Advertisement

Current Hepatology Reports

, Volume 16, Issue 1, pp 64–71 | Cite as

Tailored Algorithms for Hepatocellular Carcinoma Surveillance: Is One-Size-Fits-All Strategy Outdated?

  • Nicolas Goossens
  • C. Billie Bian
  • Yujin Hoshida
Hepatic Cancer (A Singal and A Mufti, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Hepatic Cancer

Abstract

Purpose of Review

Current clinical practice guidelines recommend regular hepatocellular carcinoma (HCC) surveillance with biannual ultrasound with or without serum alpha-fetoprotein uniformly applied to all patients with cirrhosis. However, clinical implementation of this one-size-fits-all strategy has been challenging as evidenced by very low application rate below 20% due to various reasons, including suboptimal performance of the surveillance modalities.

Recent Findings

Newly emerging imaging techniques such as abbreviated MRI (AMRI) and molecular HCC risk biomarkers have increasingly become available for clinical evaluation and implementation. These technologies may have a potential to reshape HCC surveillance by enabling tailored strategies. This would involve performing optimized surveillance tests according to individual HCC risk and allocating limited medical resources for HCC surveillance based on cost-effectiveness.

Summary

Tailored HCC surveillance could lead to achievement of precision HCC care and substantial improvement of the current dismal patient prognosis.

Keywords

Hepatocellular carcinoma Surveillance Precision medicine Molecular risk stratification 

Abbreviations

AFP

α-Fetoprotein

ALD

Alcoholic liver disease

CT

Computed tomography

HBV

Hepatitis B virus

HCC

Hepatocellular carcinoma

HCV

Hepatitis C virus

MRI

Magnetic resonance imaging

NAFLD

Non-alcoholic fatty liver disease

SNP

Single nucleotide polymorphism

Notes

Acknowledgements

This work was supported by the FLAGS foundation, the Nuovo-Soldati Cancer Research Foundation, and a research fellowship by the Geneva University Hospital to NG and NIH/NIDDK R01 DK099558, Irma T. Hirschl Trust, Dr. Harold and Golden Lamport Research Award, European Union ERC-2014-AdG-671231-HEPCIR, and US Department of Defense W81XWH-16-1-0363 to YH.

Compliance with Ethical Standards

Conflict of Interest

Nicolas Goossens, C. Billie Bian, and Yujin Hoshida each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262.CrossRefPubMedGoogle Scholar
  2. 2.
    Singal AG, El-Serag HB. Hepatocellular carcinoma from epidemiology to prevention: translating knowledge into practice. Clin Gastroenterol Hepatol. 2015;13(12):2140–51. doi: 10.1016/j.cgh.2015.08.014.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Harris RJ, Thomas B, Griffiths J, Costella A, Chapman R, Ramsay M, et al. Increased uptake and new therapies are needed to avert rising hepatitis C-related end stage liver disease in England: modelling the predicted impact of treatment under different scenarios. J Hepatol. 2014;61(3):530–7. doi: 10.1016/j.jhep.2014.05.008.CrossRefPubMedGoogle Scholar
  4. 4.
    •• Singal AG, Pillai A, Tiro J. Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med. 2014;11(4):e1001624. doi: 10.1371/journal.pmed.1001624. A systematic review clarifying the benefit of HCC surveillance.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mittal S, Kanwal F, Ying J, Chung R, Sada YH, Temple S, et al. Effectiveness of surveillance for hepatocellular carcinoma in clinical practice: a United States cohort. J Hepatol. 2016;65(6):1148–54. doi: 10.1016/j.jhep.2016.07.025.CrossRefPubMedGoogle Scholar
  6. 6.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2. doi: 10.1002/hep.24199.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    EASL-EORTC. Clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43. doi: 10.1016/j.jhep.2011.12.001.CrossRefGoogle Scholar
  8. 8.
    Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, et al. Asian Pacific association for the study of the liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4(2):439–74. doi: 10.1007/s12072-010-9165-7.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kansagara D, Papak J, Pasha AS, O’Neil M, Freeman M, Relevo R, et al. Screening for hepatocellular carcinoma in chronic liver disease: a systematic review. Ann Intern Med. 2014;161(4):261–9. doi: 10.7326/M14-0558.CrossRefPubMedGoogle Scholar
  10. 10.
    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(6):1998–2004.CrossRefPubMedGoogle Scholar
  11. 11.
    Andersson KL, Salomon JA, Goldie SJ, Chung RT. Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2008;6(12):1418–24. doi: 10.1016/j.cgh.2008.08.005.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Singal AG, Nehra M, Adams-Huet B, Yopp AC, Tiro JA, Marrero JA, et al. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail? Am J Gastroenterol. 2013;108(3):425–32. doi: 10.1038/ajg.2012.449.CrossRefPubMedGoogle Scholar
  13. 13.
    Del Poggio P, Olmi S, Ciccarese F, Di Marco M, Rapaccini GL, Benvegnu L, et al. Factors that affect efficacy of ultrasound surveillance for early stage hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2014;12(11):1927–33. doi: 10.1016/j.cgh.2014.02.025. e2.CrossRefPubMedGoogle Scholar
  14. 14.
    Singal A, Volk ML, Waljee A, Salgia R, Higgins P, Rogers MA, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30(1):37–47. doi: 10.1111/j.1365-2036.2009.04014.x.CrossRefPubMedGoogle Scholar
  15. 15.
    Mourad A, Deuffic-Burban S, Ganne-Carrie N, Renaut-Vantroys T, Rosa I, Bouvier AM, et al. Hepatocellular carcinoma screening in patients with compensated hepatitis C virus (HCV)-related cirrhosis aware of their HCV status improves survival: a modeling approach. Hepatology. 2014;59(4):1471–81. doi: 10.1002/hep.26944.CrossRefPubMedGoogle Scholar
  16. 16.
    Singal AG, Conjeevaram HS, Volk ML, Fu S, Fontana RJ, Askari F, et al. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev. 2012;21(5):793–9. doi: 10.1158/1055-9965.EPI-11-1005.CrossRefPubMedGoogle Scholar
  17. 17.
    Song PP, Xia JF, Inagaki Y, Hasegawa K, Sakamoto Y, Kokudo N, et al. Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma. World J Gastroenterol. 2016;22(1):262–74. doi: 10.3748/wjg.v22.i1.262.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Gupta S, Bent S, Kohlwes J. Test characteristics of α-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C: a systematic review and critical analysis. Ann Intern Med. 2003;139(1):46–50.CrossRefPubMedGoogle Scholar
  19. 19.
    Mancebo A, González–Diéguez ML, Cadahía V, Varela M, Pérez R, Navascués CA, et al. Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups. Clin Gastroenterol Hepatol. 2013;11(1):95–101. doi: 10.1016/j.cgh.2012.09.007.CrossRefPubMedGoogle Scholar
  20. 20.
    Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):S35–50.CrossRefPubMedGoogle Scholar
  21. 21.
    El-Serag HB, Kanwal F. Epidemiology of hepatocellular carcinoma in the United States: where are we? where do we go? Hepatology. 2014;60(5):1767–75. doi: 10.1002/hep.27222.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    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(1):132–41. doi: 10.1002/hep.23615.CrossRefPubMedGoogle Scholar
  23. 23.
    Singal AG, Yopp A, Skinner CS, Packer M, Lee WM, Tiro JA. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review. J Gen Intern Med. 2012;27(7):861–7.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Edenvik P, Davidsdottir L, Oksanen A, Isaksson B, Hultcrantz R, Stål P. Application of hepatocellular carcinoma surveillance in a European setting. What can we learn from clinical practice? Liver Int. 2015;35(7):1862–71.CrossRefPubMedGoogle Scholar
  25. 25.
    Hirata A, Hirata T, Takahashi Y, Nakayama T. Surveillance rates for hepatocellular carcinoma among patients with cirrhosis, chronic hepatitis B, and chronic hepatitis C based on Japanese claims database. Hepatology Research. 2016Google Scholar
  26. 26.
    Singal AG, Yopp AC, Gupta S, Skinner CS, Halm EA, Okolo E, et al. Failure rates in the hepatocellular carcinoma surveillance process. Cancer Prev Res. 2012;5(9):1124–30. doi: 10.1158/1940-6207.CAPR-12-0046.CrossRefGoogle Scholar
  27. 27.
    Dalton-Fitzgerald E, Tiro J, Kandunoori P, Halm EA, Yopp A, Singal AG, et al. Practice patterns and attitudes of primary care providers and barriers to surveillance of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13:791–8. e1.CrossRefPubMedGoogle Scholar
  28. 28.
    • Singal AG, Tiro JA, Marrero JA, McCallister K, Mejias C, Adamson B et al. Mailed outreach program increases ultrasound screening of patients with cirrhosis for hepatocellular carcinoma. Gastroenterology. 2016. A practical outreach program showing a doubling of HCC screening rates with a simple intervention Google Scholar
  29. 29.
    Simmons O, Fetzer D, Yokoo T, Marrero J, Yopp A, Kono Y, et al. Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis. Aliment Pharmacol Ther. 2017;45(1):169–77.CrossRefPubMedGoogle Scholar
  30. 30.
    Yu NC, Chaudhari V, Raman SS, Lassman C, Tong MJ, Busuttil RW, et al. CT and MRI improve detection of hepatocellular carcinoma, compared with ultrasound alone, in patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9(2):161–7. doi: 10.1016/j.cgh.2010.09.017.CrossRefPubMedGoogle Scholar
  31. 31.
    Pocha C, Dieperink E, McMaken K, Knott A, Thuras P, Ho S. Surveillance for hepatocellular cancer with ultrasonography vs. computed tomography—a randomised study. Aliment Pharmacol Ther. 2013;38(3):303–12.CrossRefPubMedGoogle Scholar
  32. 32.
    • Kim SY, An J, Lim Y-S, Han S, Lee J-Y, Byun JH et al. MRI with liver-specific contrast for surveillance of patients with cirrhosis at high risk of hepatocellular carcinoma. JAMA Oncology. 2016. A prospective study comparing ultrasound to MRI-based HCC surveillance Google Scholar
  33. 33.
    • Marks RM, Ryan A, Heba ER, Tang A, Wolfson TJ, Gamst AC et al. Diagnostic per-patient accuracy of an abbreviated hepatobiliary phase gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance. American Journal of Roentgenology. 2015;204(3):527–35. Proof of principle of effectiveness of an abbreviated MRI protocol for HCC surveillance Google Scholar
  34. 34.
    Besa C, Lewis S, Pandharipande PV, Chhatwal J, Kamath A, Cooper N et al. Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted imaging at the delayed phase post gadoxetic acid. Abdominal Radiology. 2016:1–12Google Scholar
  35. 35.
    Goossens N, Hoshida Y. Is hepatocellular cancer the same disease in alcoholic and non-alcoholic fatty liver diseases? Gastroenterology. 2016. doi: 10.1053/j.gastro.2016.01.006.Google Scholar
  36. 36.
    Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65(4):719–26.CrossRefPubMedGoogle Scholar
  37. 37.
    Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65(4):727–33.CrossRefPubMedGoogle Scholar
  38. 38.
    El‐Serag HB, Kanwal F, Richardson P, Kramer J. Risk of hepatocellular carcinoma after sustained virologic response in veterans with HCV‐infection. Hepatology. 2016Google Scholar
  39. 39.
    Baumert TF, Jühling F, Atsushi O, Hoshida Y. Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals. BMC Med. 2017 (in press).Google Scholar
  40. 40.
    Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi‐Society Task Force on Colorectal Cancer, and the American College of Radiology*†. CA Cancer J Clin. 2008;58(3):130–60.CrossRefPubMedGoogle Scholar
  41. 41.
    Tice JA, Cummings SR, Smith-Bindman R, Ichikawa L, Barlow WE, Kerlikowske K. Using clinical factors and mammographic breast density to estimate breast cancer risk: development and validation of a new predictive model. Ann Intern Med. 2008;148(5):337–47.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Parmigiani G, Chen S, Iversen ES, Friebel TM, Finkelstein DM, Anton-Culver H, et al. Validity of models for predicting BRCA1 and BRCA2 mutations. Ann Intern Med. 2007;147(7):441–50.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Goossens N, Nakagawa S, Hoshida Y. Molecular prognostic prediction in liver cirrhosis. World J Gastroenterol. 2015;21(36):10262–73. doi: 10.3748/wjg.v21.i36.10262.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Tanabe KK, Lemoine A, Finkelstein DM, Kawasaki H, Fujii T, Chung RT, et al. Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA. 2008;299(1):53–60. doi: 10.1001/jama.2007.65.CrossRefPubMedGoogle Scholar
  45. 45.
    Abu Dayyeh BK, Yang M, Fuchs BC, Karl DL, Yamada S, Sninsky JJ, et al. A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma. Gastroenterology. 2011;141(1):141–9. doi: 10.1053/j.gastro.2011.03.045.CrossRefPubMedGoogle Scholar
  46. 46.
    Nahon P, Sutton A, Rufat P, Charnaux N, Mansouri A, Moreau R, et al. A variant in myeloperoxidase promoter hastens the emergence of hepatocellular carcinoma in patients with HCV-related cirrhosis. J Hepatol. 2012;56(2):426–32. doi: 10.1016/j.jhep.2011.08.010.CrossRefPubMedGoogle Scholar
  47. 47.
    Hoshida Y, Villanueva A, Sangiovanni A, Sole M, Hur C, Andersson KL, et al. Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis. Gastroenterology. 2013;144(5):1024–30. doi: 10.1053/j.gastro.2013.01.021.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    • King LY, Canasto-Chibuque C, Johnson KB, Yip S, Chen X, Kojima K, et al. A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration. Gut. 2014. doi: 10.1136/gutjnl-2014-307862. Molecular risk stratification of patients with early stage cirrhosis using a gene expression molecular score.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Hoshida Y, Villanueva A, Kobayashi M, Peix J, Chiang DY, Camargo A, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med. 2008;359(19):1995–2004. doi: 10.1056/NEJMoa0804525.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Nakagawa S, Wei L, Song W, Higashi T, Ghoshal S, Kim RS et al. Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition. Cancer Cell. 2016, in press.Google Scholar
  51. 51.
    Furlan A, Marin D, Agnello F, Di Martino M, Di Marco V, Lagalla R, et al. Hepatocellular carcinoma presenting at contrast-enhanced multi-detector-row computed tomography or gadolinium-enhanced magnetic resonance Imaging as a small (≤2 cm), indeterminate nodule: growth rate and optimal interval time for imaging follow-up. J Comput Assist Tomogr. 2012;36(1):20–5.CrossRefPubMedGoogle Scholar
  52. 52.
    Taouli B, Goh JS, Lu Y, Qayyum A, Yeh BM, Merriman RB, et al. Growth rate of hepatocellular carcinoma: evaluation with serial computed tomography or magnetic resonance imaging. J Comput Assist Tomogr. 2005;29(4):425–9.CrossRefPubMedGoogle Scholar
  53. 53.
    Santi V, Trevisani F, Gramenzi A, Grignaschi A, Mirici-Cappa F, Del Poggio P, et al. Semiannual surveillance is superior to annual surveillance for the detection of early hepatocellular carcinoma and patient survival. J Hepatol. 2010;53(2):291–7.CrossRefPubMedGoogle Scholar
  54. 54.
    Trinchet JC, Chaffaut C, Bourcier V, Degos F, Henrion J, Fontaine H, et al. Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis: a randomized trial comparing 3- and 6-month periodicities. Hepatology. 2011;54(6):1987–97. doi: 10.1002/hep.24545.CrossRefPubMedGoogle Scholar
  55. 55.
    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(4):422–34.CrossRefPubMedGoogle Scholar
  56. 56.
    Lin OS, Keeffe EB, Sanders GD, Owens DK. Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C. Aliment Pharmacol Ther. 2004;19(11):1159–72. doi: 10.1111/j.1365-2036.2004.01963.x.CrossRefPubMedGoogle Scholar
  57. 57.
    Goossens N, Singal AG, King LY, Andersson KL, Fuchs BC, Besa C et al., editors. Cost-effectiveness of a risk-stratified hepatocellular carcinoma surveillance strategy in patients with cirrhosis. HEPATOLOGY; 2016: WILEY-BLACKWELL 111 RIVER ST, HOBOKEN 07030–5774, NJ USAGoogle Scholar
  58. 58.
    Yoshihiroshimauchi M, Ryokokuromatsu RO, Yukiotateishi S, ONO N, Yutani S, Hiroakinagamatsu S, et al. A simultaneous monitoring of Lens culinaris agglutinin a-reactive a-fetoprotein and des-γ-carboxy prothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients. Oncol Rep. 2000;7:249–56.Google Scholar
  59. 59.
    Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. Cancer Biomark. 2007;3(2):79–87.CrossRefPubMedGoogle Scholar
  60. 60.
    Sterling RK, Jeffers L, Gordon F, Sherman M, Venook AP, Reddy KR, et al. Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis. Am J Gastroenterol. 2007;102(10):2196–205.CrossRefPubMedGoogle Scholar
  61. 61.
    Lok AS, Sterling RK, Everhart JE, Wright EC, Hoefs JC, Di Bisceglie AM, et al. Des-γ-carboxy prothrombin and α-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology. 2010;138(2):493–502.CrossRefPubMedGoogle Scholar
  62. 62.
    Wang M, Long RE, Comunale MA, Junaidi O, Marrero J, Di Bisceglie AM, et al. Novel fucosylated biomarkers for the early detection of hepatocellular carcinoma. Cancer Epidemiol Biomark Prev. 2009;18(6):1914–21.CrossRefGoogle Scholar
  63. 63.
    Marrero JA, Romano PR, Nikolaeva O, Steel L, Mehta A, Fimmel CJ, et al. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. J Hepatol. 2005;43(6):1007–12.CrossRefPubMedGoogle Scholar
  64. 64.
    Tian L, Wang Y, Xu D, Gui J, Jia X, Tong H, et al. Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases. Int J Cancer. 2011;129(8):1923–31.CrossRefPubMedGoogle Scholar
  65. 65.
    Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, Sangrajrang S, et al. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology. 2012;55(2):483–90. doi: 10.1002/hep.24703.CrossRefPubMedGoogle Scholar
  66. 66.
    Duarte-Salles T, Misra S, Stepien M, Plymoth A, Muller D, Overvad K, et al. Circulating osteopontin and prediction of hepatocellular carcinoma development in a large European population. Cancer Prev Res (Phila). 2016;9(9):758–65. doi: 10.1158/1940-6207.CAPR-15-0434.CrossRefGoogle Scholar
  67. 67.
    Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, et al. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res. 2004;64(7):2418–23.CrossRefPubMedGoogle Scholar
  68. 68.
    Beneduce L, Castaldi F, Marino M, Quarta S, Ruvoletto M, Benvegnu L, et al. Squamous cell carcinoma antigen-immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma. Cancer. 2005;103(12):2558–65. doi: 10.1002/cncr.21106.CrossRefPubMedGoogle Scholar
  69. 69.
    Shen Q, Fan J, Yang XR, Tan Y, Zhao W, Xu Y, et al. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol. 2012;13(8):817–26. doi: 10.1016/S1470-2045(12)70233-4.CrossRefPubMedGoogle Scholar
  70. 70.
    Z-q Z, Meng H, Wang N, Liang LN, Liu LN, Lu SM, et al. Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma. Diagn Pathol. 2014;9(1):1.CrossRefGoogle Scholar
  71. 71.
    Lin X-J, Chong Y, Guo Z-W, Xie C, Yang X-J, Zhang Q, et al. A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study. Lancet Oncol. 2015;16(7):804–15.CrossRefPubMedGoogle Scholar
  72. 72.
    Liu XE, Desmyter L, Gao CF, Laroy W, Dewaele S, Vanhooren V, et al. N-glycomic changes in hepatocellular carcinoma patients with liver cirrhosis induced by hepatitis B virus. Hepatology. 2007;46(5):1426–35. doi: 10.1002/hep.21855.CrossRefPubMedGoogle Scholar
  73. 73.
    Biselli M, Conti F, Gramenzi A, Frigerio M, Cucchetti A, Fatti G, et al. A new approach to the use of α-fetoprotein as surveillance test for hepatocellular carcinoma in patients with cirrhosis. Br J Cancer. 2015;112(1):69–76.CrossRefPubMedGoogle Scholar
  74. 74.
    El-Serag HB, Kanwal F, Davila JA, Kramer J, Richardson P, 5. A new laboratory-based algorithm to predict development of hepatocellular carcinoma in patients with hepatitis C and cirrhosis. Gastroenterology. 2014;146:1249–55. doi: 10.1053/j.gastro.2014.01.045. e1.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Hung Y-C, Lin C-L, Liu C-J, Hung H, Lin S-M, Lee S-D, et al. Development of risk scoring system for stratifying population for hepatocellular-carcinoma screening. Hepatology. 2015;61:1934–44. doi: 10.1002/hep.27610.CrossRefPubMedGoogle Scholar
  76. 76.
    Flemming JA, Yang JD, Vittinghoff E, Kim WR, Terrault NA. Risk prediction of hepatocellular carcinoma in patients with cirrhosis: the ADRESS-HCC risk model. Cancer. 2014;120(22):3485–93. doi: 10.1002/cncr.28832.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Velázquez RF, Rodríguez M, Navascués CA, Linares A, Pérez R, Sotorríos NG, et al. Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology. 2003;37(3):520–7. doi: 10.1053/jhep.2003.50093.CrossRefPubMedGoogle Scholar
  78. 78.
    Singal AG, Mukherjee A, Joseph Elmunzer B, Higgins PDR, Lok AS, Zhu J, et al. Machine learning algorithms outperform conventional regression models in predicting development of hepatocellular carcinoma. Am J Gastroenterol. 2013;108(11):1723–30. doi: 10.1038/ajg.2013.332.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Yuen M-F, Tanaka Y, Fong DY-T, Fung J, Wong DK-H, Yuen JC-H, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;50:80–8. doi: 10.1016/j.jhep.2008.07.023.CrossRefPubMedGoogle Scholar
  80. 80.
    Wong VW-S, Chan SL, Mo F, Chan T-C, Loong HH-F, Wong GL-H, et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. J Clin Oncol. 2010;28(10):1660–5. doi: 10.1200/jco.2009.26.2675.CrossRefPubMedGoogle Scholar
  81. 81.
    Wong GLH, Chan HLY, Wong CKY, Leung C, Chan CY, Ho PPL, et al. Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol. 2014;60(2):339–45. doi: 10.1016/j.jhep.2013.09.029.CrossRefPubMedGoogle Scholar
  82. 82.
    Yang HI, Yuen MF, Chan HLY, Han KH, Chen PJ, Kim DY, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol. 2011;12(6):568–74. doi: 10.1016/S1470-2045(11)70077-8.CrossRefPubMedGoogle Scholar
  83. 83.
    Ikeda M, Fujiyama S, Tanaka M, Sata M, Ide T, Yatsuhashi H, et al. Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon. J Gastroenterol. 2005;40(2):148–56. doi: 10.1007/s00535-004-1519-2.CrossRefPubMedGoogle Scholar
  84. 84.
    Chang KC, Hung CH, Lu SN, Wang JH, Lee CM, Chen CH, et al. A novel predictive score for hepatocellular carcinoma development in patients with chronic hepatitis C after sustained response to pegylated interferon and ribavirin combination therapy. J Antimicrob Chemother. 2012;67(11):2766–72. doi: 10.1093/jac/dks269.CrossRefPubMedGoogle Scholar
  85. 85.
    Chang KC, Wu YY, Hung CH, Lu SN, Lee CM, Chiu KW, et al. Clinical-guide risk prediction of hepatocellular carcinoma development in chronic hepatitis C patients after interferon-based therapy. Br J Cancer. 2013;109(9):2481–8. doi: 10.1038/bjc.2013.564.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Lok AS, Seeff LB, Morgan TR, di Bisceglie AM, Sterling RK, Curto TM, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology. 2009;136(1):138–48. doi: 10.1053/j.gastro.2008.09.014.CrossRefPubMedGoogle Scholar
  87. 87.
    Lee MH, Lu SN, Yuan Y, Yang HI, Jen CL, You SL, et al. Development and validation of a clinical scoring system for predicting risk of HCC in asymptomatic individuals seropositive for anti-HCV antibodies. PLoS One. 2014;9(5), e94760. doi: 10.1371/journal.pone.0094760.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Shin SH, Kim SU, Park JY, Kim Do Y, Ahn SH, Han KH, et al. Liver stiffness-based model for prediction of hepatocellular carcinoma in chronic hepatitis B virus infection: comparison with histological fibrosis. Liver Int. 2015;35(3):1054–62. doi: 10.1111/liv.12621.CrossRefPubMedGoogle Scholar
  89. 89.
    Suh B, Park S, Shin DW, Yun JM, Yang H-K, Yu SJ, et al. High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers. Hepatology. 2015;61(4):1261–8. doi: 10.1002/hep.27654.CrossRefPubMedGoogle Scholar
  90. 90.
    Kim JH, Sohn BH, Lee HS, Kim SB, Yoo JE, Park YY, et al. Genomic predictors for recurrence patterns of hepatocellular carcinoma: model derivation and validation. PLoS Med. 2014;11(12), e1001770. doi: 10.1371/journal.pmed.1001770.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Ji J, Eggert T, Budhu A, Forgues M, Takai A, Dang H, et al. Hepatic stellate cell and monocyte interaction contributes to poor prognosis in hepatocellular carcinoma. Hepatology. 2015. doi: 10.1002/hep.27822.Google Scholar
  92. 92.
    Guyot E, Sutton A, Rufat P, Laguillier C, Mansouri A, Moreau R, et al. PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. J Hepatol. 2013;58(2):312–8. doi: 10.1016/j.jhep.2012.09.036.CrossRefPubMedGoogle Scholar
  93. 93.
    Nahon P, Sutton A, Rufat P, Ziol M, Thabut G, Schischmanoff PO, et al. Liver iron, HFE gene mutations, and hepatocellular carcinoma occurrence in patients with cirrhosis. Gastroenterology. 2008;134(1):102–10. doi: 10.1053/j.gastro.2007.10.038.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Nicolas Goossens
    • 1
    • 2
  • C. Billie Bian
    • 1
  • Yujin Hoshida
    • 1
  1. 1.Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Graduate School of Biomedical SciencesIcahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Division of Gastroenterology and HepatologyGeneva University HospitalGenevaSwitzerland

Personalised recommendations