Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir
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Background/Aims: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV. Methods: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV. Results: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001). Conclusions: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.
Abstract
Background/Aims: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV. Methods: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV. Results: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001). Conclusions: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.
참고문헌 (28)
- Triolo M, "Impact of HBV therapy on the incidence of hepatocellular carcinoma", Liver Int, 34(Suppl 1), pp.139~145 (2014)
- 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)
- Chang TT, "Long-term entecavir therapy results in the reversal of fibrosis", cirrhosis and continued histological improvement in patients with chronic hepatitis B, 2010, pp.52, 886~893
- Marcellin P, "Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study", Lancet, 381, pp.468~475 (2013)
- Hosaka T, "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection", Hepatology, 58, pp.98~107 (2013)
- Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
- Lok AS, "Long-term safety of lamivudine treatment in patients with chronic hepatitis B", Gastroenterology, 125, pp.1714~1722 (2003)
- Liaw YF, "Asian-pacific consensus statement on the management of chronic hepatitis B: a 2008 update", Hepatol Int, 2, pp.263~283 (2008)
- Lok AS, "Chronic hepatitis B", Hepatology, 45, pp.507~539 (2007)
- Tenney DJ, "Long-term monitoring shows hepatitis b virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy", Hepatology, 49, pp.1503~1514 (2009)
- Yuen MF, "Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy", Hepatology, 34(4), pp.785~791 (2001)
- Ghany MG, "Antiviral resistance and hepatitis B therapy", Hepatology, 49(5 Suppl), pp.S174~S184 (2009)
- European Association For The Study Of The Liver, "Easl clinical practice guidelines: Management of chronic hepatitis B virus infection", J Hepatol, 57, pp.167~185 (2012)
- Lok AS, "Chronic hepatitis B: update 2009", Hepatology, 50, pp.661~662 (2009)
- 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)
- Kim YJ, "Tenofovir rescue therapy for chronic hepatitis B patients after multiple treatment failures", World J Gastroenterol, 18, pp.6996~7002 (2012)
- Yip B, "Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy for entecavir partial responders", Dig Dis Sci, 57, pp.3011~3016 (2012)
- Wong CR, "High rate of complete viral suppression with combination therapy in patients with chronic hepatitis B and prior treatment failure", J Clin Gastroenterol, 45, pp.900~905 (2011)
- Petersen J, "Entecavir plus tenofovir combination as rescue therapy in pretreated chronic hepatitis B patients: an international multicenter cohort study", J Hepatol, 56, pp.520~526 (2012)
- Lim YS, "Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial", Gut, 65, pp.852~860 (2016)
- Lee S, "Tenofovir versus tenofovir plus entecavir for chronic hepatitis B with lamivudine resistance and entecavir resistance", J Viral Hepat, 24, pp.141~147 (2017)
- Yim HJ, "Evolution of multi-drug resistant hepatitis B virus during sequential therapy", Hepatology, 44, pp.703~712 (2006)
- Kim BG, "Tenofovirbased rescue therapy for chronic hepatitis B patients who had failed treatment with lamivudine, adefovir, and entecavir", J Gastroenterol Hepatol, 30, pp.1514~1521 (2015)
- Zoutendijk R, "Entecavir treatment for chronic hepatitis B: adaptation is not needed for the majority of naïve patients with a partial virological response", Hepatology, 54, pp.443~451 (2011)
- Yuen MF, "Three years of continuous entecavir therapy in treatment-naïve chronic hepatitis B patients: VIRAL suppression, viral resistance, and clinical safety", Am J Gastroenterol, 106, pp.1264~1271 (2011)
- Ono A, "Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients", J Hepatol, 57, pp.508~514 (2012)
- Shin JW, "Prediction of response to entecavir therapy in patients with HBeAgpositive chronic hepatitis B based on on-treatment HBsAg, HBeAg and HBV DNA levels", J Viral Hepat, 19, pp.724~731 (2012)