BACKGROUND AND AIMS: The aim of this study was to determine the optimal time and HBV DNA levels during the treatment period for prediction of virological breakthrough (VBT) 3 years after adefovir monotherapy in chronic hepatitis B (CHB) patients with lamivudine resistance. METHODS: We consecutively analyzed HBV DNA levels within 12 months in 210 lamivudine-resistant CHB patients treated with adefovir monotherapy for more than 36 months. RESULTS: VBT, genotypic adefovir mutations, and virologic responses were observed in 52 (24.8%), 37 (17.6%), and 117 (55.7%) cases within 3 years of treatment, respectively. Using receiver-operating characteristic curve analysis, HBV DNA levels at month 12 had a greater power (AUROC, 0.839; 95% CI, 0.759-0.919; p<0.001) to predict VBT after 3 years of treatment. The best cut-off value of HBV DNA levels at month 12 for predicting VBT at 3 years of treatment was 200 IU/ml with a sensitivity and negative predictive value of 88.5 and 94.3%, respectively. Using this time and cut-off value, VBT had developed in six (5.7%) of the patients with HBV DNA levels<200 IU/ml (n=105) and 46 (43.8%) of the patients with HBV DNA levels≥200 IU/ml (n=105) at month 12 (p<0.001). Moreover, virological response or HBeAg seroconversion remained higher at 82.9 and 81.2%, respectively. CONCLUSIONS: In patients who were switched to adefovir monotherapy as rescue therapy for lamivudine resistance before the introduction of current therapeutic guidelines, measurements of HBV DNA levels at month 12 should be performed to predict VBT. Early termination of adefovir monotherapy should be considered for patients who still have HBV DNA≥200 IU/ml (3 log10 copies/ml) at 12 months of treatment.
BACKGROUND AND AIMS: The aim of this study was to determine the optimal time and HBV DNA levels during the treatment period for prediction of virological breakthrough (VBT) 3 years after adefovir monotherapy in chronic hepatitis B (CHB) patients with lamivudine resistance. METHODS: We consecutively analyzed HBV DNA levels within 12 months in 210 lamivudine-resistant CHB patients treated with adefovir monotherapy for more than 36 months. RESULTS: VBT, genotypic adefovir mutations, and virologic responses were observed in 52 (24.8%), 37 (17.6%), and 117 (55.7%) cases within 3 years of treatment, respectively. Using receiver-operating characteristic curve analysis, HBV DNA levels at month 12 had a greater power (AUROC, 0.839; 95% CI, 0.759-0.919; p<0.001) to predict VBT after 3 years of treatment. The best cut-off value of HBV DNA levels at month 12 for predicting VBT at 3 years of treatment was 200 IU/ml with a sensitivity and negative predictive value of 88.5 and 94.3%, respectively. Using this time and cut-off value, VBT had developed in six (5.7%) of the patients with HBV DNA levels<200 IU/ml (n=105) and 46 (43.8%) of the patients with HBV DNA levels≥200 IU/ml (n=105) at month 12 (p<0.001). Moreover, virological response or HBeAg seroconversion remained higher at 82.9 and 81.2%, respectively. CONCLUSIONS: In patients who were switched to adefovir monotherapy as rescue therapy for lamivudine resistance before the introduction of current therapeutic guidelines, measurements of HBV DNA levels at month 12 should be performed to predict VBT. Early termination of adefovir monotherapy should be considered for patients who still have HBV DNA≥200 IU/ml (3 log10 copies/ml) at 12 months of treatment.
Authors: Yoon-Seon Lee; Dong Jin Suh; Young-Suk Lim; Suk Won Jung; Kang Mo Kim; Han Chu Lee; Young-Hwa Chung; Yung Sang Lee; Wangdon Yoo; Soo-Ok Kim Journal: Hepatology Date: 2006-06 Impact factor: 17.425
Authors: Stephanos J Hadziyannis; Nicolaos C Tassopoulos; E Jenny Heathcote; Ting-Tsung Chang; George Kitis; Mario Rizzetto; Patrick Marcellin; Seng Gee Lim; Zachary Goodman; Jia Ma; Sarah Arterburn; Shelly Xiong; Graeme Currie; Carol L Brosgart Journal: N Engl J Med Date: 2005-06-30 Impact factor: 91.245
Authors: Christopher E Westland; Huiling Yang; William E Delaney; Craig S Gibbs; Michael D Miller; Michael Wulfsohn; John Fry; Carol L Brosgart; Shelly Xiong Journal: Hepatology Date: 2003-07 Impact factor: 17.425
Authors: Robert Perrillo; Hie-Won Hann; David Mutimer; Bernard Willems; Nancy Leung; William M Lee; Alison Moorat; Stephen Gardner; Mary Woessner; Eric Bourne; Carol L Brosgart; Eugene Schiff Journal: Gastroenterology Date: 2004-01 Impact factor: 22.682
Authors: Marion G Peters; H w Hann Hw; Paul Martin; E Jenny Heathcote; P Buggisch; R Rubin; M Bourliere; K Kowdley; C Trepo; D f Gray Df; M Sullivan; K Kleber; R Ebrahimi; S Xiong; Carol L Brosgart Journal: Gastroenterology Date: 2004-01 Impact factor: 22.682