라미부딘 내성 만성 B형간염 환자에서 아데포비어 투여에 따른 내성 바이러스 출현 및 초기 바이러스반응에 미치는 인자
Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background/Aims: Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients. Methods: This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction- fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants. Results: After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01). Conclusions: Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant.
Abstract
Background/Aims: Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients. Methods: This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction- fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants. Results: After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01). Conclusions: Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant.
참고문헌 (21)
- Lok ASF, "AASLD Practice Guidelines: chronic hepatitis B", Hepatology, 45, pp.507~539 (2007)
- Lai CL, "Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B", Clin Infect Dis, 36, pp.687~696 (2003)
- Lok ASF, "Long-term safety of lamivudine treatment in patients with chronic hepatitis B", Gastroenterology, 125, pp.1714~1722 (2003)
- Peters MG, "Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine- resistant chronic hepatitis B", Gastroenterology, 126, pp.91~101 (2004)
- Lee YS, "Increased risk of adefovir resistance in patients with lamivudine-resistant chronic hepatitis B after 48weeks of adefovir dipivoxil monotherapy", Hepatology, 43, pp.1385~1391 (2006)
- Ryu SH, "Resistance to adefovir in patients with chronic hepatitis B", Korean J Hepatol, 12, pp.485~492 (2006)
- "Hepatology", 2005, 754A~
- Yeon JE, "Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil", Gut, 55, pp.1488~1495 (2006)
- Yuen MF, "Factors associated with hepatitis B virus DNA breakthough in patients receiving prolonged lamivudine therapy", Hepatology, 34, pp.785~791 (2001)
- Fung SK, "Virologic response and resistance to adefovir in patients with chronic hepatitis B", J Hepatol, 44, pp.283~290 (2006)
- Hong SP, "Detection of hepatitis B virus YMDD variants using mass spectrometric analysis of oligonucleotide fragments", J Hepatol, 40, pp.837~844 (2004)
- 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)
- Hadziyannis SJ, "Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B", N Engl J Med, 348, pp.800~807 (2003)
- Zeng M, "A double-blind randomized trial of adefovir dipivoxil in Chinese subjects with HBeAg-positive chronic hepatitis B", Hepatology, 44, pp.108~116 (2006)
- van Bömmel F, "Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection", Hepatology, 40, pp.1421~1425 (2004)
- "J Hepatol", 2006, 174~
- Chang TT, "Hepatitis B virus with primary resistance to adefovir", N Engl J Med, 355, pp.322~323 (2006)
- Rapti I, "Adding-on versus switching-to adefovir therapy in lamivudine- resistant HBeAg-negative chronic hepatitis B", Hepatology, 45, pp.307~313 (2007)
- Kim DY, "Efficacy of adefovir dipivoxil in the treatment of lamivudine-resistant hepatitis B virus genotype C infection", Liver Int, 27, pp.47~53 (2007)
- "J Hepatol", 2005, 36A~
- Perrillo R, "Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus", Gastroenterology, 126, pp.81~90 (2004)