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High rates of progressive hepatic functional deterioration whether lamivudine therapy is continued or discontinued after emergence of a lamivudine-resistant mutant: a prospective randomized controlled study

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Abstract

Background

The management of patients with lamivudine-resistant mutants remains challenging, and no clear evidence has been presented concerning the discontinuation of lamivudine.

Methods

Seventy-four patients with lamivudine-resistant mutants were prospectively enrolled and randomized; 37 patients continued (group A) and 37 patients discontinued lamivudine therapy (group B). The median follow-up was 20 months.

Results

Serum albumin levels were reduced and prothrombin time was prolonged in both groups versus baseline (P = 0.015 and 0.045, respectively). Four patients in group A (10.8%) and six in group B (16.2%) experienced hepatitis flare, but the difference was not significant (P > 0.05). Multivariate analyses identified a younger age as a risk factor for hepatitis flare (P = 0.021). Seven (18.9%) decompensations occurred in group A and five (13.5%) in group B, which was not a significant difference (P > 0.05). Multivariate analyses revealed higher alanine aminotransferase and a lower platelet count as risk factors for hepatic decompensation (P = 0.001 and 0.001, respectively). The patients whose platelet count was <65 000/μl experienced hepatic decompensations more frequently (50%) than those with platelet counts >65 000/μl (13.2%) during follow-up (P = 0.05).

Conclusions

The clinical course of group B was not significantly different from that of group A. Therefore, the discontinuation of lamivudine may be a feasible option when other antiviral agents active against lamivudine-resistant mutants are unavailable.

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References

  1. WM Lee (1997) ArticleTitleHepatitis B virus infection N Engl J Med 337 1733–45 Occurrence Handle10.1056/NEJM199712113372406 Occurrence Handle1:STN:280:DyaK1c%2FktFyjtA%3D%3D Occurrence Handle9392700

    Article  CAS  PubMed  Google Scholar 

  2. C Niederau T Heintges S Lange G Goldmann CM Niederau L Mohr et al. (1996) ArticleTitleLong-term follow-up of HBeAg-positive patients treated with interferon alpha for chronic hepatitis B N Engl J Med 334 1422–7 Occurrence Handle10.1056/NEJM199605303342202 Occurrence Handle1:STN:280:BymB3Mfot1E%3D Occurrence Handle8618580

    Article  CAS  PubMed  Google Scholar 

  3. JL Dienstag RD Goldin EJ Heathcote HW Hann M Woessner SL Stephenson et al. (2003) ArticleTitleHistological outcome during long-term lamivudine therapy Gastroenterology 124 105–17 Occurrence Handle10.1053/gast.2003.50013 Occurrence Handle1:CAS:528:DC%2BD3sXot1antQ%3D%3D Occurrence Handle12512035

    Article  CAS  PubMed  Google Scholar 

  4. InstitutionalAuthorNameConsensus statements on the prevention and management of hepatitis B and hepatitis C in the Asia-Pacific region (2000) ArticleTitleCore Working Party for Asia-Pacific Consensus on Hepatitis B and C J Gastroenterol Hepatol 15 825–41 Occurrence Handle10.1046/j.1440-1746.2000.02324.x

    Article  Google Scholar 

  5. AS Lok BJ McMahon (2001) ArticleTitleChronic hepatitis B Hepatology 34 1225–41 Occurrence Handle10.1053/jhep.2001.29401 Occurrence Handle1:STN:280:DC%2BD3MnosV2qtw%3D%3D Occurrence Handle11732013

    Article  CAS  PubMed  Google Scholar 

  6. M Melegari PP Scaglioni JR Wands (1998) ArticleTitleHepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective Hepatology 27 628–33 Occurrence Handle10.1002/hep.510270243 Occurrence Handle1:CAS:528:DyaK1cXhtVGgurw%3D Occurrence Handle9462667

    Article  CAS  PubMed  Google Scholar 

  7. YF Liaw RN Chien CT Yeh SL Tsai CM Chu (1999) ArticleTitleAcute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy Hepatology 30 567–72 Occurrence Handle10.1002/hep.510300221 Occurrence Handle1:CAS:528:DyaK1MXlt1ajsLg%3D Occurrence Handle10421670

    Article  CAS  PubMed  Google Scholar 

  8. YF Liaw (2001) ArticleTitleImpact of YMDD mutations during lamivudine therapy in patients with chronic hepatitis B Antivir Chem Chemother 12 Suppl 1 67–71 Occurrence Handle1:STN:280:DC%2BD3MrkvVWisw%3D%3D Occurrence Handle11594691

    CAS  PubMed  Google Scholar 

  9. JW Kim HS Lee GH Woo JH Yoon JJ Jang JG Chi et al. (2001) ArticleTitleFatal submassive hepatic necrosis associated with tyrosine-methionine-aspartate-aspartate-motif mutation of hepatitis B virus after long-term lamivudine therapy Clin Infect Dis 33 403–5 Occurrence Handle10.1086/321879 Occurrence Handle1:STN:280:DC%2BD3MzosVCrtQ%3D%3D Occurrence Handle11438912

    Article  CAS  PubMed  Google Scholar 

  10. P Honkoop RA de Man HG Niesters PE Zondervan SW Schalm (2000) ArticleTitleAcute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy Hepatology 32 635–9 Occurrence Handle10.1053/jhep.2000.16333 Occurrence Handle1:CAS:528:DC%2BD3cXmsF2mu7k%3D Occurrence Handle10960461

    Article  CAS  PubMed  Google Scholar 

  11. YF Liaw RN Chien CT Yeh (2004) ArticleTitleNo benefit to continue lamivudine therapy after emergence of YMDD mutations Antivir Ther 9 257–62 Occurrence Handle1:CAS:528:DC%2BD2cXltFyhs7g%3D Occurrence Handle15134188

    CAS  PubMed  Google Scholar 

  12. VW Wong HL Chan ML Wong JS Tam NW Leung (2004) ArticleTitleClinical course after stopping lamivudine in chronic hepatitis B patients with lamivudine-resistant mutants Aliment Pharmacol Ther 19 323–9 Occurrence Handle10.1111/j.1365-2036.2004.01845.x Occurrence Handle1:CAS:528:DC%2BD2cXisVWhsrg%3D Occurrence Handle14984379

    Article  CAS  PubMed  Google Scholar 

  13. RN Pugh IM Murray-Lyon JL Dawson MC Pietroni R Williams (1973) ArticleTitleTransection of the oesophagus for bleeding oesophageal varices Br J Surg 60 646–9 Occurrence Handle1:STN:280:CSyB3svhvFU%3D Occurrence Handle4541913

    CAS  PubMed  Google Scholar 

  14. SP Hong NK Kim SG Hwang HJ Chung S Kim JH Han et al. (2004) ArticleTitleDetection of hepatitis B virus YMDD variants using mass spectrometric analysis of oligonucleotide fragments J Hepatol 40 837–44 Occurrence Handle10.1016/j.jhep.2004.01.006 Occurrence Handle1:CAS:528:DC%2BD2cXjtFOiurc%3D Occurrence Handle15094233

    Article  CAS  PubMed  Google Scholar 

  15. CL Lai J Dienstag E Schiff NW Leung M Atkins C Hunt et al. (2003) ArticleTitlePrevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B Clin Infect Dis 36 687–96 Occurrence Handle10.1086/368083 Occurrence Handle1:CAS:528:DC%2BD3sXjtVKqtbk%3D Occurrence Handle12627352

    Article  CAS  PubMed  Google Scholar 

  16. DT Lau MF Khokhar E Doo MG Ghany D Herion Y Park et al. (2000) ArticleTitleLong-term therapy of chronic hepatitis B with lamivudine Hepatology 32 828–34 Occurrence Handle10.1053/jhep.2000.17912 Occurrence Handle1:CAS:528:DC%2BD3cXnslemsbY%3D Occurrence Handle11003630

    Article  CAS  PubMed  Google Scholar 

  17. S Nafa S Ahmed D Tavan C Pichoud F Berby L Stuyver et al. (2000) ArticleTitleEarly detection of viral resistance by determination of hepatitis B virus polymerase mutations in patients treated by lamivudine for chronic hepatitis B Hepatology 32 1078–88 Occurrence Handle10.1053/jhep.2000.19619 Occurrence Handle1:STN:280:DC%2BD3M%2FivFagsQ%3D%3D Occurrence Handle11050059

    Article  CAS  PubMed  Google Scholar 

  18. SJ Hadziyannis GV Papatheodoridis E Dimou A Laras C Papaioannou (2000) ArticleTitleEfficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B Hepatology 32 847–51 Occurrence Handle10.1053/jhep.2000.17915 Occurrence Handle1:CAS:528:DC%2BD3cXnslemtr4%3D Occurrence Handle11003633

    Article  CAS  PubMed  Google Scholar 

  19. GV Papatheodoridis E Dimou A Laras V Papadimitropoulos SJ Hadziyannis (2002) ArticleTitleCourse of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease Hepatology 36 219–26 Occurrence Handle10.1053/jhep.2002.33894 Occurrence Handle12085368

    Article  PubMed  Google Scholar 

  20. NW Leung CL Lai TT Chang R Guan CM Lee KY Ng et al. (2001) ArticleTitleExtended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy Hepatology 33 1527–32 Occurrence Handle10.1053/jhep.2001.25084 Occurrence Handle1:CAS:528:DC%2BD3MXktlygtLc%3D Occurrence Handle11391543

    Article  CAS  PubMed  Google Scholar 

  21. MF Yuen T Kato M Mizokami AO Chan JC Yuen HJ Yuan et al. (2003) ArticleTitleClinical outcome and virologic profiles of severe hepatitis B exacerbation due to YMDD mutations J Hepatol 39 850–5 Occurrence Handle10.1016/S0168-8278(03)00388-X Occurrence Handle1:CAS:528:DC%2BD3sXotVert7k%3D Occurrence Handle14568270

    Article  CAS  PubMed  Google Scholar 

  22. RA de Man AI Bartholomeusz HG Niesters PE Zondervan SA Locarnini (1998) ArticleTitleThe sequential occurrence of viral mutations in a liver transplant recipient re-infected with hepatitis B: hepatitis B immune globulin escape, famciclovir non-response, followed by lamivudine resistance resulting in graft loss J Hepatol 29 669–75 Occurrence Handle10.1016/S0168-8278(98)80164-5 Occurrence Handle1:STN:280:DyaK1M%2FjvFyrtg%3D%3D Occurrence Handle9824278

    Article  CAS  PubMed  Google Scholar 

  23. AH Malik WM Lee (1999) ArticleTitleHepatitis B therapy the plot thickens Hepatology 30 579–81 Occurrence Handle10.1002/hep.510300238 Occurrence Handle1:STN:280:DyaK1MzltVCjsA%3D%3D Occurrence Handle10421673

    Article  CAS  PubMed  Google Scholar 

  24. N Shimada K Yamamoto MJ Kuroda R Terada T Hakoda H Shimomura et al. (2003) ArticleTitleHBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells J Clin Immunol 23 223–32 Occurrence Handle10.1023/A:1023366013858 Occurrence Handle1:CAS:528:DC%2BD3sXivVCks7w%3D Occurrence Handle12797544

    Article  CAS  PubMed  Google Scholar 

  25. R Perrillo HW Hann D Mutimer B Willems N Leung WM Lee et al. (2004) ArticleTitleAdefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus Gastroenterology 126 81–90 Occurrence Handle10.1053/j.gastro.2003.10.050 Occurrence Handle1:CAS:528:DC%2BD2cXhtFGntL0%3D Occurrence Handle14699490

    Article  CAS  PubMed  Google Scholar 

  26. MG Peters H Hann Hw P Martin EJ Heathcote P Buggisch R Rubin et al. (2004) ArticleTitleAdefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B Gastroenterology 126 91–101 Occurrence Handle10.1053/j.gastro.2003.10.051 Occurrence Handle1:CAS:528:DC%2BD2cXhtFGntLo%3D Occurrence Handle14699491

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Chongno-gu, Seoul, 110-744, Korea

    Yoon Jun Kim, Byeong Gwan Kim, Jun-Oh Jung, Jung-Hwan Yoon & Hyo-Suk Lee

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  1. Yoon Jun Kim
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  2. Byeong Gwan Kim
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  3. Jun-Oh Jung
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  4. Jung-Hwan Yoon
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  5. Hyo-Suk Lee
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Kim, Y., Kim, B., Jung, JO. et al. High rates of progressive hepatic functional deterioration whether lamivudine therapy is continued or discontinued after emergence of a lamivudine-resistant mutant: a prospective randomized controlled study. J Gastroenterol 41, 240–249 (2006). https://doi.org/10.1007/s00535-005-1750-5

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  • DOI: https://doi.org/10.1007/s00535-005-1750-5

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