Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it?

World Journal of Gastroenterology

Volumn 19, Issue 47, 2013, Pages 8808-8821

  Giannini, Edoardo G ^a   Cucchetti, Alessandro ^b   Erroi, Virginia ^b   Garuti, Francesca ^c   Odaldi, Federica ^c   Trevisani, Franco ^c  

^a UNIVERSITY OF GENOA   (Italy)

^b Dipartimento di Scien ze Mediche Chirurgiche   (Italy)

^c UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Cost effectiveness; Hepatocellular carcinoma; Screening; Surveillance; Ultrasonography

Indexed keywords

ALPHA FETOPROTEIN; PROTHROMBIN;

ARTICLE; BILE DUCT CARCINOMA; BIOPSY; CHRONIC LIVER DISEASE; CLINICAL PRACTICE; COMPUTER ASSISTED TOMOGRAPHY; COST EFFECTIVENESS ANALYSIS; DISEASE SURVEILLANCE; ECHOGRAPHY; FOLLOW UP; HEALTH EDUCATION; HEPATITIS B; HEPATITIS C; HUMAN; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER TRANSPLANTATION; MORBIDITY; MORTALITY; NUCLEAR MAGNETIC RESONANCE; RANDOMIZED CONTROLLED TRIAL (TOPIC); SENSITIVITY AND SPECIFICITY; THROMBOCYTOPENIA;

COST-EFFECTIVENESS; HEPATOCELLULAR CARCINOMA; SCREENING; SURVEILLANCE; ULTRASONOGRAPHY;

CARCINOMA, HEPATOCELLULAR; COST-BENEFIT ANALYSIS; EARLY DETECTION OF CANCER; HEALTH CARE COSTS; HUMANS; LIVER NEOPLASMS; NEOPLASM STAGING; PATIENT SELECTION; POPULATION SURVEILLANCE; PREDICTIVE VALUE OF TESTS; RISK ASSESSMENT; RISK FACTORS; TIME FACTORS;

EID: 84890911154     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v19.i47.8808     Document Type: Article

References (122)

1. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol 2001; 2: 533-543[PMID: 11905707 DOI: 10.1016/ S1470-2045(01)00486-7]
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBO-CAN 2008. Int J Cancer 2010; 127: 2893-2917[PMID: 21351269 DOI: 10.1002/ijc.25516]
3. de Lope CR, Tremosini S, Forner A, Reig M, Bruix J. Management of HCC. J Hepatol 2012; 56 Suppl 1: S75-S87[PMID: 22300468 DOI: 10.1016/S0168-8278(12)60009-9]
4. Noda I, Kitamoto M, Nakahara H, Hayashi R, Okimoto T, Monzen Y, Yamada H, Imagawa M, Hiraga N, Tanaka J, Chayama K. Regular surveillance by imaging for early detection and better prognosis of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol 2010; 45: 105-112[PMID: 19866332 DOI: 10.1007/s00535-009-0131-x]
5. Lederle FA, Pocha C. Screening for liver cancer: the rush to judgment. Ann Intern Med 2012; 156: 387-389[PMID: 22393134 DOI: 10.7326/0003-4819-156-5-201203060-00012]
6. Prorok PC. Epidemiologic approach for cancer screening. Problems in design and analysis of trials. Am J Pediatr Hematol Oncol 1992; 14: 117-128[PMID: 1530116]
7. El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 2004; 127: S27-S34[PMID: 15508094 DOI: 10.1053/j.gastro.2004.09.013]
8. Kanwal F, Hoang T, Kramer JR, Asch SM, Goetz MB, Zeringue A, Richardson P, El-Serag HB. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology 2011; 140: 1182-1188.e1[PMID: 21184757 DOI: 10.1053/j.gastro.2010.12.032]
9. Benvegnù L, Gios M, Boccato S, Alberti A. Natural history of compensated viral cirrhosis: a prospective study on the incidence and hierarchy of major complications. Gut 2004; 53: 744-749[PMID: 15082595 DOI: 10.1136/gut.2003.020263]
10. Talwalkar JA, Kamath PS. Infuence of recent advances in medical management on clinical outcomes of cirrhosis. Mayo Clin Proc 2005; 80: 1501-1508[PMID: 16295030 DOI: 10.4065/80.11.1501]
11. Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E, La Vecchia C. Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004. Hepatology 2008; 48: 137-145[PMID: 18537177 DOI: 10.1002/hep.22312]
12. Bosetti C, Bianchi C, Negri E, Colombo M, La Vecchia C. Estimates of the incidence and prevalence of hepatocellular carcinoma in Italy in 2002 and projections for the years 2007 and 2012. Tumori 2009; 95: 23-27[PMID: 19366051]
13. Bertuccio P, Bosetti C, Levi F, Decarli A, Negri E, La Vecchia C. A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe. Ann Oncol 2013; 24: 1667-1674[PMID: 23378539 DOI: 10.1093/an-nonc/mds652]
14. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroen-terology 2004; 127: S35-S50[PMID: 15508101 DOI: 10.1053/ j.gastro.2004.09.014]
15. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020-1022[PMID: 21374666 DOI: 10.1002/hep.24199]
16. European Association For The Study Of The Liver; European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocel-lular carcinoma. J Hepatol 2012; 56: 908-943[PMID: 22424438 DOI: 10.1016/j.jhep.2011.12.001]
17. Bolondi L. Screening for hepatocellular carcinoma in cirrhosis. J Hepatol 2003; 39: 1076-1084[PMID: 14642630 DOI: 10.1016/S0168-8278(03)00349-0]
18. Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA, Marrero JA. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther 2009; 30: 37-47[PMID: 19392863 DOI: 10.1111/j.1365-2036.2009.04014.x]
19. Bolondi L, Sofa S, Siringo S, Gaiani S, Casali A, Zironi G, Piscaglia F, Gramantieri L, Zanetti M, Sherman M. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut 2001; 48: 251-259[PMID: 11156649 DOI: 10.1136/gut.48.2.251]
20. Sangiovanni A, Manini MA, Iavarone M, Romeo R, Forzeni-go LV, Fraquelli M, Massironi S, Della Corte C, Ronchi G, Rumi MG, Biondetti P, Colombo M. The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis. Gut 2010; 59: 638-644[PMID: 19951909 DOI: 10.1136/gut.2009.187286]
21. Lee JM, Trevisani F, Vilgrain V, Wald C. Imaging diagnosis and staging of hepatocellular carcinoma. Liver Transpl 2011; 17 Suppl 2: S34-S43[PMID: 21739567 DOI: 10.1002/lt.22369]
22. Sherman M. Current status of alpha-fetoprotein testing. Gas-troenterol Hepatol (N Y) 2011; 7: 113-114[PMID: 21475418]
23. Giannini EG, Marenco S, Borgonovo G, Savarino V, Farinati F, Del Poggio P, Rapaccini GL, Anna Di Nolfo M, Benvegnù L, Zoli M, Borzio F, Caturelli E, Chiaramonte M, Trevisani F. Alpha-fetoprotein has no prognostic role in small hepatocel-lular carcinoma identifed during surveillance in compensated cirrhosis. Hepatology 2012; 56: 1371-1379[PMID: 22535689 DOI: 10.1002/hep.25814]
24. Trevisani F, De Notariis S, Rapaccini G, Farinati F, Benvegnù L, Zoli M, Grazi GL, Del PP, Di N, Bernardi M. Semiannual and annual surveillance of cirrhotic patients for hepatocel-lular carcinoma: effects on cancer stage and patient survival (Italian experience). Am J Gastroenterol 2002; 97: 734-744[PMID: 11922571 DOI: 10.1111/j.1572-0241.2002.05557.x]
25. Zhang B, Yang B. Combined alpha fetoprotein testing and ultrasonography as a screening test for primary liver cancer. J Med Screen 1999; 6: 108-110[PMID: 10444731 DOI: 10.1136/ jms.6.2.108]
26. Davila JA, Morgan RO, Richardson PA, Du XL, McGlynn KA, El-Serag HB. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States. Hepatology 2010; 52: 132-141[PMID: 20578139 DOI: 10.1002/hep.23615]
27. El-Serag HB, Kramer JR, Chen GJ, Duan Z, Richardson PA, Davila JA. Effectiveness of AFP and ultrasound tests on he-patocellular carcinoma mortality in HCV-infected patients in the USA. Gut 2011; 60: 992-997[PMID: 21257990 DOI: 10.1136/gut.2010.230508]
28. Singal AG, Nehra M, Adams-Huet B, Yopp AC, Tiro JA, Mar-rero JA, Lok AS, Lee WM. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol 2013; 108: 425-432PMID: 23337478 DOI: 10.1038/ajg.2012.449]
29. Giannini EG, Trevisani F. Surveillance for hepatocellular carcinoma: just do it! Am J Gastroenterol 2013; 108: 1013-1014[PMID: 23735924 DOI: 10.1038/ajg.2013.98]
30. Forner A, Vilana R, Ayuso C, Bianchi L, Solé M, Ayuso JR, Boix L, Sala M, Varela M, Llovet JM, Brú C, Bruix J. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology 2008; 47: 97-104[PMID: 18069697 DOI: 10.1002/hep.21966]
31. Leoni S, Piscaglia F, Golfieri R, Camaggi V, Vidili G, Pini P, Bolondi L. The impact of vascular and nonvascular fnd-ings on the noninvasive diagnosis of small hepatocellular carcinoma based on the EASL and AASLD criteria. Am J Gas-troenterol 2010; 105: 599-609[PMID: 19935786 DOI: 10.1038/ ajg.2009.654]
32. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 2004; 130: 417-422[PMID: 15042359 DOI: 10.1007/ s00432-004-0552-0]
33. Stravitz RT, Heuman DM, Chand N, Sterling RK, Shiffman ML, Luketic VA, Sanyal AJ, Habib A, Mihas AA, Giles HC, Maluf DG, Cotterell AH, Posner MP, Fisher RA. Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome. Am J Med 2008; 121: 119-126[PMID: 18261500 DOI: 10.1016/j.amjmed.2007.09.020]
34. Santi V, Trevisani F, Gramenzi A, Grignaschi A, Mirici-Cappa F, Del Poggio P, Di Nolfo MA, Benvegnù L, Farinati F, Zoli M, Giannini EG, Borzio F, Caturelli E, Chiaramonte M, Bernardi M. Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival. J Hepatol 2010; 53: 291-297[PMID: 20483497 DOI: 10.1016/j.jhep.2010.03.010]
35. Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R, Morabito A, De Franchis R, Colombo M. Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology 2004; 126: 1005-1014[PMID: 15057740 DOI: 10.1053/j.gastro.2003.12.049]
36. Chen JG, Parkin DM, Chen QG, Lu JH, Shen QJ, Zhang BC, Zhu YR. Screening for liver cancer: results of a randomised controlled trial in Qidong, China. J Med Screen 2003; 10: 204-209[PMID: 14738659 DOI: 10.1258/096914103771773320]
37. Poustchi H, Farrell GC, Strasser SI, Lee AU, McCaughan GW, George J. Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed? Hepatology 2011; 54: 1998-2004[PMID: 21800340 DOI: 10.1002/hep.24581]
38. Sherman M, Bruix J, Porayko M, Tran T. Screening for hepato-cellular carcinoma: the rationale for the American Association for the Study of Liver Diseases recommendations. Hepatology 2012; 56: 793-796[PMID: 22689409 DOI: 10.1002/hep.25869]
39. Kuo YH, Lu SN, Chen CL, Cheng YF, Lin CY, Hung CH, Chen CH, Changchien CS, Hsu HC, Hu TH, Lee CM, Wang JH. Hepatocellular carcinoma surveillance and appropriate treatment options improve survival for patients with liver cirrhosis. Eur J Cancer 2010; 46: 744-751[PMID: 20060710 DOI: 10.1016/ j.ejca.2009.12.018]
40. Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Na-kashima O, Kojiro M, Makuuchi M. Management of hepato-cellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis 2011; 29: 339-364[PMID: 21829027 DOI: 10.1159/000327577]
41. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesopha-geal varices. Br J Surg 1973; 60: 646-649[PMID: 4541913]
42. Trevisani F, Santi V, Gramenzi A, Di Nolfo MA, Del Poggio P, Benvegnù L, Rapaccini G, Farinati F, Zoli M, Borzio F, Giannini EG, Caturelli E, Bernardi M. Surveillance for early diagnosis of hepatocellular carcinoma: is it effective in intermediate/advanced cirrhosis? Am J Gastroenterol 2007; 102: 2448-2457; quiz 2458[PMID: 17617210 DOI: 10.1111/j.1572-0241.2007.01395.x]
43. Laupacis A, Feeny D, Detsky AS, Tugwell PX. How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ 1992; 146: 473-481[PMID: 1306034]
44. Sarasin FP, Giostra E, Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med 1996; 101: 422-434[PMID: 8873514 DOI: 10.1016/S0002-9343(96)00197-0]
45. Gomez EV, Rodriguez YS, Bertot LC, Gonzalez AT, Perez YM, Soler EA, Garcia AY, Blanco LP. The natural history of compensated HCV-related cirrhosis: a prospective long-term study. J Hepatol 2013; 58: 434-444[PMID: 23111008 DOI: 10.1016/ j.jhep.2012.10.023]
46. Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010; 51: 1972-1978[PMID: 20209604 DOI: 10.1002/hep.23527]
47. Mancebo A, González-Diéguez ML, Cadahía V, Varela M, Pérez R, Navascués CA, Sotorríos NG, Martínez M, Rodrigo L, Rodríguez M. Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identifcation of risk groups. Clin Gastroenterol Hepatol 2013; 11: 95-101[PMID: 22982095 DOI: 10.1016/j.cgh.2012.09.007]
48. Caballería L, Parés A, Castells A, Ginés A, Bru C, Rodés J. Hepatocellular carcinoma in primary biliary cirrhosis: similar incidence to that in hepatitis C virus-related cirrhosis. Am J Gastroenterol 2001; 96: 1160-1163[PMID: 11316164 DOI: 10.1111/j.1572-0241.2001.03695.x]
49. Fracanzani AL, Conte D, Fraquelli M, Taioli E, Mattioli M, Losco A, Fargion S. 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[PMID: 11230745]
50. Yeoman AD, Al-Chalabi T, Karani JB, Quaglia A, Devlin J, Mie-li-Vergani G, Bomford A, O'Grady JG, Harrison PM, Heneghan MA. Evaluation of risk factors in the development of hepatos-cellular carcinoma in autoimmune hepatitis: Implications for follow-up and screening. Hepatology 2008; 48: 863-870[PMID: 18752332 DOI: 10.1002/hep.22432]
51. Bruno S, Stroffolini T, Colombo M, Bollani S, Benvegnù L, Mazzella G, Ascione A, Santantonio T, Piccinino F, Andreone P, Mangia A, Gaeta GB, Persico M, Fagiuoli S, Almasio PL. Sustained virological response to interferon-alpha is associated with improved outcome in HCV-related cirrhosis: a retrospective study. Hepatology 2007; 45: 579-587[PMID: 17326216 DOI: 10.1002/hep.21492]
52. Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, Inoue O, Yano M, Tanaka M, Fujiyama S, Nishiguchi S, Kuroki T, Imazeki F, Yokosuka O, Kinoyama S, Yamada G, Omata M. Interferon therapy reduces the risk for hepatocel-lular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med 1999; 131: 174-181[PMID: 10428733 DOI: 10.7326/0003-4819-131-3-199908030-00003]
53. Liaw YF. Impact of therapy on the outcome of chronic hepatitis B. Liver Int 2013; 33 Suppl 1: 111-115[PMID: 23286854 DOI: 10.1111/liv.12057]
54. Singal AK, Salameh H, Kuo YF, Fontana RJ. Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocel-lular carcinoma in chronic hepatitis B. Aliment Pharmacol Ther 2013; 38: 98-106[PMID: 23713520 DOI: 10.1111/apt.12344]
55. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295: 65-73[PMID: 16391218 DOI: 10.1001/jama.295.1.65]
56. Chen JD, Yang HI, Iloeje UH, You SL, Lu SN, Wang LY, Su J, Sun CA, Liaw YF, Chen CJ. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010; 138: 1747-1754[PMID: 20114048 DOI: 10.1053/j.gastro.2010.01.042]
57. Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002; 347: 168-174[PMID: 12124405 DOI: 10.1056/NEJMoa013215]
58. Liaw YF, Tai DI, Chu CM, Lin DY, Sheen IS, Chen TJ, Pao CC. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study. Gastroenterology 1986; 90: 263-267[PMID: 2416625]
59. Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008; 48: 335-352[PMID: 18096267 DOI: 10.1016/j.jhep.2007.11.011]
60. Sánchez-Tapias JM, Costa J, Mas A, Bruguera M, Rodés J. In-fuence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in western patients. Gastroenterology 2002; 123: 1848-1856[PMID: 12454842 DOI: 10.1053/gast.2002.37041]
61. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-699[PMID: 7560864 DOI: 10.1016/0168-8278(95)80226-6]
62. Lok AS, Seeff LB, Morgan TR, Di Bisceglie AM, Sterling RK, Curto TM, Everson GT, Lindsay KL, Lee WM, Bonkovsky HL, Dienstag JL, Ghany MG, Morishima C, Goodman ZD. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastro-enterology 2009; 136: 138-148[PMID: 18848939 DOI: 10.1053/ j.gastro.2008.09.014]
63. Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, Imamura J, Goto T, Kanai F, Kato N, Ikeda H, Shiina S, Kawabe T, Omata M. Prospective risk assessment for hepa-tocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology 2009; 49: 1954-1961[PMID: 19434742 DOI: 10.1002/hep.22870]
64. Ikeda K, Arase Y, Saitoh S, Kobayashi M, Someya T, Hosaka T, Akuta N, Suzuki Y, Suzuki F, Sezaki H, Kumada H, Tana-ka A, Harada H. Prediction model of hepatocarcinogenesis for patients with hepatitis C virus-related cirrhosis. Validation with internal and external cohorts. J Hepatol 2006; 44: 1089-1097[PMID: 16618514 DOI: 10.1016/j.jhep.2006.02.008]
65. Kurosaki M, Hiramatsu N, Sakamoto M, Suzuki Y, Iwasaki M, Tamori A, Matsuura K, Kakinuma S, Sugauchi F, Sakamoto N, Nakagawa M, Izumi N. Data mining model using simple and readily available factors could identify patients at high risk for hepatocellular carcinoma in chronic hepatitis C. J Hepatol 2012; 56: 602-608[PMID: 22027574 DOI: 10.1016/j.jhep.2011.09.011]
66. Zoli M, Magalotti D, Bianchi G, Gueli C, Marchesini G, Pisi E. Effcacy of a surveillance program for early detection of hepa-tocellular carcinoma. Cancer 1996; 78: 977-985[PMID: 8780534]
67. Sato T, Tateishi R, Yoshida H, Ohki T, Masuzaki R, Imamura J, Goto T, Kanai F, Obi S, Kato N, Shiina S, Kawabe T, Omata M. Ultrasound surveillance for early detection of hepatocellular carcinoma among patients with chronic hepatitis C. Hepatol Int 2009; 3: 544-550[PMID: 19669240 DOI: 10.1007/s12072-009-9145-y]
68. Bayati N, Silverman AL, Gordon SC. Serum alpha-fetopro-tein levels and liver histology in patients with chronic hepatitis C. Am J Gastroenterol 1998; 93: 2452-2456[PMID: 9860408 DOI: 10.1111/j.1572-0241.1998.00703.x]
69. Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, Rapaccini G, Del Poggio P, Di Nolfo MA, Benvegnù L, Zoli M, Borzio F, Bernardi M, Trevisani F. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither? Am J Gastroenterol 2006; 101: 524-532[PMID: 16542289 DOI: 10.1111/j.1572-0241.2006.00443.x]
70. Chen TM, Huang PT, Tsai MH, Lin LF, Liu CC, Ho KS, Siauw CP, Chao PL, Tung JN. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepa-tocellular carcinoma, and its normalization after pegylated interferon alfa 2a-ribavirin combination therapy. J Gastroenterol Hepatol 2007; 22: 669-675[PMID: 17444854 DOI: 10.1111/ j.1440-1746.2007.04898.x]
71. Di Bisceglie AM, Sterling RK, Chung RT, Everhart JE, Dien-stag JL, Bonkovsky HL, Wright EC, Everson GT, Lindsay KL, Lok AS, Lee WM, Morgan TR, Ghany MG, Gretch DR. Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C Trial. J Hepatol 2005; 43: 434-441[PMID: 16136646]
72. Nomura F, Ohnishi K, Tanabe Y. Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients. Cancer 1989; 64: 1700-1707[PMID: 2477133]
73. Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: signif-cance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer 2004; 112: 44-50[PMID: 15305374 DOI: 10.1002/ijc.20279]
74. Di Bisceglie AM, Hoofnagle JH. Elevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B. Cancer 1989; 64: 2117-2120[PMID: 2478280]
75. Trevisani F, D'Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P, Domenicali M, De Notariis S, Roda E, Bernardi M. Serum alpha-fetoprotein for diagnosis of hepato-cellular carcinoma in patients with chronic liver disease: infu-ence of HBsAg and anti-HCV status. J Hepatol 2001; 34: 570-575[PMID: 11394657 DOI: 10.1016/S0168-8278(00)00053-2]
76. Andersson KL, Salomon JA, Goldie SJ, Chung RT. Cost effectiveness of alternative surveillance strategies for hepatocel-lular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol 2008; 6: 1418-1424[PMID: 18848905 DOI: 10.1016/ j.cgh.2008.08.005]
77. Sherman M. Alphafetoprotein: an obituary. J Hepatol 2001; 34: 603-605[PMID: 11394662 DOI: 10.1016/S0168-8278(01)00025-3]
78. Sherman M. Serological surveillance for hepatocellular carcinoma: time to quit. J Hepatol 2010; 52: 614-615[PMID: 20185193 DOI: 10.1016/j.jhep.2009.11.026]
79. Giannini EG, Farinati F, Trevisani F. Alpha-fetoprotein in hepa-tocellular carcinoma surveillance: wake not the dead. Hepatology 2011; 54: 376-377[PMID: 21710475 DOI: 10.1002/hep.24196]
80. Giannini EG, Erroi V, Trevisani F. Effectiveness of α-fetoprotein for hepatocellular carcinoma surveillance: the return of the living-dead? Expert Rev Gastroenterol Hepatol 2012; 6: 441-444[PMID: 22928896 DOI: 10.1586/egh.12.30]
81. Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, Van Cutsem E, Singh H, Chow WC, Ooi LL, Chow P, Khin MW, Koo WH. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 2009; 10: 1111-1118[PMID: 19880065 DOI: 10.1016/S1470-2045(09)70241-4]
82. Saab S, Ly D, Nieto J, Kanwal F, Lu D, Raman S, Amado R, Nuesse B, Durazo F, Han S, Farmer DG, Ghobrial RM, Yersiz H, Chen P, Schwegel K, Goldstein LI, Tong M, Busuttil RW. He-patocellular carcinoma screening in patients waiting for liver transplantation: a decision analytic model. Liver Transpl 2003; 9: 672-681[PMID: 12827551 DOI: 10.1053/jlts.2003.50120]
83. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-699[PMID: 8594428 DOI: 10.1056/NEJM199603143341104]
84. Northup PG, Berg CL. Hepatocellular carcinoma and model for end-stage liver disease exceptions: the more we understand, the more challenging the allocation gets. Liver Transpl 2012; 18: 381-383[PMID: 22323420 DOI: 10.1002/lt.23409]
85. Vitale A, Volk ML, Gambato M, Zanus G, D'Amico F, Car-raro A, Pauletto A, Bonsignore P, Scopelliti M, Polacco M, Russo F, Senzolo M, Burra P, Romano A, Angeli P, Cillo U. Estimation of the harm to the waiting list as a crucial factor in the selection of patients with hepatocellular carcinoma for liver transplantation. Transplant Proc 2010; 42: 1194-1196[PMID: 20534259 DOI: 10.1016/j.transproceed.2010.03.089]
86. Kim CK, Lim JH, Lee WJ. Detection of hepatocellular carcinomas and dysplastic nodules in cirrhotic liver: accuracy of ultrasonography in transplant patients. J Ultrasound Med 2001; 20: 99-104[PMID: 11211142]
87. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 2002; 36: 1349-1354[PMID: 12447858]
88. Giannini EG, Marabotto E, Savarino V, Trevisani F, Di Nolfo MA, Del Poggio P, Benvegnù L, Farinati F, Zoli M, Borzio F, Caturelli E, Chiaramonte M. Hepatocellular carcinoma in patients with cryptogenic cirrhosis. Clin Gastroenterol Hepatol 2009; 7: 580-585[PMID: 19418607 DOI: 10.1016/j.cgh.2009.01.001]
89. Santi V, Buccione D, Di Micoli A, Fatti G, Frigerio M, Farinati F, Del Poggio P, Rapaccini G, Di Nolfo MA, Benvegnù L, Zoli M, Borzio F, Giannini EG, Caturelli E, Chiaramonte M, Bernardi M, Trevisani F. The changing scenario of hepatocellular carcinoma over the last two decades in Italy. J Hepatol 2012; 56: 397-405[PMID: 21756850 DOI: 10.1016/j.jhep.2011.05.026]
90. Singal AG, Conjeevaram HS, Volk ML, Fu S, Fontana RJ, Askari F, Su GL, Lok AS, Marrero JA. Effectiveness of hepa-tocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev 2012; 21: 793-799[PMID: 22374994 DOI: 10.1158/1055-9965]
91. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011; 34: 274-285[PMID: 21623852 DOI: 10.1111/j.1365-2036.2011.04724.x]
92. Barbara L, Benzi G, Gaiani S, Fusconi F, Zironi G, Siringo S, Rigamonti A, Barbara C, Grigioni W, Mazziotti A. Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology 1992; 16: 132-137[PMID: 1352268]
93. Han KH, Kim do Y, Park JY, Ahn SH, Kim J, Kim SU, Kim JK, Lee KS, Chon CY. Survival of hepatocellular carcinoma patients may be improved in surveillance interval not more than 6 mo compared with more than 6 mo: a 15-year prospective study. J Clin Gastroenterol 2013; 47: 538-544[PMID: 23340065 DOI: 10.1097/MCG.0b013e3182755c13]
94. Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, Roulot D, Mallat A, Hillaire S, Cales P, Ollivier I, Vinel JP, Mathurin P, Bronowicki JP, Vilgrain V, N'Kontchou G, Beau-grand M, Chevret S. Ultrasonographic surveillance of hepatocel-lular carcinoma in cirrhosis: a randomized trial comparing 3-and 6-mo periodicities. Hepatology 2011; 54: 1987-1997[PMID: 22144108 DOI: 10.1002/hep.24545]
95. Nouso K, Tanaka H, Uematsu S, Shiraga K, Okamoto R, On-ishi H, Nakamura S, Kobayashi Y, Araki Y, Aoki N, Shiratori Y. Cost-effectiveness of the surveillance program of hepato-cellular carcinoma depends on the medical circumstances. J Gastroenterol Hepatol 2008; 23: 437-444[PMID: 17683496 DOI: 10.1111/j.1440-1746.2007.05054.x]
96. Cucchetti A, Trevisani F, Cescon M, Ercolani G, Farinati F, Poggio PD, Rapaccini G, Nolfo MA, Benvegnù L, Zoli M, Borzio F, Giannini EG, Caturelli E, Chiaramonte M, Pinna AD. Cost-effectiveness of semi-annual surveillance for hepa-tocellular carcinoma in cirrhotic patients of the Italian Liver Cancer population. J Hepatol 2012; 56: 1089-1096[PMID: 22245900 DOI: 10.1016/j.jhep.2011.11.022]
97. Thompson Coon J, Rogers G, Hewson P, Wright D, Anderson R, Jackson S, Ryder S, Cramp M, Stein K. Surveillance of cirrhosis for hepatocellular carcinoma: a cost-utility analysis. Br J Cancer 2008; 98: 1166-1175[PMID: 18382459 DOI: 10.1038/ sj.bjc.6604301]
98. Qian MY, Yuwei J R, Angus P, Schelleman T, Johnson L, Gow P. Efficacy and cost of a hepatocellular carcinoma screening program at an Australian teaching hospital. J Gastroenterol Hepatol 2010; 25: 951-956[PMID: 20546449 DOI: 10.1111/ j.1440-1746.2009.06203.x]
99. Patel D, Terrault NA, Yao FY, Bass NM, Ladabaum U. Cost-effectiveness of hepatocellular carcinoma surveillance in patients with hepatitis C virus-related cirrhosis. Clin Gastroenterol Hepatol 2005; 3: 75-84[PMID: 15645408 DOI: 10.1016/S1542-3565(04)00443-4]
100. Arguedas MR, Chen VK, Eloubeidi MA, Fallon MB. Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis. Am J Gastroenterol 2003; 98: 679-690[PMID: 12650806]
101. Tanaka H, Iijima H, Nouso K, Aoki N, Iwai T, Takashima T, Sakai Y, Aizawa N, Iwata K, Ikeda N, Iwata Y, Enomoto H, Saito M, Imanishi H, Nishiguchi S. Cost-effectiveness analysis on the surveillance for hepatocellular carcinoma in liver cirrhosis patients using contrast-enhanced ultrasonography. Hepatol Res 2012; 42: 376-384[PMID: 22221694 DOI: 10.1111/ j.1872-034X.2011.00936.x]
102. Cucchetti A, Piscaglia F, Cescon M, Colecchia A, Ercolani G, Bolondi L, Pinna AD. Cost-effectiveness of hepatic resection versus percutaneous radiofrequency ablation for early hepatocellular carcinoma. J Hepatol 2013; 59: 300-307[PMID: 23603669 DOI: 10.1016/j.jhep.2013.04.009]
103. Roskams T. Anatomic pathology of hepatocellular carcinoma: impact on prognosis and response to therapy. Clin Liver Dis 2011; 15: 245-259, vii-x[PMID: 21689611 DOI: 10.1016/ j.cld.2011.03.004]
104. Italian Association for the Study of the Liver (AISF); AISF Expert Panel; AISF Coordinating Committee; Bolondi L, Cillo U, Colombo M, Craxì A, Farinati F, Giannini EG, Golferi R, Levrero M, Pinna AD, Piscaglia F, Raimondo G, Trevisani F, Bruno R, Caraceni P, Ciancio A, Coco B, Fraquelli M, Ren-dina M, Squadrito G, Toniutto P. Position paper of the Italian Association for the Study of the Liver (AISF): the multidis-ciplinary clinical approach to hepatocellular carcinoma. Dig Liver Dis 2013; 45: 712-723[PMID: 23769756 DOI: 10.1016/ j.dld.2013.01.012]
105. Bolondi L, Gaiani S, Benzi G, Zironi G, Rigamonti A, Fus-coni F, Barbara L. Ultrasonography and guided biopsy in the diagnosis of hepatocellular carcinoma. Ital J Gastroenterol 1992; 24: 46-49[PMID: 1315177]
106. Trevisani F, Cantarini MC, Wands JR, Bernardi M. Recent advances in the natural history of hepatocellular carcinoma. Carcinogenesis 2008; 29: 1299-1305[PMID: 18515282 DOI: 10.1093/carcin/bgn113]
107. Colli A, Fraquelli M, Casazza G, Massironi S, Colucci A, Conte D, Duca P. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol 2006; 101: 513-523[PMID: 16542288 DOI: 10.1111/j.1572-0241.2006.00467. x]
108. Lencioni R. Surveillance and early diagnosis of hepatocel-lular carcinoma. Dig Liver Dis 2010; 42 Suppl 3: S223-S227[PMID: 20547307 DOI: 10.1016/S1590-8658(10)60509-9]
109. Bolondi L, Gaiani S, Celli N, Golferi R, Grigioni WF, Leoni S, Venturi AM, Piscaglia F. Characterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology 2005; 42: 27-34[PMID: 15954118 DOI: 10.1002/hep.20728]
110. Golferi R, Renzulli M, Lucidi V, Corcioni B, Trevisani F, Bolon-di L. Contribution of the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI to Dynamic MRI in the detection of hypovascular small (≤ 2 cm) HCC in cirrhosis. Eur Radiol 2011; 21: 1233-1242[PMID: 21293864 DOI: 10.1007/s00330-010-2030-1]
111. Nakashima Y, Nakashima O, Hsia CC, Kojiro M, Tabor E. Vas-cularization of small hepatocellular carcinomas: correlation with differentiation. Liver 1999; 19: 12-18[PMID: 9928760]
112. Kojiro M, Roskams T. Early hepatocellular carcinoma and dysplastic nodules. Semin Liver Dis 2005; 25: 133-142[PMID: 15918142 DOI: 10.1055/s-2005-871193]
113. Vilana R, Forner A, Bianchi L, García-Criado A, Rimola J, de Lope CR, Reig M, Ayuso C, Brú C, Bruix J. Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound. Hepatology 2010; 51: 2020-2029[PMID: 20512990 DOI: 10.1002/hep.23600]
114. Barreiros AP, Piscaglia F, Dietrich CF. Contrast enhanced ultrasound for the diagnosis of hepatocellular carcinoma (HCC): comments on AASLD guidelines. J Hepatol 2012; 57: 930-932[PMID: 22739095 DOI: 10.1016/j.jhep.2012.04.018]
115. Galassi M, Iavarone M, Rossi S, Bota S, Vavassori S, Rosa L, Leoni S, Venerandi L, Marinelli S, Sangiovanni A, Veronese L, Fraquelli M, Granito A, Golferi R, Colombo M, Bolondi L, Piscaglia F. Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound. Liver Int 2013; 33: 771-779[PMID: 23445369 DOI: 10.1111/liv.12124]
116. Sersté T, Barrau V, Ozenne V, Vullierme MP, Bedossa P, Farges O, Valla DC, Vilgrain V, Paradis V, Degos F. Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: role of biopsy. Hepatology 2012; 55: 800-806[PMID: 22006503 DOI: 10.1002/hep.24746]
117. Davila JA, Weston A, Smalley W, El-Serag HB. Utilization of screening for hepatocellular carcinoma in the United States. J Clin Gastroenterol 2007; 41: 777-782[PMID: 17700427 DOI: 10.1097/MCG.0b013e3180381560]
118. Davila JA, Henderson L, Kramer JR, Kanwal F, Richardson PA, Duan Z, El-Serag HB. Utilization of surveillance for hepa-tocellular carcinoma among hepatitis C virus-infected veterans in the United States. Ann Intern Med 2011; 154: 85-93[PMID: 21242365 DOI: 10.7326/0003-4819-154-2-201101180-00006]
119. Davila JA, Kramer JR, Duan Z, Richardson PA, Tyson GL, Sada YH, Kanwal F, El-Serag HB. Referral and receipt of treatment for hepatocellular carcinoma in United States veterans: effect of patient and nonpatient factors. Hepatology 2013; 57: 1858-1868[PMID: 23359313 DOI: 10.1002/hep.26287]
120. El-Serag HB, Alsarraj A, Richardson P, Davila JA, Kramer JR, Durfee J, Kanwal F. Hepatocellular carcinoma screening practices in the Department of Veterans Affairs: findings from a national facility survey. Dig Dis Sci 2013; 58: 3117-3126[PMID: 23868438 DOI: 10.1007/s10620-013-2794-7]
121. Chalasani N, Said A, Ness R, Hoen H, Lumeng L. Screening for hepatocellular carcinoma in patients with cirrhosis in the United States: results of a national survey. Am J Gastro-enterol 1999; 94: 2224-2229[PMID: 10445554 DOI: 10.1111/ j.1572-0241.1999.01297.x]
122. Kennedy NA, Rodgers A, Altus R, McCormick R, Wundke R, Wigg AJ. Optimisation of hepatocellular carcinoma surveillance in patients with viral hepatitis: a quality improvement study. Intern Med J 2013; 43: 772-777[PMID: 23611607 DOI: 10.1111/ imj.12166]