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Virologic response is not durable after adefovir discontinuation in lamivudine-resistant chronic hepatitis B patients

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Background/Aims: We investigated the durability of the biochemical and virologic responses after adefovir (ADV)discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance. Methods: The indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay, <70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 105 copies/mL. Results: In the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range,3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than 105 copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough. Conclusions: During short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore,the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group.

Abstract

Background/Aims: We investigated the durability of the biochemical and virologic responses after adefovir (ADV)discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance. Methods: The indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay, <70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 105 copies/mL. Results: In the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range,3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than 105 copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough. Conclusions: During short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore,the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group.

참고문헌 (25)

  1. Hadziyannis SJ, "Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B", N Engl J Med, 352, pp.2673~2681 (2005)
  2. Lok AS, "Chronic hepatitis B", Hepatology, 45, pp.507~539 (2007)
  3. 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)
  4. Wu IC, "Sustained hepatitis B e antigen seroconversion in patients with chronic hepatitis B after adefovir dipivoxil treatment: analysis of precore and basal core promoter mutants", Clin Infect Dis, 47, pp.1305~1311 (2008)
  5. Hadziyannis S, "Sustained biochemical and virological remission after discontinuation of 4 to 5 years of adefovir dipivoxil (ADV) treatment in HBeAg-negative chronic hepatitis B", Hepatology, 44(1), pp.231~ (2006)
  6. Perrillo R, "Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus", Gastroenterology, 126, pp.81~90 (2004)
  7. Peters MG, "Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B", Gastroenterology, 126, pp.91~101 (2004)
  8. Kim do Y, "Efficacy of adefovir dipivoxil in the treatment of lamivudineresistant hepatitis B virus genotype C infection", Liver Int, 27, pp.47~53 (2007)
  9. Gaia S, "Lamivudine-resistant chronic hepatitis B: an observational study on adefovir in monotherapy or in combination with lamivudine", J Hepatol, 48, pp.540~547 (2008)
  10. Liaw YF, "Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update", Hepatol Int, 2, pp.263~283 (2008)
  11. Young Kul Jung, "Virologic Response at 12 Months of Treatment Predicts Sustained Antiviral Efficacy in Patients with Adefovir-Treated Lamivudine-Resistant Chronic Hepatitis B", Gut and Liver, 4(2), pp.212~218 (2010), 거트앤리버 발행위원회
  12. European Association For The Study Of The Liver, "EASL Clinical Practice Guidelines: management of chronic hepatitis B", J Hepatol, 50, pp.227~242 (2009)
  13. Raimondo G, "Statements from the Taormina expert meeting on occult hepatitis B virus infection", J Hepatol, 49, pp.652~657 (2008)
  14. van Bömmel F, "Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection", Hepatology, 40, pp.1421~1425 (2004)
  15. Schiff E, "Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis", Am J Gastroenterol, 103, pp.2776~2783 (2008)
  16. van Nunen AB, "Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase", Gut, 52, pp.420~424 (2003)
  17. 정영화, "Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea", HEPATOLOGY, 32, pp.803~806 (2000), JOHN WILEY & SONS INC
  18. Chang TT, "Durability of HBeAg seroconversion after adefovir dipivoxil treatment for chronic hepatitis B (CHB)", J Hepatol, 40(1), pp.126~ (2004)
  19. Chen CJ, "Long-term outcomes in hepatitis B: the REVEAL-HBV study", Clin Liver Dis, 11, pp.797~816 (2007)
  20. Zacharakis G, "The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(-) hepatitis B infection: association with liver disease progression. A prospective cohort study", J hepatol, 49, pp.884~891 (2008)
  21. Bortolotti F, "Chronic hepatitis B in children after e antigen seroclearance: final report of a 29-year longitudinal study", Hepatology, 43, pp.556~562 (2006)
  22. Chu CM, "Natural history of chronic hepatitis B virus infection in Taiwan: studies of hepatitis B virus DNA in serum", Hepatology, 5, pp.431~434 (1985)
  23. Hsu YS, "Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B", Hepatology, 35, pp.1522~1527 (2002)
  24. Dienstag JL, "Durability of serologic response after lamivudine treatment of chronic hepatitis B", Hepatology, 37, pp.748~755 (2003)
  25. Alexander G, "High rates of early HBeAg seroconversion and relapse in Indian patients of chronic hepatitis B treated with Lamivudine: results of an open labeled trial", BMC Gastroenterol, 5, pp.29~ (2005)

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