Skip to main content

Advertisement

SpringerLink
Log in

Clinical Course of Partial Virologic Response with Prolonged Tenofovir Therapy in Nuclos(t)ides-Naïve Patients with Chronic Hepatitis B

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background/Aims

The clinical course of chronic hepatitis B (CHB) patients with partial virologic response (PVR) during tenofovir disoproxil fumarate (TDF) therapy remains unclear.

Methods

We retrospectively investigated the long-term clinical outcomes of TDF treatment in nucleos(t)ides-naïve CHB patients, particularly in those with PVR.

Results

A total of 391 patients treated with TDF therapy for more than 12 months were included. Virologic response (VR) was achieved in 341 patients (87.2%). PVR was evident in 127 (45.3%) of the 391 patients. Multivariate logistic regression analysis using selected baseline factors identified absolute HBV DNA levels at baseline (OR 0.496; 95% CI 1.369–1.969) and HBeAg positivity (OR 0.622; 95% CI 1.096–3.167) as factors significantly associated with PVR. During continuous prolonged TDF therapy, 127 (71.8%) of 177 patients with PVR achieved VR. The cumulative rates of VR in patients with PVR at 12, 24, and 36 months were 42.4, 79.7, and 90.2%, respectively. Serum HBV DNA level at week 24 was significantly associated with VR in patients with PVR.

Conclusions

The vast majority of CHB patients with PVR achieved VR through prolonged TDF therapy, although the time to achieve VR was delayed in those with PVR. This suggests that adjustment of TDF therapy in patients with PVR is unnecessary.

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

Abbreviations

HBV:

Hepatitis B virus

NA:

Nucleos(t)ide

TDF:

Tenofovir disoproxil fumarate

ETV:

Entecavir

CHB:

Chronic hepatitis B

PVR:

Partial virologic response

HBeAg:

Hepatitis B e antigen

VR:

Virologic response

VBT:

Virologic breakthrough

CI:

Confidence interval

OR:

Odds ratio

ROC:

Receiver operating characteristic

AUROC:

Area under the ROC curve

HBsAg:

Hepatitis B surface antigen

References

  1. Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30:2212–2219.

    Article  CAS  PubMed  Google Scholar 

  2. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.

    Article  CAS  PubMed  Google Scholar 

  3. Levrero M, Testoni B, Zoulim F. HBV cure: Why, how, when? Curr Opin Virol. 2016;18:135–143.

    Article  PubMed  Google Scholar 

  4. Lampertico P, Maini M, Papatheodoridis G. Optimal management of hepatitis B virus infection—EASL special conference. J Hepatol. 2015;63:1238–1253.

    Article  PubMed  Google Scholar 

  5. Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1–98.

    Article  CAS  PubMed  Google Scholar 

  6. Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442–2455.

    Article  CAS  PubMed  Google Scholar 

  7. Buti M, Tsai N, Petersen J, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci. 2015;60:1457–1464.

    Article  CAS  PubMed  Google Scholar 

  8. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381:468–475.

    Article  CAS  PubMed  Google Scholar 

  9. Yuen MF, Sablon E, Hui CK, Yuan HJ, Decraemer H, Lai CL. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy. Hepatology. 2001;34:785–791.

    Article  CAS  PubMed  Google Scholar 

  10. Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology. 2006;131:1743–1751.

    Article  CAS  PubMed  Google Scholar 

  11. Liaw YF, Gane E, Leung N, et al. 2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 2009;136:486–495.

    Article  CAS  PubMed  Google Scholar 

  12. EASL clinical practice guidelines. Management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–185.

    Article  Google Scholar 

  13. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–662.

    Article  PubMed  Google Scholar 

  14. Zoutendijk R, Reijnders JG, Brown A, et al. Entecavir treatment for chronic hepatitis B: adaptation is not needed for the majority of naive patients with a partial virological response. Hepatology. 2011;54:443–451.

    Article  CAS  PubMed  Google Scholar 

  15. Ko SY, Choe WH, Kwon SY, et al. Long-term impact of entecavir monotherapy in chronic hepatitis B patients with a partial virologic response to entecavir therapy. Scand J Gastroenterol. 2012;47:1362–1367.

    Article  CAS  PubMed  Google Scholar 

  16. Bang SJ, Kim BG, Shin JW, et al. Clinical course of patients with insufficient viral suppression during entecavir therapy in genotype C chronic hepatitis B. Dig Liver Dis. 2013;45:600–605.

    Article  CAS  PubMed  Google Scholar 

  17. Choi HN, Song JE, Lee HC, Jo HH, Lee CH, Kim BS. Efficacy of prolonged entecavir monotherapy in treatment-naive chronic hepatitis B patients exhibiting a partial virologic response to entecavir. Clin Mol Hepatol. 2015;21:24–31.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Korean Association for the Study of the L. KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol. 2016;22:18–75.

    Article  Google Scholar 

  19. Ha NB, Ha NB, Garcia RT, et al. Medication nonadherence with long-term management of patients with hepatitis B e antigen-negative chronic hepatitis B. Dig Dis Sci. 2011;56:2423–2431.

    Article  PubMed  Google Scholar 

  20. Hongthanakorn C, Chotiyaputta W, Oberhelman K, et al. Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. Hepatology. 2011;53:1854–1863.

    Article  PubMed  Google Scholar 

  21. Liaw YF, Raptopoulou-Gigi M, Cheinquer H, et al. Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized, open-label study. Hepatology. 2011;54:91–100.

    Article  CAS  PubMed  Google Scholar 

  22. Kamezaki H, Kanda T, Wu S, et al. Emergence of entecavir-resistant mutations in nucleos(t)ide-naive Japanese patients infected with hepatitis B virus: virological breakthrough is also dependent on adherence to medication. Scand J Gastroenterol. 2011;46:1111–1117.

    Article  CAS  PubMed  Google Scholar 

  23. Chotiyaputta W, Peterson C, Ditah FA, Goodwin D, Lok AS. Persistence and adherence to nucleos(t)ide analogue treatment for chronic hepatitis B. J Hepatol. 2011;54:12–18.

    Article  CAS  PubMed  Google Scholar 

  24. Yuen MF, Seto WK, Fung J, Wong DK, Yuen JC, Lai CL. Three years of continuous entecavir therapy in treatment-naive chronic hepatitis B patients: VIRAL suppression, viral resistance, and clinical safety. Am J Gastroenterol. 2011;106:1264–1271.

    Article  CAS  PubMed  Google Scholar 

  25. Ono A, Suzuki F, Kawamura Y, et al. Long-term continuous entecavir therapy in nucleos(t)ide-naive chronic hepatitis B patients. J Hepatol. 2012;57:508–514.

    Article  CAS  PubMed  Google Scholar 

  26. Shin JW, Jung SW, Park BR, et al. Prediction of response to entecavir therapy in patients with HBeAg-positive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels. J Viral Hepat. 2012;19:724–731.

    Article  CAS  PubMed  Google Scholar 

  27. European Association For The Study Of The L. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–185.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by Priority Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2010-0029621).

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 887 Bangeojinsunhwando-ro, Dong-gu, Ulsan, 44033, Republic of Korea

    In Du Jeong, Seok Won Jung, Byung Uk Lee, Jae Ho Park, Byung Gyu Kim, Sung-Jo Bang, Jung Woo Shin & Neung Hwa Park

  2. Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea

    Bo Ryung Park & Neung Hwa Park

Authors
  1. In Du Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seok Won Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Ryung Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Byung Uk Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jae Ho Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Byung Gyu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sung-Jo Bang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jung Woo Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Neung Hwa Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neung Hwa Park.

Ethics declarations

Conflict of interest

The authors declared that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Du Jeong, I., Jung, S.W., Park, B.R. et al. Clinical Course of Partial Virologic Response with Prolonged Tenofovir Therapy in Nuclos(t)ides-Naïve Patients with Chronic Hepatitis B. Dig Dis Sci 62, 2908–2914 (2017). https://doi.org/10.1007/s10620-017-4737-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-017-4737-1

Keywords

Search

Navigation