Long-term outcomes of two rescue therapies in lamivudine- refractory patients with chronic hepatitis B: combined lamivudine and adefovir, and 1-mg entecavir
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Background/Aims: Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option forpatients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mgentecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomesof these two rescue therapies. Methods: Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). Wedetermined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV)DNA by PCR (lower limitation of detection, <140 copies/mL), biochemical response (alanine aminotransferase <40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. Results: Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P =0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%,respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough andresistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P =0.001). Conclusions: Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppressionand resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.
Abstract
Background/Aims: Adefovir (ADV) and lamivudine (LAM) combination therapy (ADV+LAM) has been a useful option forpatients with LAM-resistant (LAM-r) chronic hepatitis B (CHB). However, the long-term outcomes of LAM+ADV and 1-mgentecavir (ETV) rescue therapies have still been limited. The aim of this study was to determine the long-term outcomesof these two rescue therapies. Methods: Sixty patients with LAM-r CHB underwent rescue therapy with LAM+ADV (n=36) or 1-mg ETV (n=24). Wedetermined the duration of rescue therapy, timing and type of mutation, undetectable serum hepatitis B virus (HBV)DNA by PCR (lower limitation of detection, <140 copies/mL), biochemical response (alanine aminotransferase <40 IU/mL), and the incidence of hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. Results: Baseline characteristics did not differ between the two therapy groups. The duration of rescue therapy was 56months (range, 14-100 months) in the ADV+LAM group and 42 months (range, 12-73 months) in the ETV group (P =0.036). The cumulative rates of HBV DNA undetectability and HBeAg seroconversion up to 6 years were 88.6% and 43.0%,respectively, in the ADV+LAM group, and 45.8% and 31.8% in the ETV group. The rate of virologic breakthrough andresistance was 14.4% in the ADV+LAM group and 71.9% in the ETV group (P =0.001). Conclusions: Combination of LAM and ADV therapy for up to 6 years achieved modest rates of virological suppressionand resistance. ETV is not an optimal therapy because the risk of viral breakthrough to ETV increases over time.
참고문헌 (27)
- Chen CJ, "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level", JAMA, 295, pp.65~73 (2006)
- Iloeje UH, "Predicting cirrhosis risk based on the level of circulating hepatitis B viral load", Gastroenterology, 130, pp.678~686 (2006)
- Pawlotsky JM, "Virologic monitoring of hepatitis B virus therapy in clinical trials and practice: recommendations for a standardized approach", Gastroenterology, 134, pp.405~415 (2008)
- Lok AS, "Chronic hepatitis B", Hepatology, 45, pp.507~539 (2007)
- McMahon BJ., "Selecting appropriate management strategies for chronic hepatitis B: who to treat", Am J Gastroenterol, 101(Suppl 1), pp.S7~S12 (2006)
- Pramoolsinsup C., "Management of viral hepatitis B", J Gastroenterol Hepatol, 17(Suppl), pp.S125~S145 (2002)
- Lai CL, "Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial", Hepatology, 25, pp.241~244 (1997)
- Papatheodoridis GV, "Current treatment indications and strategies in chronic hepatitis B virus infection", World J Gastroenterol, 14, pp.6902~6910 (2008)
- Zoulim F., "Entecavir: a new treatment option for chronic hepatitis B", J Clin Virol, 36, pp.8~12 (2006)
- Perrillo R, "Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus", Gastroenterology, 126, pp.81~90 (2004)
- Tenney DJ, "Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy", Hepatology, 49, pp.1503~1514 (2009)
- Sheng YJ, "Lamivudine plus adefovir combination therapy versus entecavir monotherapy for lamivudine-resistant chronic hepatitis B: a systematic review and meta-analysis", Virol J, 8, pp.393~ (2011)
- 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)
- Chung GE, "Addon adefovir is superior to a switch to entecavir as rescue therapy for Lamivudine-resistant chronic hepatitis B", Dig Dis Sci, 56, pp.2130~2136 (2011)
- Ryu HJ, "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, 82, pp.1835~1842 (2010)
- Tenney DJ, "Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine", Antimicrob Agents Chemother, 48, pp.3498~3507 (2004)
- Villet S, "Stepwise process for the development of entecavir resistance in a chronic hepatitis B virus infected patient", J Hepatol, 46, pp.531~538 (2007)
- Baldick CJ, "Comprehensive evaluation of hepatitis B virus reverse transcriptase substitutions associated with entecavir resistance", Hepatology, 47, pp.1473~1482 (2008)
- Yeon JE, "Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil", Gut, 55, pp.1488~1495 (2006)
- 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)
- Peters MG, "Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B", Gastroenterology, 126, pp.91~101 (2004)
- Rapti I, "Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B", Hepatology, 45, pp.307~313 (2007)
- Yatsuji H, "Low risk of adefovir resistance in lamivudine-resistant chronic hepatitis B patients treated with adefovir plus lamivudine combination therapy: two-year follow-up", J Hepatol, 48, pp.923~931 (2008)
- Lampertico P, "Low resistance to adefovir combined with lamivudine: a 3-year study of 145 lamivudine-resistant hepatitis B patients", Gastroenterology, 133, pp.1445~1451 (2007)
- van Bömmel F1, "Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection", Hepatology, 40, pp.1421~1425 (2004)
- van Bömmel 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)
- van Bömmel F, "Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside", nucleotide analogues, 2010, pp.51, 73~80