본문 바로가기
KERD
논문KCI 등재

Efficacy and Safety of Tenofovir-Based Rescue Therapy for Chronic Hepatitis B Patients with Previous Nucleo(s/t)ide Treatment Failure

2

조회

0

다운로드

5

인용

0

참고문헌

키워드

초록

Background/Aims: We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies. Methods: Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored. Results: Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log10 IU/mL to 2.0 log10 IU/mL and to 1.6 log10 IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed. Conclusions: TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients’ adherence to medication is related to viral rebound.

Abstract

Background/Aims: We investigated the efficacy and safety of tenofovir disoproxil fumarate (TDF)-based treatment in chronic hepatitis B (CHB) patients who failed previous antiviral therapies. Methods: Seventeen patients who failed to achieve virological responses during sequential antiviral treatments were included. The patients were treated with TDF monotherapy (four patients) or a combination of TDF and lamivudine (13 patients) for a median of 42 months. Hepatitis B virus (HBV) DNA and hepatitis B e antigen (HBeAg) were measured, and renal function was also monitored. Results: Prior to TDF therapy, 180 M, 204 I/V/S, 181 T/V, 236 T, and 184 L mutations were detected. After TDF therapy, the median HBV DNA level decreased from 4.6 log10 IU/mL to 2.0 log10 IU/mL and to 1.6 log10 IU/mL at 12 and 24 months, respectively. HBV DNA became undetectable (≤20 IU/mL) in 14.3%, 41.7%, and 100% of patients after 12, 24, and 48 months of treatment, respectively. HBeAg loss was observed in two patients. Viral breakthrough occurred in five patients who had skipped their medication. No significant changes in renal function were observed. Conclusions: TDF-based rescue treatment is effective in reducing HBV DNA levels and is safe for patients with CHB who failed prior antiviral treatments. Patients’ adherence to medication is related to viral rebound.

참고문헌 (25)

  1. European Association for the Study of the Liver, "EASL clinical practice guidelines: management of chronic hepatitis B", J Hepatol, 50, pp.227~242 (2009)
  2. Lok AS, "Chronic hepatitis B", Hepatology, 45, pp.507~539 (2007)
  3. Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
  4. Marcellin P, "Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B", N Engl J Med, 348, pp.808~816 (2003)
  5. Yotsuyanagi H, "Drug resistance in antiviral treatment for infections with hepatitis B and C viruses", J Gastroenterol, 42, pp.329~335 (2007)
  6. Lok AS, "Long-term safety of lamivudine treatment in patients with chronic hepatitis B", Gastroenterology, 125, pp.1714~1722 (2003)
  7. Marcellin P, "Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B", Hepatology, 48, pp.750~758 (2008)
  8. Marcellin P, "Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B", N Engl J Med, 359, pp.2442~2455 (2008)
  9. Patterson SJ, "Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B", Gut, 60, pp.247~254 (2011)
  10. Pan CQ, "Response to tenofovir monotherapy in chronic hepatitis B patients with prior suboptimal response to entecavir", J Viral Hepat, 19, pp.213~219 (2012)
  11. Petersen J, "Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients: an international multicenter cohort study", J Hepatol, 56, pp.520~526 (2012)
  12. Lee YS, "Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48 weeks of adefovir dipivoxil monotherapy", Hepatology, 43, pp.1385~1391 (2006)
  13. Fung SK, "Virologic response and resistance to adefovir in patients with chronic hepatitis B", J Hepatol, 44, pp.283~290 (2006)
  14. Kim HJ, "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, 25, pp.1374~1380 (2010)
  15. Ying C, "Lamivudine, adefovir and tenofovir exhibit long-lasting anti-hepatitis B virus activity in cell culture", J Viral Hepat, 7, pp.79~83 (2000)
  16. Ying C, "Inhibition of the replication of the DNA polymerase M550V mutation variant of human hepatitis B virus by adefovir, tenofovir, L-FMAU, DAPD, penciclovir and lobucavir", J Viral Hepat, 7, pp.161~165 (2000)
  17. n Bommel F, "Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy", Hepatology, 44, pp.318~325 (2006)
  18. Hongthanakorn C, "Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice", Hepatology, 53, pp.1854~1863 (2011)
  19. Qi X, "In vitro susceptibility of adefovir-associated hepatitis B virus polymerase mutations to other antiviral agents", Antivir Ther, 12, pp.355~362 (2007)
  20. Berg T, "Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection", Gastroenterology, 139, pp.1207~1217 (2010)
  21. Tan J, "Tenofovir monotherapy is effective in hepatitis B patients with antiviral treatment failure to adefovir in the absence of adefovir-resistant mutations", J Hepatol, 48, pp.391~398 (2008)
  22. Hall AM, "Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence", Am J Kidney Dis, 57, pp.773~780 (2011)
  23. Heathcote EJ, "Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B", Gastroenterology, 140, pp.132~143 (2011)
  24. Amini-Bavil-Olyaee S, "The rtA194T polymerase mutation impacts viral replication and susceptibility to tenofovir in hepatitis B e antigen-positive and hepatitis B e antigen-negative hepatitis B virus strains", Hepatology, 49, pp.1158~1165 (2009)
  25. Delaney WE 4th, "Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus", Antimicrob Agents Chemother, 50, pp.2471~2477 (2006)

관련 논문AI추천

Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir김형래, 노진희, 박능화, 신정우, 안재성, 양유진, 이재호, 전희정, 정석원대한간학회 · Clinical and Molecular Hepatology2017 · 제23권 제3호Comparison of tenofovir plus lamivudine versus tenofovir monotherapy in patients with lamivudine-resistant chronic hepatitis B박능화, 박용태, 박찬호, 배미애, 신정우, 이윤임, 정석원, 정화식대한간학회 · Clinical and Molecular Hepatology2016 · 제22권 제1호Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response김동준, Chang Wook Kim, Hyun Young Woo, In Hee Kim, Jae Young Jang, Jeong Heo, Jun Yong Park, Sang Hoon Ahn, Si Hyun Bae, Won Young Tak대한간학회 · Clinical and Molecular Hepatology2020 · 제26권 제3호The efficacy of Tenofovir-based therapy in patients showing suboptimal response to Entecavir-Adefovr combination therapy고순영, 권소영, 김균환, 김정한, 안성현, 최원혁대한간학회 · Clinical and Molecular Hepatology2016 · 제22권 제2호Long-term outcomes of two rescue therapies in lamivudine- refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir권재철, 김형준, 백은경, 안대건, 이종진, 이현웅, 정한욱, 제은영, 조환준대한간학회 · Clinical and Molecular Hepatology2014 · 제20권 제3호Tenofovir has inferior efficacy in adefovir-experienced chronic hepatitis B patients compared to nucleos(t)idenaïve patients김윤준, 김휘영, 유수종, 유정주, 윤정환, 이동현, 이민종, 이정훈, 정고은, 조유리, 조은주, Fabien Zoulim대한간학회 · Clinical and Molecular Hepatology2017 · 제23권 제1호

이 간행물의 다른 논문 (16건)