
• 57 Zhang J Y, Wang X, Han S G, Zhuang H. A case-control study of risk factors for hepatocellular carcinoma in Henan, China.  Am J Trop Med Hyg. 1998;  59 947-951
• 58 Goritsas C P, Athanasiadou A, Arvaniti A, Lampropoulou-Karatza C. The leading role of hepatitis B and C viruses as risk factors for the development of hepatocellular carcinoma: a case control study.  J Clin Gastroenterol. 1995;  20 220-224
• 59 Naccarato R, Farinati F. Hepatocellular carcinoma, alcohol, and cirrhosis: facts and hypotheses.  Dig Dis Sci. 1991;  36 1137-1142
• 60 Bralet M P, Regimbeau J M, Pineau P et al.. Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases.  Hepatology. 2000;  32 200-204
• 61 Chiesa R, Donato F, Tagger A et al.. Etiology of hepatocellular carcinoma in Italian patients with and without cirrhosis.  Cancer Epidemiol Biomarkers Prev. 2000;  9 213-216
• 62 Grando-Lemaire V, Guettier C, Chevret S, Beaugrand M, Trinchet J C. Hepatocellular carcinoma without cirrhosis in the West: epidemiological factors and histopathology of the non-tumorous liver. Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire.  J Hepatol. 1999;  31 508-513
• 63 Cordier S, Le T B, Verger P et al.. Viral infections and chemical exposures as risk factors for hepatocellular carcinoma in Vietnam.  Int J Cancer. 1993;  55 196-201
• 64 Yu M W, Hsu F C, Sheen I S et al.. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers.  Am J Epidemiol. 1997;  145 1039-1047
• 65 Kuper H, Tzonou A, Kaklamani E et al.. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma.  Int J Cancer. 2000;  85 498-502
• 66 Mastrangelo G, Fedeli U, Fadda E et al.. Increased risk of hepatocellular carcinoma and liver cirrhosis in vinyl chloride workers: synergistic effect of occupational exposure with alcohol intake.  Environ Health Perspect. 2004;  112 1188-1192
• 67 Bradbear R A, Bain C, Siskind V et al.. Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases.  J Natl Cancer Inst. 1985;  75 81-84
• 68 Hsing A W, McLaughlin J K, Olsen J H, Mellemkjar L, Wacholder S, Fraumeni Jr J F. Cancer risk following primary hemochromatosis: a population-based cohort study in Denmark.  Int J Cancer. 1995;  60 160-162
• 69 Davila J A, Morgan R O, Shaib Y, McGlynn K A, El-Serag H B. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study.  Gut. 2005;  54 533-539
• 70 El-Serag H B, Richardson P A, Everhart J E. The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans.  Am J Gastroenterol. 2001;  96 2462-2467
• 71 Cauza E, Peck-Radosavljevic M, Ulrich-Pur H et al.. Mutations of the HFE gene in patients with hepatocellular carcinoma.  Am J Gastroenterol. 2003;  98 442-447
• 72 Elmberg M, Hultcrantz R, Ekbom A et al.. Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives.  Gastroenterology. 2003;  125 1733-1741
• 73 Gelatti U, Donato F, Tagger A et al.. Etiology of hepatocellular carcinoma influences clinical and pathologic features but not patient survival.  Am J Gastroenterol. 2003;  98 907-914
• 74 Fracanzani A L, Conte D, Fraquelli M 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.  Hepatology. 2001;  33 647-651
• 75 Blumberg R S, Chopra S, Ibrahim R et al.. Primary hepatocellular carcinoma in idiopathic hemochromatosis after reversal of cirrhosis.  Gastroenterology. 1988;  95 1399-1402
• 76 Deugnier Y M, Guyader D, Crantock L et al.. Primary liver cancer in genetic hemochromatosis: a clinical, pathological, and pathogenetic study of 54 cases.  Gastroenterology. 1993;  104 228-234
• 77 Goh J, Callagy G, McEntee G, O'Keane J C, Bomford A, Crowe J. Hepatocellular carcinoma arising in the absence of cirrhosis in genetic haemochromatosis: three case reports and review of literature.  Eur J Gastroenterol Hepatol. 1999;  11 915-919
• 78 Thompson N P, Stansby G, Jarmulowicz M, Hobbs K E, McIntyre N. Hepatocellular carcinoma arising in non-cirrhotic haemochromatosis.  HPB Surg. 1995;  8 163-166
• 79 Fellows I W, Stewart M, Jeffcoate W J, Smith P G, Toghill P J. Hepatocellular carcinoma in primary haemochromatosis in the absence of cirrhosis.  Gut. 1988;  29 1603-1606
• 80 Boige V, Castera L, de Roux N et al.. Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis.  Gut. 2003;  52 1178-1181
• 81 Racchi O, Mangerini R, Rapezzi D et al.. Mutations of the HFE gene and the risk of hepatocellular carcinoma.  Blood Cells Mol Dis. 1999;  25 350-353
• 82 Fargion S, Stazi M A, Fracanzani A L et al.. Mutations in the HFE gene and their interaction with exogenous risk factors in hepatocellular carcinoma.  Blood Cells Mol Dis. 2001;  27 505-511
• 83 Hellerbrand C, Poppl A, Hartmann A, Scholmerich J, Lock G. HFE C282Y heterozygosity in hepatocellular carcinoma: evidence for an increased prevalence.  Clin Gastroenterol Hepatol. 2003;  1 279-284
• 84 Lauret E, Rodriguez M, Gonzalez S et al.. HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma.  Am J Gastroenterol. 2002;  97 1016-1021
• 85 Pirisi M, Toniutto P, Uzzau A et al.. Carriage of HFE mutations and outcome of surgical resection for hepatocellular carcinoma in cirrhotic patients.  Cancer. 2000;  89 297-302
• 86 Fargion S, Piperno A, Fracanzani A L, Cappellini M D, Romano R, Fiorelli G. Iron in the pathogenesis of hepatocellular carcinoma.  Ital J Gastroenterol. 1991;  23 584-588
• 87 Mallory M A, Kowdley K V. Hereditary hemochromatosis and cancer risk: more fuel to the fire?.  Gastroenterology. 2001;  121 1253-1254
• 88 Wang X W, Hussain S P, Huo T I et al.. Molecular pathogenesis of human hepatocellular carcinoma.  Toxicology. 2002;  181-182 43-47
• 89 Deugnier Y, Turlin B. Iron and hepatocellular carcinoma.  J Gastroenterol Hepatol. 2001;  16 491-494
• 90 Hatch M C, Chen C J, Levin B et al.. Urinary aflatoxin levels, hepatitis-B virus infection and hepatocellular carcinoma in Taiwan.  Int J Cancer. 1993;  54 931-934
• 91 Van Rensburg S J, Cook-Mozaffari P, Van Schalkwyk D J, Van der Watt J J, Vincent T J, Purchase I F. Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei.  Br J Cancer. 1985;  51 713-726
• 92 Yeh F S, Yu M C, Mo C C, Luo S, Tong M J, Henderson B E. Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China.  Cancer Res. 1989;  49 2506-2509
• 93 Omer R E, Kuijsten A, Kadaru A M et al.. Population-attributable risk of dietary aflatoxins and hepatitis B virus infection with respect to hepatocellular carcinoma.  Nutr Cancer. 2004;  48 15-21
• 94 Wang J S, Qian G S, Zarba A 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.  Cancer Epidemiol Biomarkers Prev. 1996;  5 253-261
• 95 Groopman J D. Do aflatoxin-DNA adduct measurements in humans provide accurate data for cancer risk assessment?.  IARC Sci Publ. 1988;  (89) 55-62
• 96 Chen C J, Wang L Y, Lu S N et al.. Elevated aflatoxin exposure and increased risk of hepatocellular carcinoma.  Hepatology. 1996;  24 38-42
• 97 Ross R K, Yuan J M, Yu M C et al.. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma.  Lancet. 1992;  339 943-946
• 98 Lin L, Yang F, Ye Z et al.. Case-control study of cigarette smoking and primary hepatoma in an aflatoxin-endemic region of China: a protective effect.  Pharmacogenetics. 1991;  1 79-85
• 99 Sun Z, Lu P, Gail M H et al.. Increased risk of hepatocellular carcinoma in male hepatitis B surface antigen carriers with chronic hepatitis who have detectable urinary aflatoxin metabolite M1.  Hepatology. 1999;  30 379-383
• 100 Wang L Y, Hatch M, Chen C J et al.. Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan.  Int J Cancer. 1996;  67 620-625
• 101 Kew M C. Synergistic interaction between aflatoxin B1 and hepatitis B virus in hepatocarcinogenesis.  Liver Int. 2003;  23 405-409
• 102 Wojnowski L, Turner P C, Pedersen B et al.. Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West Africa.  Pharmacogenetics. 2004;  14 691-700
• 103 Kubicka S, Trautwein C, Niehof M, Manns M. Target gene modulation in hepatocellular carcinomas by decreased DNA-binding of p53 mutations.  Hepatology. 1997;  25 867-873
• 104 Aguilar F, Hussain S P, Cerutti P. Aflatoxin B1 induces the transversion of G→T in codon 249 of the p53 tumor suppressor gene in human hepatocytes.  Proc Natl Acad Sci USA. 1993;  90 8586-8590
• 105 Hsu I C, Metcalf R A, Sun T, Welsh J A, Wang N J, Harris C C. Mutational hotspot in the p53 gene in human hepatocellular carcinomas.  Nature. 1991;  350 427-428
• 106 Kirk G D, Camus-Randon A M, Mendy M et al.. Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia.  J Natl Cancer Inst. 2000;  92 148-153
• 107 Adami H O, Chow W H, Nyren O et al.. Excess risk of primary liver cancer in patients with diabetes mellitus.  J Natl Cancer Inst. 1996;  88 1472-1477
• 108 Lu S N, Lin T M, Chen C J et al.. A case-control study of primary hepatocellular carcinoma in Taiwan.  Cancer. 1988;  62 2051-2055
• 109 Lawson D H, Gray J M, McKillop C, Clarke J, Lee F D, Patrick R S. Diabetes mellitus and primary hepatocellular carcinoma.  Q J Med. 1986;  61 945-955
• 110 Matsuo M. Association between diabetes mellitus and hepatocellular carcinoma: results of a hospital- and community-based case-control study.  Kurume Med J. 2003;  50 91-98
• 111 Regimbeau J M, Colombat M, Mognol P et al.. Obesity and diabetes as a risk factor for hepatocellular carcinoma.  Liver Transpl. 2004;  10 S69-S73
• 112 El-Serag H B, Tran T, Everhart J E. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma.  Gastroenterology. 2004;  126 460-468
• 113 Lagiou P, Kuper H, Stuver S O, Tzonou A, Trichopoulos D, Adami H O. Role of diabetes mellitus in the etiology of hepatocellular carcinoma.  J Natl Cancer Inst. 2000;  92 1096-1099
• 114 Tolman K G, Fonseca V, Tan M H, Dalpiaz A. Narrative review: hepatobiliary disease in type 2 diabetes mellitus.  Ann Intern Med. 2004;  141 946-956
• 115 Tazawa J, Maeda M, Nakagawa M et al.. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C.  Dig Dis Sci. 2002;  47 710-715
• 116 IARC Working Group on the Evaluation of Carcinogenic Risks to Humans . Tobacco smoke and involuntary smoking.  IARC Monogr Eval Carcinog Risks Hum. 2004;  83 1-1438
• 117 Trichopoulos D, Day N E, Kaklamani E et al.. Hepatitis B virus, tobacco smoking and ethanol consumption in the etiology of hepatocellular carcinoma.  Int J Cancer. 1987;  39 45-49
• 118 Trichopoulos D, MacMahon B, Sparros L, Merikas G. Smoking and hepatitis B-negative primary hepatocellular carcinoma.  J Natl Cancer Inst. 1980;  65 111-114
• 119 Lam K C, Yu M C, Leung J W, Henderson B E. Hepatitis B virus and cigarette smoking: risk factors for hepatocellular carcinoma in Hong Kong.  Cancer Res. 1982;  42 5246-5248
• 120 Gelatti U, Covolo L, Talamini R et al.. N-Acetyltransferase-2, glutathione S-transferase M1 and T1 genetic polymorphisms, cigarette smoking and hepatocellular carcinoma: a case-control study.  Int J Cancer. 2005;  115 301-306
• 121 Mori M, Hara M, Wada I 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.  Am J Epidemiol. 2000;  151 131-139
• 122 Pyong S J, Tsukuma H, Hiyama T. Case-control study of hepatocellular carcinoma among Koreans living in Osaka, Japan.  Jpn J Cancer Res. 1994;  85 674-679
• 123 Shin H R, Lee C U, Park H J et al.. Hepatitis B and C virus, Clonorchis sinensis for the risk of liver cancer: a case-control study in Pusan, Korea.  Int J Epidemiol. 1996;  25 933-940
• 124 Tsukuma H, Hiyama T, Tanaka S et al.. Risk factors for hepatocellular carcinoma among patients with chronic liver disease.  N Engl J Med. 1993;  328 1797-1801
• 125 Oshima A, Tsukuma H, Hiyama T, Fujimoto I, Yamano H, Tanaka M. Follow-up study of HBs Ag-positive blood donors with special reference to effect of drinking and smoking on development of liver cancer.  Int J Cancer. 1984;  34 775-779
• 126 Chiba T, Matsuzaki Y, Abei M et al.. The role of previous hepatitis B virus infection and heavy smoking in hepatitis C virus-related hepatocellular carcinoma.  Am J Gastroenterol. 1996;  91 1195-1203
• 127 Chen S Y, Wang L Y, Lunn R M et al.. Polycyclic aromatic hydrocarbon-DNA adducts in liver tissues of hepatocellular carcinoma patients and controls.  Int J Cancer. 2002;  99 14-21
• 128 Yu M W, Pai C I, Yang S Y et al.. Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk.  Gut. 2000;  47 703-709
• 129 Younossi Z M, McCullough A J, Ong J P et al.. Obesity and non-alcoholic fatty liver disease in chronic hepatitis C.  J Clin Gastroenterol. 2004;  38 705-709
• 130 Anagnostopoulos G K, Arvanitidis D, Tsiakos S, Margantinis G, Grigoriadis K, Kostopoulos P. Is hepatocellular carcinoma part of the natural history of nonalcoholic steatohepatitis?.  J Clin Gastroenterol. 2003;  37 88-89
• 131 Bencheqroun R, Duvoux C, Luciani A, Zafrani E S, Dhumeaux D. [Hepatocellular carcinoma without cirrhosis in a patient with nonalcoholic steatohepatitis].  Gastroenterol Clin Biol. 2004;  28 497-499
• 132 Bullock R E, Zaitoun A M, Aithal G P, Ryder S D, Beckingham I J, Lobo D N. Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma.  J Hepatol. 2004;  41 685-686
• 133 Cuadrado A, Orive A, Garcia-Suarez C et al.. Non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma.  Obes Surg. 2005;  15 442-446
• 134 Marrero J A, Fontana R J, Su G L, Conjeevaram H S, Emick D M, Lok A S. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States.  Hepatology. 2002;  36 1349-1354
• 135 Mori S, Yamasaki T, Sakaida I et al.. Hepatocellular carcinoma with nonalcoholic steatohepatitis.  J Gastroenterol. 2004;  39 391-396
• 136 Orikasa H, Ohyama R, Tsuka N, Eyden B P, Yamazaki K. Lipid-rich clear-cell hepatocellular carcinoma arising in non-alcoholic steatohepatitis in a patient with diabetes mellitus.  J Submicrosc Cytol Pathol. 2001;  33 195-200
• 137 Shimada M, Hashimoto E, Taniai M et al.. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis.  J Hepatol. 2002;  37 154-160
• 138 Yoshioka Y, Hashimoto E, Yatsuji S et al.. Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH.  J Gastroenterol. 2004;  39 1215-1218
• 139 Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, Nakanuma Y. Hepatocellular carcinoma arising in non-alcoholic steatohepatitis.  Pathol Int. 2001;  51 127-131
• 140 Hashimoto E, Taniai M, Kaneda H et al.. Comparison of hepatocellular carcinoma patients with alcoholic liver disease and nonalcoholic steatohepatitis.  Alcohol Clin Exp Res. 2004;  28 164S-168S
• 141 Yang S, Lin H Z, Hwang J, Chacko V P, Diehl A M. Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?.  Cancer Res. 2001;  61 5016-5023
• 142 Lonardo A, Bagni A, Tarugi P, Loria P. The wide spectrum of steatohepatitis: a report of four cases and a review of the literature.  Eur J Gastroenterol Hepatol. 2004;  16 1043-1050
• 143 Nair S, Mason A, Eason J, Loss G, Perrillo R P. Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?.  Hepatology. 2002;  36 150-155
• 144 Ratziu V, Bonyhay L, Di Martino V et al.. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis.  Hepatology. 2002;  35 1485-1493
• 145 Caldwell S H, Crespo D M, Kang H S, Al-Osaimi A M. Obesity and hepatocellular carcinoma.  Gastroenterology. 2004;  127 S97-103
• 146 Huo T I, Wu J C, Lee S D. Are alcohol, tobacco and obesity genuine risk factors for hepatocellular carcinoma?.  J Hepatol. 2005;  42 941
• 147 Suriawinata A, Fiel M I. Liver pathology in obesity.  Semin Liver Dis. 2004;  24 363-370
• 148 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. 2001;  12 959-964
• 149 Parkin D M, Ohshima H, Srivatanakul P, Vatanasapt V. Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.  Cancer Epidemiol Biomarkers Prev. 1993;  2 537-544
• 150 Shaib Y H, El-Serag H B, Davila J A, Morgan R, McGlynn K A. Risk factors of intrahepatic cholangiocarcinoma in the United States: a case-control study.  Gastroenterology. 2005;  128 620-626
• 151 Kuper H, Lagiou P, Mucci L A, Tamimi R, Benetou V, Trichopoulos D. Risk factors for cholangiocarcinoma in a low risk Caucasian population.  Soz Praventivmed. 2001;  46 182-185
• 152 Parkin D M, Srivatanakul P, Khlat M et al.. Liver cancer in Thailand. I: a case-control study of cholangiocarcinoma.  Int J Cancer. 1991;  48 323-328
• 153 Sorensen H T, Friis S, Olsen J H et al.. Risk of liver and other types of cancer in patients with cirrhosis: a nationwide cohort study in Denmark.  Hepatology. 1998;  28 921-925
• 154 Altaee M Y, Johnson P J, Farrant J M, Williams R. Etiologic and clinical characteristics of peripheral and hilar cholangiocarcinoma.  Cancer. 1991;  68 2051-2055
• 155 Su W C, Chan K K, Lin X Z et al.. A clinical study of 130 patients with biliary tract cancers and periampullary tumors.  Oncology. 1996;  53 488-493
• 156 Pinyosophon A, Wiwanitkit V. The prevalence of hepatitis B seropositivity among patients with cholangiocarcinoma.  Viral Immunol. 2002;  15 655-657
• 157 Songsivilai S, Dharakul T, Kanistanon D. Hepatitis C virus genotypes in patients with hepatocellular carcinoma and cholangiocarcinoma in Thailand.  Trans R Soc Trop Med Hyg. 1996;  90 505-507
• 158 Yamamoto S, Kubo S, Hai S et al.. Hepatitis C virus infection as a likely etiology of intrahepatic cholangiocarcinoma.  Cancer Sci. 2004;  95 592-595
• 159 Kobayashi M, Ikeda K, Saitoh S et al.. Incidence of primary cholangiocellular carcinoma of the liver in Japanese patients with hepatitis C virus-related cirrhosis.  Cancer. 2000;  88 2471-2477
• 160 Lu H, Ye M Q, Thung S N, Dash S, Gerber M A. Detection of hepatitis C virus RNA sequences in cholangiocarcinomas in Chinese and American patients.  Chin Med J (Engl). 2000;  113 1138-1141
• 161 Polizos A, Kelekis N, Sinani C, Patsiaoura K, Papadamou G, Dalekos G N. Advanced intrahepatic cholangiocarcinoma in hepatitis C virus-related decompensated cirrhosis: case report and review of the literature.  Eur J Gastroenterol Hepatol. 2003;  15 331-334
• 162 Bergquist A, Ekbom A, Olsson R et al.. Hepatic and extrahepatic malignancies in primary sclerosing cholangitis.  J Hepatol. 2002;  36 321-327
• 163 Boberg K M, Bergquist A, Mitchell S et al.. Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation.  Scand J Gastroenterol. 2002;  37 1205-1211
• 164 Broome U, Olsson R, Loof L et al.. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.  Gut. 1996;  38 610-615
• 165 Burak K, Angulo P, Pasha T M, Egan K, Petz J, Lindor K D. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis.  Am J Gastroenterol. 2004;  99 523-526
• 166 Ponsioen C Y, Vrouenraets S M, Prawirodirdjo W et al.. Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population.  Gut. 2002;  51 562-566
• 167 Bjornsson E, Boberg K M, Cullen S et al.. Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis.  Gut. 2002;  51 731-735
• 168 Boberg K M, Schrumpf E, Bergquist A et al.. Cholangiocarcinoma in primary sclerosing cholangitis: K-ras mutations and Tp53 dysfunction are implicated in the neoplastic development.  J Hepatol. 2000;  32 374-380
• 169 Boberg K M, Spurkland A, Rocca G et al.. The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis.  Scand J Gastroenterol. 2001;  36 886-890
• 170 Bergquist A, Glaumann H, Persson B, Broome U. Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case-control study.  Hepatology. 1998;  27 311-316
• 171 Chalasani N, Baluyut A, Ismail A et al.. Cholangiocarcinoma in patients with primary sclerosing cholangitis: a multicenter case-control study.  Hepatology. 2000;  31 7-11
• 172 Kornfeld D, Ekbom A, Ihre T. Survival and risk of cholangiocarcinoma in patients with primary sclerosing cholangitis: a population-based study.  Scand J Gastroenterol. 1997;  32 1042-1045
• 173 International Agency for Research on Cancer Working Group . Infection with liver flukes (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis).  IARC Monogr Eval Carcinog Risks Hum. 1994;  61 121-175
• 174 Schwartz D A. Cholangiocarcinoma associated with liver fluke infection: a preventable source of morbidity in Asian immigrants.  Am J Gastroenterol. 1986;  81 76-79
• 175 Stauffer W M, Sellman J S, Walker P F. Biliary liver flukes (Opisthorchiasis and Clonorchiasis) in immigrants in the United States: often subtle and diagnosed years after arrival.  J Travel Med. 2004;  11 157-159
• 176 Chapman R W. Risk factors for biliary tract carcinogenesis.  Ann Oncol. 1999;  10(suppl 4) 308-311
• 177 Choi B I, Han J K, Hong S T, Lee K H. Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis.  Clin Microbiol Rev. 2004;  17 540-552
• 178 Hong S T, Kho W G, Kim W H, Chai J Y, Lee S H. Turnover of biliary epithelial cells in Clonorchis sinensis infected rats.  Korean J Parasitol. 1993;  31 83-89
• 179 Hou P C. The relationship between primary carcinoma of the liver and infestation with Clonorchis sinensis .  J Pathol Bacteriol. 1956;  72 239-246
• 180 Sriamporn S, Pisani P, Pipitgool V, Suwanrungruang K, Kamsa-ard S, Parkin D M. Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand.  Trop Med Int Health. 2004;  9 588-594
• 181 Pairojkul C, Shirai T, Hirohashi S et al.. Multistage carcinogenesis of liver-fluke-associated cholangiocarcinoma in Thailand.  Princess Takamatsu Symp. 1991;  22 77-86
• 182 Haswell-Elkins M R, Mairiang E, Mairiang P et al.. Cross-sectional study of Opisthorchis viverrini infection and cholangiocarcinoma in communities within a high-risk area in northeast Thailand.  Int J Cancer. 1994;  59 505-509
• 183 Itoh M, Pairojkul C, Thamawit W et al.. Association of antibodies to Opisthorchis viverrini with hepatobiliary disease in northeastern Thailand.  Am J Trop Med Hyg. 1994;  51 424-429
• 184 Pinlaor S, Hiraku Y, Ma N et al.. Mechanism of NO-mediated oxidative and nitrative DNA damage in hamsters infected with Opisthorchis viverrini: a model of inflammation-mediated carcinogenesis.  Nitric Oxide. 2004;  11 175-183
• 185 Pinlaor S, Tada-Oikawa S, Hiraku Y et al.. Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in macrophage RAW cell line.  Int J Parasitol. 2005;  35 591-596
• 186 Lee C C, Wu C Y, Chen G H. What is the impact of coexistence of hepatolithiasis on cholangiocarcinoma?.  J Gastroenterol Hepatol. 2002;  17 1015-1020
• 187 Chen D W, Tung-Ping Poon R, Liu C L, Fan S T, Wong J. Immediate and long-term outcomes of hepatectomy for hepatolithiasis.  Surgery. 2004;  135 386-393
• 188 Chen M F, Jan Y Y, Wang C S et al.. A reappraisal of cholangiocarcinoma in patient with hepatolithiasis.  Cancer. 1993;  71 2461-2465
• 189 Chijiiwa K, Ohtani K, Noshiro H et al.. Cholangiocellular carcinoma depending on the kind of intrahepatic calculi in patients with hepatolithiasis.  Hepatogastroenterology. 2002;  49 96-99
• 190 Wang Y J, Lee S D, Shyu J K, Lo K J. Clinical experience in 126 patients with tissue-proved proximal cholangiocarcinoma.  J Gastroenterol Hepatol. 1994;  9 134-137
• 191 Lesurtel M, Regimbeau J M, Farges O, Colombat M, Sauvanet A, Belghiti J. Intrahepatic cholangiocarcinoma and hepatolithiasis: an unusual association in Western countries.  Eur J Gastroenterol Hepatol. 2002;  14 1025-1027
• 192 Lee K T, Liu T S. Expression of transforming growth factor betas and their signaling receptors in stone-containing intrahepatic bile ducts and cholangiocarcinoma.  World J Surg. 2003;  27 1143-1148
• 193 Terada T, Ashida K, Endo K et al.. c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma.  Histopathology. 1998;  33 325-331
• 194 Liu D, Momoi H, Li L, Ishikawa Y, Fukumoto M. Microsatellite instability in thorotrast-induced human intrahepatic cholangiocarcinoma.  Int J Cancer. 2002;  102 366-371
• 195 Sharp G B. The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data.  J Radiat Res (Tokyo). 2002;  43 371-380
• 196 Yamada S, Hosoda S, Tateno H, Kido C, Takahashi S. Survey of thorotrast-associated liver cancers in Japan.  J Natl Cancer Inst. 1983;  70 31-35
• 197 Lipsett P A, Pitt H A, Colombani P M, Boitnott J K, Cameron J L. Choledochal cyst disease: a changing pattern of presentation.  Ann Surg. 1994;  220 644-652
• 198 Nakeeb A, Pitt H A, Sohn T A et al.. Cholangiocarcinoma: a spectrum of intrahepatic, perihilar, and distal tumors.  Ann Surg. 1996;  224 463-473 , discussion 473-5
• 199 de Vries J S, de Vries S, Aronson D C et al.. Choledochal cysts: age of presentation, symptoms, and late complications related to Todani's classification.  J Pediatr Surg. 2002;  37 1568-1573
• 200 Goto N, Yasuda I, Uematsu T et al.. Intrahepatic cholangiocarcinoma arising 10 years after the excision of congenital extrahepatic biliary dilation.  J Gastroenterol. 2001;  36 856-862
• 201 DiBisceglie A M. Malignant neoplasms of the liver. In: Schiff ER, Sorrell MF, Maddrey WC Schiff's Diseases of the Liver. 8th ed. Philadelphia; Lippincott Raven 1999: 1294
• 202 Saab S, Yao F. Fibrolamellar hepatocellular carcinoma: case reports and a review of the literature.  Dig Dis Sci. 1996;  41 1981-1985
• 203 El-Serag H B, Davila J A. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study.  Hepatology. 2004;  39 798-803
• 204 Sooklim K, Sriplung H, Piratvisuth T. Histologic subtypes of hepatocellular carcinoma in the southern Thai population.  Asian Pac J Cancer Prev. 2003;  4 302-306
• 205 Dadke D, Jaganath P, Krishnamurthy S, Chiplunkar S. The detection of HBV antigens and HBx-transcripts in an Indian fibrolamellar carcinoma patient: a case study.  Liver. 2002;  22 87-91
• 206 Fong Y, Kemeny N, Lawrence T S. Cancer of the liver and biliary tree. In: Devita VT, Hellman S, Rosenberg SA Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia; Lippincott Williams and Wilkins 2001: 1177-1178
• 207 Lee C L, Ko Y C. Survival and distribution pattern of childhood liver cancer in Taiwan.  Eur J Cancer. 1998;  34 2064-2067
• 208 Bortolasi L, Marchiori L, Dal Dosso I, Colombari R, Nicoli N. Hepatoblastoma in adult age: a report of two cases.  Hepatogastroenterology. 1996;  43 1073-1078
• 209 Bunin G R. Nongenetic causes of childhood cancers: evidence from international variation, time trends, and risk factor studies.  Toxicol Appl Pharmacol. 2004;  199 91-103
• 210 Feusner J, Plaschkes J. Hepatoblastoma and low birth weight: a trend or chance observation?.  Med Pediatr Oncol. 2002;  39 508-509
• 211 Ikeda H, Matsuyama S, Tanimura M. Association between hepatoblastoma and very low birth weight: a trend or a chance?.  J Pediatr. 1997;  130 557-560
• 212 DiBisceglie A M. Malignant neoplasms of the liver. In: Schiff ER, Sorrell MF, Maddrey WC Schiff's Diseases of the Liver. 8th ed. Philadelphia; Lippincott Raven 1999: 1281-1304
• 213 Mani H, Van Thiel D H. Mesenchymal tumors of the liver.  Clin Liver Dis. 2001;  5 219-257 , viii
• 214 Molina E, Hernandez A. Clinical manifestations of primary hepatic angiosarcoma.  Dig Dis Sci. 2003;  48 677-682
• 215 Falk H, Herbert J, Crowley S et al.. Epidemiology of hepatic angiosarcoma in the United States: 1964-1974.  Environ Health Perspect. 1981;  41 107-113
• 216 Hozo I, Miric D, Bojic L et al.. Liver angiosarcoma and hemangiopericytoma after occupational exposure to vinyl chloride monomer.  Environ Health Perspect. 2000;  108 793-795
• 217 Kielhorn J, Melber C, Wahnschaffe U, Aitio A, Mangelsdorf I. Vinyl chloride: still a cause for concern.  Environ Health Perspect. 2000;  108 579-588
• 218 Lee F I, Smith P M, Bennett B, Williams D M. Occupationally related angiosarcoma of the liver in the United Kingdom 1972-1994.  Gut. 1996;  39 312-318
• 219 Falk H, Caldwell G G, Ishak K G, Thomas L B, Popper H. Arsenic-related hepatic angiosarcoma.  Am J Ind Med. 1981;  2 43-50
• 220 Roat J W, Wald A, Mendelow H, Pataki K I. Hepatic angiosarcoma associated with short-term arsenic ingestion.  Am J Med. 1982;  73 933-936
• 221 Ito Y, Kojiro M, Nakashima T, Mori T. Pathomorphologic characteristics of 102 cases of thorotrast-related hepatocellular carcinoma, cholangiocarcinoma, and hepatic angiosarcoma.  Cancer. 1988;  62 1153-1162
• 222 Przygodzki R M, Finkelstein S D, Keohavong P et al.. Sporadic and thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2.  Lab Invest. 1997;  76 153-159
• 223 Falk H, Thomas L B, Popper H, Ishak K G. Hepatic angiosarcoma associated with androgenic-anabolic steroids.  Lancet. 1979;  2 1120-1123
• 224 Rosenthal A K, Klausmeier M, Cronin M E, McLaughlin J K. Hepatic angiosarcoma occurring after cyclophosphamide therapy: case report and review of the literature.  Am J Clin Oncol. 2000;  23 581-583
• 225 DiBisceglie A M. Malignant neoplasms of the liver. In: Schiff ER, Sorrell MF, Maddrey WC Schiff's Diseases of the Liver. 8th ed. Philadelphia; Lippincott Raven 1999: 1300
• 226 Ayoub J P, Hess K R, Abbruzzese M C, Lenzi R, Raber M N, Abbruzzese J L. Unknown primary tumors metastatic to liver.  J Clin Oncol. 1998;  16 2105-2112
• 227 Kew M C. Hepatic tumors and cysts. In: Feldman M, Friedman LS, Sleisenger MH, Scharschmidt BF Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/ Management. 7th ed. Philadelphia; Saunders 2002: 1589-1590
• 228 Hoe A L, Royle G T, Taylor I. Breast liver metastases: incidence, diagnosis and outcome.  J R Soc Med. 1991;  84 714-716
• 229 Gorog D, Toth A, Weltner J. Prognosis of untreated liver metastasis from rectal cancer.  Acta Chir Hung. 1997;  36 106-107
• 230 Alexander H R, Allegra C J, Lawrence T S. Metastatic cancer to the liver. In: Devita VT, Hellman S, Rosenberg SA Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia; Lippincott Williams and Wilkins 2001: 2690
• 231 Ferlito A, Shaha A R, Silver C E, Rinaldo A, Mondin V. Incidence and sites of distant metastases from head and neck cancer.  ORL J Otorhinolaryngol Relat Spec. 2001;  63 202-207
• 232 Bralet M, Regimbeau J, Pineau P et al.. Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases.  Hepatology. 2000;  32 200-204