Skip to main content

Advertisement

SpringerLink
Log in

Distinct on-treatment HCC risks associated with different decompensation events in HBV patients with cirrhosis

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Objectives

Long-term treatment with nucleoside analog (NA) reduces the risks for decompensation and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with compensated cirrhosis (CC). However, whether antiviral therapy has differential efficacy on the risks for decompensation and HCC is insufficiently elucidated. Therefore, we investigated the disease state transition, focusing on decompensation event-specific HCC risk in NA-treated CHB patients with CC.

Methods

We prospectively followed up on 1163 NA-treated CHB patients with CC every six months for up to seven years. The cumulative incidence and risk of HCC were analyzed by the Kaplan–Meier method and competing risk model. The multistate model was used to estimate the transition probabilities to HCC from different disease states.

Results

HCC predominated the first liver-related events, with a 5-year cumulative incidence of 9.0%, followed by decompensation (8.3%, including 7.9% nonbleeding decompensation and 2.4% variceal bleeding) and 0.2% death. The decompensation stage had a significantly higher 5-year cumulative HCC incidence than the CC stage (27.6% vs. 9.1%; HR = 2.42, 95% CI: 1.24, 4.71). Furthermore, nonbleeding decompensation events had a higher 5-year transition probability to HCC than bleeding (27.6% vs. 15.8%; HR = 2.69, 95% CI: 1.41, 4.17). Viral suppression modified the on-treatment transition risk to HCC (1-year: HR = 0.45, 95% CI: 0.28, 0.73; 3-year: HR = 0.23, 95% CI: 0.14, 0.38). An online calculator was developed to facilitate HCC risk stratification.

Conclusions

In NA-treated CHB patients with compensated cirrhosis, the risk was higher for HCC than for decompensation; more importantly, different decompensation events conferred distinct HCC risks.

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
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this article and its supplementary material files. Further enquiries can be directed to the corresponding author.

References

  1. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology. 2021;73(Suppl 1):4–13

    Article  CAS  PubMed  Google Scholar 

  2. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):S35-50

    Article  PubMed  Google Scholar 

  3. Jepsen P, Vilstrup H, Andersen PK, Lash TL, Sørensen HT. Comorbidity and survival of Danish cirrhosis patients: a nationwide population-based cohort study. Hepatology. 2008;48:214–220

    Article  PubMed  Google Scholar 

  4. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–1273

    Article  PubMed  Google Scholar 

  5. Papatheodoridis GV, Chan HL, Hansen BE, Janssen HL, Lampertico P. Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy. J Hepatol. 2015;62(4):956–967

    Article  PubMed  Google Scholar 

  6. Alqahtani SA, Colombo M. Treatment for viral hepatitis as secondary prevention for hepatocellular carcinoma. Cells. 2021;10(11):3091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Liu M, Tseng TC, Jun DW, et al. Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients. Hepatol Int. 2021;15(1):71–81

    Article  PubMed  Google Scholar 

  8. Fan R, Papatheodoridis G, Sun J, Innes H, Toyoda H, Xie Q, et al. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol. 2020;73(6):1368–1378

    Article  CAS  PubMed  Google Scholar 

  9. Wu SS, Zeng N, Sun F, Zhou JL, Wu XN, Sun YM, et al. Hepatocellular carcinoma prediction models in chronic hepatitis B. Clin Gastroenterol Hepatol. 2021;19(12):2499–2513

    Article  CAS  PubMed  Google Scholar 

  10. D’Amico G, Pasta L, Morabito A, D’Amico M, Caltagirone M, Malizia G, et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther. 2014;39(10):1180–1193

    Article  PubMed  Google Scholar 

  11. D’Amico G, Bernardi M, Angeli P. Towards a new definition of decompensated cirrhosis. J Hepatol. 2022;76(1):202–207

    Article  PubMed  Google Scholar 

  12. Wu XN, Zhou JL, Sun YM, Ding HG, Chen GF, Xie W, et al. Prediction of liver-related events in patients with compensated HBV-induced cirrhosis receiving antiviral therapy. Hepatol Int. 2021;15(1):82–92

    Article  PubMed  Google Scholar 

  13. Wu XN, Shi YW, Zhou JL, Sun YM, Piao HX, Jiang W, et al. Combination of entecavir with thymosin alpha-1 in HBV-related compensated cirrhosis: a prospective multicenter randomized open-label study. Expert Opin Biol Ther. 2018;18(sup1):61–69

    Article  CAS  PubMed  Google Scholar 

  14. Esterson YB, Grimaldi GM. Radiologic imaging in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis. 2018;22(1):93–108

    Article  PubMed  Google Scholar 

  15. Franchis RD, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C. Baveno VII faculty. Baveno VII—renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–74

    Article  PubMed  Google Scholar 

  16. D’Amico G, Morabito A, D’Amico M, Pasta L, Malizia G, Rebora P, et al. Clinical states of cirrhosis and competing risks. J Hepatol. 2018;68(3):563–576

    Article  PubMed  Google Scholar 

  17. Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med. 2007;26(11):2389–2430

    Article  CAS  PubMed  Google Scholar 

  18. Efron B. Bootstrap methods: another look at the jackknife. Ann Stat. 1979;7(1):1–26

    Article  Google Scholar 

  19. Andersen PK, Keiding N. Multistate models for event history analysis. Stat Methods Med Res. 2002;11(2):91–115

    Article  PubMed  Google Scholar 

  20. Wreede LC, Fiocco M, Putter H. The mstate package for estimation and prediction in non- and semi-parametric multi-state and competing risks models. Comput Methods Programs Biomed. 2010;99(3):261–274

    Article  PubMed  Google Scholar 

  21. Møller S, Hobolth L, Winkler C, Bendtsen F, Christensen E. Determinants of the hyperdynamic circulation and central hypovolaemia in cirrhosis. Gut. 2011;60(9):1254–1259

    Article  PubMed  Google Scholar 

  22. World Health Organization. Guidelines for the Prevention, Care and Treatment of Persons With Chronic Hepatitis B Infection. Geneva, Switzerland: World Health Organization, 2015[Cited 2015 March 1]. Available from: https://www.who.int/publications/i/item/9789241549059.

  23. Levrero M, Zucman-Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol. 2016;64(1 Suppl):S84–S101

    Article  CAS  PubMed  Google Scholar 

  24. Bousali M, Papatheodoridis G, Paraskevis D, Karamitros T. Hepatitis B virus DNA integration, chronic infections and hepatocellular carcinoma. Microorganisms. 2021;9(8):1787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the american association for the study of liver diseases. Hepatology. 2018;68(2):723–750

    Article  PubMed  Google Scholar 

  26. D’Amico G, Abraldes JG, Rebora P, Valsecchi MG, Garcia-Tsao G. Ordinal outcomes are superior to binary outcomes for designing and evaluating clinical trials in compensated cirrhosis. Hepatology. 2020;72(3):1029–1042

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to express our sincere thanks to the investigators from the participating hospitals for recruiting the patients and collecting the data. We thank Shanghai Ashermed Healthcare Communications Ltd for the technical support in developing the online calculator for the multistate HBV model.

Funding

The Project of the High-level Public Health Professional Talents of the Beijing Municipal Health Commission (XUEKEGUGAN-010-018), the National Major Science and Technology Project (2017ZX10203202-003), and the Project of the Beijing Municipal Commission of Science and Technology (D161100002716003, Z191100007619037).

Author information

Authors and Affiliations

  1. Clinical Epidemiology & EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Yuanyuan Kong & Hao Wang

  2. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Yameng Sun, Xiaoning Wu, Jialing Zhou, Xiaojuan Ou & Jidong Jia

  3. Department of Gastroenterology and Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China

    Huiguo Ding

  4. Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China

    Wen Xie

  5. Division of Liver Fibrosis, The Fifth Medical Center, General Hospital of the People’s Liberation Army, Beijing, China

    Guofeng Chen

  6. Division of Infectious Diseases, China-Japan Friendship Hospital, Beijing, China

    Anlin Ma

  7. Infectious Disease Department, Affiliated Hospital of Yanbian University, Yanji, Jilin, China

    Hongxin Piao

  8. Division of Infectious Diseases, Peking University First Hospital, Beijing, China

    Xiaoyuan Xu

  9. Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China

    Wei Jiang

  10. Hepatology Institution, Peking University People’s Hospital, Beijing, China

    Bo Feng

  11. Beijing Key Laboratory of Translational Medicine On Liver Cirrhosis, Beijing Clinical Research Institute, Beijing, China

    Hong You

  12. Liver Unit, Cumming School of Medicine, University of Calgary, Calgary, Canada

    Samuel S. Lee

  13. National Clinical Research Center for Digestive Diseases, Beijing, China

    Yuanyuan Kong & Jidong Jia

Authors
  1. Yuanyuan Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yameng Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoning Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jialing Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huiguo Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wen Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Guofeng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anlin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hongxin Piao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xiaoyuan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Wei Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Bo Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Xiaojuan Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Hong You
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Samuel S. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jidong Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Hong You and Jidong Jia supervised the study. Yuanyuan Kong designed, analyzed, and interpreted data and drafted the manuscript. Yameng Sun and Xiaoning Wu performed clinical studies and reviewed clinical outcomes. Hao Wang drew the Sankey diagram. Jialing Zhou, Huiguo Ding, Wen Xie, Guofeng Chen, Anlin Ma, Hongxin Piao, Xiaoyuan Xu, Wei Jiang, Bo Feng, Jilin Cheng, and Xiaojuan Ou performed clinical studies. Hong You, Samuel S. Lee, and Jidong Jia critically revised the manuscript. All authors approved the final manuscript.

Corresponding authors

Correspondence to Hong You, Samuel S. Lee or Jidong Jia.

Ethics declarations

Conflict of interest

Yuanyuan Kong received consulting fees or speaker honoraria from Gilead and Hansoh. Hong You and Jidong Jia received research grants, consulting fees, or speaker honoraria from BMS, Gilead, and GSK. Samuel S. Lee received research grants, consulting fees, or speaker honoraria from Gilead, Novartis, and Roche. The other authors declare no conflict of interest concerning this manuscript.

Ethical approval

The study protocol was reviewed and approved by the ethics committee of Beijing Friendship Hospital, Capital Medical University (approval number: 2016-P2-021-04, 2016-P2-022-02). All study-related procedures and data collection were conducted in accordance with the Declaration of Helsinki and following the Good Clinical Practice standards.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 789 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kong, Y., Sun, Y., Wu, X. et al. Distinct on-treatment HCC risks associated with different decompensation events in HBV patients with cirrhosis. Hepatol Int 17, 1350–1358 (2023). https://doi.org/10.1007/s12072-023-10567-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-023-10567-0

Keywords

Search

Navigation