Skip to main content

Advertisement

SpringerLink
Log in

Assessment of HCC Risk in Patients with Chronic HBV (REACH, PAGE-B, and Beyond)

  • Hepatitis B (JK Lim, Section Editor)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To provide an updated overview on the current status of risk prediction scores for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus infection.

Recent Findings

More HCC risk scores have been developed, validated, and optimized (e.g., with liver stiffness measurement) in different patient and ethnic groups. Risk scores for treated patients with high negative predictive values would be able to identify patients who may not need HCC surveillance anymore as their HCC risk has been reduced by antiviral therapy.

Summary

Current HCC risk scores can accurately predict HCC in specific populations, in both treatment-naive patients and those receiving antiviral therapy. Different levels of care and different intensities of HCC surveillance should be offered according to the risk profile of patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CDARS:

Clinical Data Analysis and Reporting System

CHB:

Chronic hepatitis B

CI:

Confidence intervals

ETV:

Entecavir

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

ICD-9-CM:

International Classification of Diseases, Ninth Revision, Clinical Modification

IQR:

Interquartile range

LSM:

Liver stiffness measurement

NA:

Nucleos(t)ide analogues

TDF:

Tenofovir disoproxil fumarate

References

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

  1. Organization WH. Combating hepatitis B and C to reach elimination by 2030 - Advocacy brief. Website: http://www.who.int/hepatitis/publications/hep-elimination-by-2030-brief/en/. Accessed on 3 December 2019.

  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  3. • Polaris Observatory C. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. Lancet Gastroenterol Hepatol. 2018;3(6):383–403. https://doi.org/10.1016/S2468-1253(18)30056-6Chronic hepatitis B remains an important cause of liver cancer and death gloablly.

    Article  Google Scholar 

  4. Likhitsup A, Lok AS. Understanding the natural history of hepatitis B virus infection and the new definitions of cure and the endpoints of clinical trials. Clin Liver Dis. 2019;23(3):401–16. https://doi.org/10.1016/j.cld.2019.04.002.

    Article  PubMed  Google Scholar 

  5. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16(10):589–604. https://doi.org/10.1038/s41575-019-0186-y.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Yip TC, Lee HW, Wong VW, Wong GL, Tse YK, Lui GC, et al. Factors associated with improvement in MELD score after antiviral treatment in patients with chronic hepatitis B. J Gastroenterol Hepatol. 2020. https://doi.org/10.1111/jgh.15007.

  7. • Liu K, Choi J, Le A, Yip TC, Wong VW, Chan SL, et al. Tenofovir disoproxil fumarate reduces hepatocellular carcinoma, decompensation and death in chronic hepatitis B patients with cirrhosis. Aliment Pharmacol Ther. 2019;50(9):1037–48. https://doi.org/10.1111/apt.15499Potent antiviral therapy tenofovir disoproxil fumarate improves patient prognosis by reducing the risks of various complications.

    Article  CAS  PubMed  Google Scholar 

  8. Papatheodoridis GV, Idilman R, Dalekos GN, Buti M, Chi H, van Boemmel F, et al. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B. Hepatology. 2017;66(5):1444–53. https://doi.org/10.1002/hep.29320.

    Article  CAS  PubMed  Google Scholar 

  9. • Yip TC, Wong GL, Chan HL, Tse YK, Lam KL, Lui GC, et al. HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2019;70(3):361–70. https://doi.org/10.1016/j.jhep.2018.10.014Patients who are able to achieve functional cure of chronic hepatitis B would have further risk reduction of liver cancer and other cirrhotic complications.

    Article  CAS  PubMed  Google Scholar 

  10. Hsu YC, Ho HJ, Lee TY, Huang YT, Wu MS, Lin JT, et al. Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir. J Viral Hepat. 2018;25(5):543–51. https://doi.org/10.1111/jvh.12832.

    Article  CAS  PubMed  Google Scholar 

  11. Hsu YC, Yip TC, Ho HJ, Wong VW, Huang YT, El-Serag HB, et al. Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B. J Hepatol. 2018;69(2):278–85. https://doi.org/10.1016/j.jhep.2018.02.032.

    Article  PubMed  Google Scholar 

  12. Yang H-I, Yuen M-F, Chan HL-Y, Han K-H, Chen P-J, Kim D-Y, 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. https://doi.org/10.1016/s1470-2045(11)70077-8.

    Article  PubMed  Google Scholar 

  13. Lee HW, Yoo EJ, Kim BK, Kim SU, Park JY, Kim DY, et al. Prediction of development of liver-related events by transient elastography in hepatitis B patients with complete virological response on antiviral therapy. Am J Gastroenterol. 2014;109(8):1241–9. https://doi.org/10.1038/ajg.2014.157.

    Article  CAS  PubMed  Google Scholar 

  14. • Wong VW, Chan SL, Mo F, Chan TC, Loong HH, Wong GL, et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. J Clin Oncol. 2010;28(10):1660–5. https://doi.org/10.1200/JCO.2009.26.2675Risk score developed based on common clinical and laboratory parameters accurately predicts risk of liver cancer in 10 years time.

    Article  CAS  PubMed  Google Scholar 

  15. • Wong GL-H, Chan HL-Y, Wong CK-Y, Leung C, Chan CY, Ho PP-L, et al. Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B. J Hepatol. 2014;60(2):339–45. https://doi.org/10.1016/j.jhep.2013.09.029Risk score is further optimized with improved negative predictve value by replacing clinical cirrhosis by liver stiffness measurement.

    Article  PubMed  Google Scholar 

  16. Chan HLY. Identifying hepatitis B carriers at low risk for hepatocellular carcinoma. Gastroenterology. 2012;142(5):1057–60. https://doi.org/10.1053/j.gastro.2012.03.013.

    Article  PubMed  Google Scholar 

  17. Wong GL, Chan HL, Choi PC, Chan AW, Yu Z, Lai JW, et al. Non-invasive algorithm of enhanced liver fibrosis and liver stiffness measurement with transient elastography for advanced liver fibrosis in chronic hepatitis B. Aliment Pharmacol Ther. 2014;39(2):197–208. https://doi.org/10.1111/apt.12559.

    Article  PubMed  Google Scholar 

  18. Liang LY, Wong VW, Tse YK, Yip TC, Lui GC, Chan HL, et al. Improvement in enhanced liver fibrosis score and liver stiffness measurement reflects lower risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2019;49(12):1509–17. https://doi.org/10.1111/apt.15269.

    Article  CAS  PubMed  Google Scholar 

  19. Yuen MF, Tanaka Y, Fong DY, Fung J, Wong DK, Yuen JC, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;50(1):80–8. https://doi.org/10.1016/j.jhep.2008.07.023.

    Article  PubMed  Google Scholar 

  20. Yang HI, Sherman M, Su J, Chen PJ, Liaw YF, Iloeje UH, et al. Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J Clin Oncol. 2010;28(14):2437–44. https://doi.org/10.1200/JCO.2009.27.4456.

    Article  PubMed  Google Scholar 

  21. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98. https://doi.org/10.1007/s12072-015-9675-4.

    Article  CAS  PubMed  Google Scholar 

  22. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98. https://doi.org/10.1016/j.jhep.2017.03.021.

    Article  Google Scholar 

  23. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–99. https://doi.org/10.1002/hep.29800.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wong GL, Chan HL, Chan HY, Tse PC, Tse YK, Mak CW, et al. Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment. Gastroenterology. 2013;144(5):933–44. https://doi.org/10.1053/j.gastro.2013.02.002.

    Article  PubMed  Google Scholar 

  25. Arends P, Sonneveld MJ, Zoutendijk R, Carey I, Brown A, Fasano M, et al. Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians. Gut. 2015;64(8):1289–95. https://doi.org/10.1136/gutjnl-2014-307023.

    Article  CAS  PubMed  Google Scholar 

  26. Kim WR, Loomba R, Berg T, Aguilar Schall RE, Yee LJ, Dinh PV, et al. Impact of long-term tenofovir disoproxil fumarate on incidence of hepatocellular carcinoma in patients with chronic hepatitis B. Cancer. 2015;121(20):3631–8. https://doi.org/10.1002/cncr.29537.

    Article  CAS  PubMed  Google Scholar 

  27. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73. https://doi.org/10.1001/jama.295.1.65.

    Article  CAS  PubMed  Google Scholar 

  28. Wong GL, Wong VW, Chan HY, Tse PC, Wong J, Chim AM, et al. Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBeAg-seroconversion in chronic hepatitis B patients at 3 years. Aliment Pharmacol Ther. 2012;35(11):1326–35. https://doi.org/10.1111/j.1365-2036.2012.05098.x.

    Article  CAS  PubMed  Google Scholar 

  29. • Wong GL, Chan HL, Tse YK, Yip TC, Lam KL, Lui GC, et al. Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B. J Hepatol. 2018;69(4):793–802. https://doi.org/10.1016/j.jhep.2018.05.009Early ALT normalization during antiviral treatment is associated with lower risk of liver cancer.

    Article  CAS  PubMed  Google Scholar 

  30. Papatheodoridis G, Dalekos G, Sypsa V, Yurdaydin C, Buti M, Goulis J, et al. PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. J Hepatol. 2016;64(4):800–6. https://doi.org/10.1016/j.jhep.2015.11.035.

    Article  CAS  PubMed  Google Scholar 

  31. Kim JH, Kim YD, Lee M, Jun BG, Kim TS, Suk KT, et al. Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy. J Hepatol. 2018;69(5):1066–73. https://doi.org/10.1016/j.jhep.2018.07.018.

    Article  PubMed  Google Scholar 

  32. Lee HW, Kim SU, Park JY, Kim DY, Ahn SH, Han KH, et al. External validation of the modified PAGE-B score in Asian chronic hepatitis B patients receiving antiviral therapy. Liver Int. 2019;39(9):1624–30. https://doi.org/10.1111/liv.14129.

    Article  CAS  PubMed  Google Scholar 

  33. • Yip TC, Wong GL, Wong VW, Tse YK, Liang LY, Hui VW, et al. Reassessing the accuracy of PAGE-B-related scores to predict hepatocellular carcinoma development in patients with chronic hepatitis B. J Hepatol. 2019. https://doi.org/10.1016/j.jhep.2019.12.005PAGE-B and mPAGE-B identify patients with low risk of liver cancer after antiviral treatment so that cancer surveillance may be no longer needed.

  34. Kim SU, Seo YS, Lee HA, Kim MN, Kim EH, Kim HY, et al. Validation of the CAMD score in patients with chronic hepatitis B virus infection receiving antiviral therapy. Clin Gastroenterol Hepatol. 2020;18(3):693–9 e1. https://doi.org/10.1016/j.cgh.2019.06.028.

    Article  CAS  PubMed  Google Scholar 

  35. Kirino S, Tamaki N, Kaneko S, Kurosaki M, Inada K, Yamashita K, et al. Validation of hepatocellular carcinoma risk scores in Japanese chronic hepatitis B cohort receiving nucleot(s)ide analog. J Gastroenterol Hepatol. 2020. https://doi.org/10.1111/jgh.14990.

  36. Papatheodoridis GV, Sypsa V, Dalekos GN, Yurdaydin C, Van Boemmel F, Buti M, et al. Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B. J Hepatol. 2020;72:1088–96. https://doi.org/10.1016/j.jhep.2020.01.007.

    Article  CAS  PubMed  Google Scholar 

  37. Voulgaris T, Papatheodoridi M, Lampertico P, Papatheodoridis GV. Clinical utility of hepatocellular carcinoma risk scores in chronic hepatitis B. Liver Int. 2020;40(3):484–95. https://doi.org/10.1111/liv.14334.

    Article  PubMed  Google Scholar 

  38. Wong VW, Janssen HL. Can we use HCC risk scores to individualize surveillance in chronic hepatitis B infection? J Hepatol. 2015;63(3):722–32. https://doi.org/10.1016/j.jhep.2015.05.019.

    Article  PubMed  Google Scholar 

  39. Amarapurkar D, Han KH, Chan HL, Ueno Y. Asia-Pacific working party on prevention of hepatocellular C. Application of surveillance programs for hepatocellular carcinoma in the Asia-Pacific region. J Gastroenterol Hepatol. 2009;24(6):955–61. https://doi.org/10.1111/j.1440-1746.2009.05805.x.

    Article  PubMed  Google Scholar 

  40. Wong GL, Lampertico P. Residual risk of HCC during long-term oral nucleos(t)ide analogues (NUCs) in patients with CHB - is one NUC better than the other? J Hepatol. 2019;71(3):453–5. https://doi.org/10.1016/j.jhep.2019.05.017.

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Health and Medical Research Fund (HMRF) of the Food and Health Bureau (Reference no: 15160551) awarded to Grace Wong.

Author information

Authors and Affiliations

  1. Institute of Digestive Disease, Hong Kong, SAR, China

    Terry Cheuk-Fung Yip, Lilian Yan Liang & Grace Lai-Hung Wong

  2. Department of Medicine and Therapeutics, Prince of Wales Hospital, 9/F Lui Che Woo Clinical Sciences Building, 30-32 Ngan Shing Street, Shatin, Hong Kong

    Terry Cheuk-Fung Yip, Lilian Yan Liang & Grace Lai-Hung Wong

  3. Medical Data Analytic Centre (MDAC), The Chinese University of Hong Kong, Hong Kong, SAR, China

    Terry Cheuk-Fung Yip & Grace Lai-Hung Wong

Authors
  1. Terry Cheuk-Fung Yip
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lilian Yan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Grace Lai-Hung Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors were responsible for the interpretation of data and critical revision of the manuscript

Corresponding author

Correspondence to Grace Lai-Hung Wong.

Ethics declarations

Conflict of Interest

Terry Yip has served as a speaker for Gilead Sciences. Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen and as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen, and Roche. Lilian Liang declares that she has no competing interests.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Hepatitis B

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yip, T.CF., Liang, L.Y. & Wong, G.LH. Assessment of HCC Risk in Patients with Chronic HBV (REACH, PAGE-B, and Beyond). Curr Hepatology Rep 19, 285–292 (2020). https://doi.org/10.1007/s11901-020-00526-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-020-00526-w

Keywords

Search

Navigation