DOI QR코드

DOI QR Code

Long-term efficacy of tenofovir disoproxil fumarate therapy after multiple nucleos(t)ide analogue failure in chronic hepatitis B patients

  • Kim, Hyo Jin (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Cho, Ju-Yeon (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Yu Jin (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Gwak, Geum-Youn (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Paik, Yong-Han (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Moon Seok (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koh, Kwang Cheol (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Paik, Seung Woon (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yoo, Byung Chul (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Joon Hyeok (Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2014.06.13
  • Accepted : 2014.08.01
  • Published : 2015.01.01

Abstract

Background/Aims: The efficacy of tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B (CHB) patients following prior treatment failure with multiple nucleos(t)ide analogues (NAs) is not well defined, especially in Asian populations. In this study we investigated the efficacy and safety of TDF rescue therapy in CHB patients after multiple NA treatment failure. Methods: The study retrospectively analyzed 52 CHB patients who experienced failure with two or more NAs and who were switched to regimens containing TDF. The efficacy and safety assessments included hepatitis B virus (HBV) DNA undetectability, hepatitis B envelop antigen (HBeAg) seroclearance, alanine transaminase (ALT) normalization and changes in serum creatinine and phosphorus levels. Results: The mean HBV DNA level at baseline was $5.4{\pm}1.76log_{10}\;IU/mL$. At a median duration of 34.5 months of TDF treatment, the cumulative probabilities of achieving complete virological response (CVR) were 25.0%, 51.8%, 74.2%, and 96.7% at 6, 12, 24, and 48 months, respectively. HBeAg seroclearance occurred in seven of 48 patients (14.6%). ALT levels were normalized in 27 of 31 patients (87.1%) with elevated ALT at baseline. Lower levels of HBV DNA at baseline were significantly associated with increased CVR rates (p < 0.001). However, CVR rates did not differ between TDF monotherapy or combination therapy with other NAs, and were not affected by mutations associated with resistance to NAs. No significant adverse events were observed. Conclusions: TDF is an efficient and safe rescue therapy for CHB patients after treatment failure with multiple NAs.

Keywords

References

  1. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol 2012;57:167-185. https://doi.org/10.1016/j.jhep.2012.02.010
  2. Korean Association for the Study of the Liver. KASL Clinical Practice Guidelines: management of chronic hepatitis B. Clin Mol Hepatol 2012;18:109-162. https://doi.org/10.3350/cmh.2012.18.2.109
  3. Dienstag JL. Benefits and risks of nucleoside analog therapy for hepatitis B. Hepatology 2009;49(5 Suppl):S112-S121. https://doi.org/10.1002/hep.22920
  4. Liaw YF. Hepatitis B virus replication and liver disease progression: the impact of antiviral therapy. Antivir Ther 2006;11:669-679.
  5. Chang TT, Liaw YF, Wu SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology 2010;52:886-893. https://doi.org/10.1002/hep.23785
  6. Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009;50:661-662. https://doi.org/10.1002/hep.23190
  7. Ghany MG, Doo EC. Antiviral resistance and hepatitis B therapy. Hepatology 2009;49(5 Suppl):S174-S184. https://doi.org/10.1002/hep.22900
  8. 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. https://doi.org/10.1002/hep.24318
  9. Lok AS, Lai CL, Leung N, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology 2003;125:1714-1722. https://doi.org/10.1053/j.gastro.2003.09.033
  10. Lee YS, Suh DJ, Lim YS, et al. Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy. Hepatology 2006;43:1385-1391. https://doi.org/10.1002/hep.21189
  11. Yeon JE, Yoo W, Hong SP, et al. Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil. Gut 2006;55:1488-1495. https://doi.org/10.1136/gut.2005.077099
  12. Rapti I, Dimou E, Mitsoula P, Hadziyannis SJ. Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology 2007;45:307-313. https://doi.org/10.1002/hep.21534
  13. Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology 2009;49:1503-1514. https://doi.org/10.1002/hep.22841
  14. Kim HJ, Park JH, Park DI, et al. Rescue therapy for lamivudine-resistant chronic hepatitis B: comparison between entecavir 1.0 mg monotherapy, adefovir monotherapy and adefovir add-on lamivudine combination therapy. J Gastroenterol Hepatol 2010;25:1374-1380. https://doi.org/10.1111/j.1440-1746.2010.06381.x
  15. Ryu HJ, Lee JM, Ahn SH, et al. Efficacy of adefovir add-on lamivudine rescue therapy compared with switching to entecavir monotherapy in patients with lamivudine-resistant chronic hepatitis B. J Med Virol 2010;82:1835-1842. https://doi.org/10.1002/jmv.21898
  16. Heathcote EJ, Marcellin P, Buti M, et al. Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B. Gastroenterology 2011;140:132-143. https://doi.org/10.1053/j.gastro.2010.10.011
  17. Snow-Lampart A, Chappell B, Curtis M, et al. No resistance to tenofovir disoproxil fumarate detected after up to 144 weeks of therapy in patients monoinfected with chronic hepatitis B virus. Hepatology 2011;53:763-773. https://doi.org/10.1002/hep.24078
  18. Patterson SJ, George J, Strasser SI, et al. Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B. Gut 2011;60:247-254. https://doi.org/10.1136/gut.2010.223206
  19. van Bommel F, de Man RA, Wedemeyer H, et al. Longterm efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues. Hepatology 2010;51:73-80. https://doi.org/10.1002/hep.23246
  20. Kim YJ, Sinn DH, Gwak GY, et al. Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures. World J Gastroenterol 2012;18:6996-7002. https://doi.org/10.3748/wjg.v18.i47.6996
  21. Shin SR, Yoo BC, Choi MS, et al. A comparison of 48-week treatment efficacy between clevudine and entecavir in treatment-naive patients with chronic hepatitis B. Hepatol Int 2011;5:664-670. https://doi.org/10.1007/s12072-010-9238-7
  22. Lada O, Benhamou Y, Cahour A, Katlama C, Poynard T, Thibault V. In vitro susceptibility of lamivudine-resistant hepatitis B virus to adefovir and tenofovir. Antivir Ther 2004;9:353-363.
  23. Kuo A, Dienstag JL, Chung RT. Tenofovir disoproxil fumarate for the treatment of lamivudine-resistant hepatitis B. Clin Gastroenterol Hepatol 2004;2:266-272. https://doi.org/10.1016/S1542-3565(04)00017-5
  24. van Bommel F, Wunsche T, Mauss S, et al. Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. Hepatology 2004;40:1421-1425. https://doi.org/10.1002/hep.20464
  25. Hann HW, Chae HB, Dunn SR. Tenofovir (TDF) has stronger antiviral effect than adefovir (ADV) against lamivudine (LAM)-resistant hepatitis B virus (HBV). Hepatol Int 2008;2:244-249. https://doi.org/10.1007/s12072-008-9045-6
  26. van Bommel F, Zollner B, Sarrazin C, et al. Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy. Hepatology 2006;44:318-325. https://doi.org/10.1002/hep.21253
  27. Qi X, Xiong S, Yang H, Miller M, Delaney WEt. In vitro susceptibility of adefovir-associated hepatitis B virus polymerase mutations to other antiviral agents. Antivir Ther 2007;12:355-362.
  28. Delaney WEt, Ray AS, Yang H, et al. Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus. Antimicrob Agents Chemother 2006;50:2471-2477. https://doi.org/10.1128/AAC.00138-06
  29. Petersen J, Ratziu V, Buti M, et al. Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients: an international multicenter cohort study. J Hepatol 2012;56:520-526. https://doi.org/10.1016/j.jhep.2011.09.018
  30. Tujios SR, Lee WM. Update in the management of chronic hepatitis B. Curr Opin Gastroenterol 2013;29:250-256. https://doi.org/10.1097/MOG.0b013e32835ff1e9
  31. Song BC, Cui XJ, Kim H. Hepatitis B virus genotypes in Korea: an endemic area of hepatitis B virus infection. Intervirology 2005;48:133-137. https://doi.org/10.1159/000081740
  32. Cho JH, Yoon KH, Lee KE, et al. Distribution of hepatitis B virus genotypes in Korea. Korean J Hepatol 2009;15:140-147. https://doi.org/10.3350/kjhep.2009.15.2.140
  33. Lee JM, Park JY, Kim do Y, et al. Long-term adefovir dipivoxil monotherapy for up to 5 years in lamivudine-resistant chronic hepatitis B. Antivir Ther 2010;15:235-241. https://doi.org/10.3851/IMP1510

Cited by

  1. Is tenofovir disoproxil fumarate an all-powerful weapon in the treatment of chronic hepatitis B? vol.30, pp.1, 2015, https://doi.org/10.3904/kjim.2015.30.1.23
  2. Antiviral Therapy in Lamivudine-Resistant Chronic Hepatitis B Patients: A Systematic Review and Network Meta-Analysis vol.2016, pp.None, 2015, https://doi.org/10.1155/2016/3435965
  3. The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy vol.22, pp.2, 2015, https://doi.org/10.3350/cmh.2015.0053
  4. Is the tenofovir based therapy almighty for previous treatment failure in chronic hepatitis B? vol.22, pp.2, 2016, https://doi.org/10.3350/cmh.2016.0103
  5. Efficacy and Safety of Tenofovir Disoproxil Treatment for Chronic Hepatitis B Patients with Genotypic Resistance to Other Nucleoside Analogues: A Prospective Study vol.130, pp.8, 2017, https://doi.org/10.4103/0366-6999.204107
  6. Management of Clevudine-Resistant Chronic Hepatitis B: A Multicenter Cohort Study vol.11, pp.1, 2015, https://doi.org/10.5009/gnl15597
  7. Treatment Efficacy and Safety of Tenofovir-Based Therapy in Chronic Hepatitis B: A Real Life Cohort Study in Korea vol.12, pp.1, 2017, https://doi.org/10.1371/journal.pone.0170362
  8. Real World Experience of Telbivudine Versus Entecavir in Patients with Chronic Hepatitis B, Including Long-Term Outcomes after Treatment Modification vol.59, pp.3, 2015, https://doi.org/10.3349/ymj.2018.59.3.383
  9. Risk factors associated with hypophosphatemia in chronic Hepatitis B patients treated with tenofovir disoproxil fumarate vol.98, pp.50, 2015, https://doi.org/10.1097/md.0000000000018351
  10. Adverse events of nucleos(t)ide analogues for chronic hepatitis B: a systematic review vol.55, pp.5, 2015, https://doi.org/10.1007/s00535-020-01680-0
  11. Tenofovir disoproxil fumarate for patients with chronic hepatitis B who suboptimal response to non‐tenofovir disoproxil fumarate nucleos(t)ide analogs therapy vol.7, pp.4, 2015, https://doi.org/10.1002/aid2.13171
  12. Tenofovir‐based combination therapy or monotherapy for multidrug‐resistant chronic hepatitis B: Long‐term data from a multicenter cohort study vol.27, pp.12, 2015, https://doi.org/10.1111/jvh.13363
  13. Guidelines for Prevention and Treatment of Chronic Hepatitis B vol.n, pp.None, 2015, https://doi.org/10.14218/jcth.2021.00209