The efficacy of adefovir dipivoxil monotherapy and the incidence of genotypic resistance to adefovir dipivoxil in patients with Lamivudine-resistant chronic hepatitis B infection

doi:2008.14.4.503

Korean J Hepatol > Volume 14(4); 2008 > Article

The Korean Journal of Hepatology 2008;14(4): 503-512.
doi: https://doi.org/10.3350/kjhep.2008.14.4.503

The efficacy of adefovir dipivoxil monotherapy and the incidence of genotypic resistance to adefovir dipivoxil in patients with Lamivudine-resistant chronic hepatitis B infection

Jae Hyeon Moon , Mong Cho , Ki Tae Yoon , Jung Ho Bae , Jeong Heo , Gwang Ha Kim , Dae Hwan Kang , Geun Am Song

Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea

ABSTRACT

Background/Aims
Adefovir dipivoxil (ADV) is a nucleotide analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine (LMV)-resistant HBV mutants. The aim of this study was to elucidate the efficacy of ADV monotherapy and the incidence of genotypic resistance to ADV in patients with LMV-resistant chronic HBV infection. Methods: This study involved 124 patients with chronic HBV infection who had received ADV monotherapy due to the presence of LMV-resistant HBV mutants. The efficacy of ADV was evaluated by the normalization of serum alanine aminotransferase (ALT) level and by the reduction of serum HBV DNA level (with cutoff levels of 2×10⁴ IU/mL and 2×10² IU/mL). The cumulative rate of HBeAg loss or seroconversion was assessed in HBeAg-positive patients. The development of mutations in the reverse trancriptase region of HBV DNA polymerase was evaluated by direct sequencing analysis during ADV monotherapy. Results: The mean serum HBV DNA level was 5.94 log10IU/mL. At 12 and 24 months after ADV monotherapy, the cumulative rates of serum ALT normalization were 69.4% and 75.5%, respectively, and those of serum HBV DNA reduction were 79.8% and 89.2% for a cutoff level of 2×10⁴ IU/mL, and 44.2% and 59.0% for a cutoff of 2×10² IU/mL. The mean serum HBV DNA levels at 12 and 24 months were significantly lower than baseline, at 3.24 and 3.04 log10IU/mL, respectively (P<0.001). At 12 months after ADV treatment, the cumulative rates of HBeAg loss and seroconversion were 15.8% and 10.5%, respectively, and the rtN236T and rtA181T/V mutants in HBV DNA polymerase were identified in 25% and 64% of patients, respectively. Conclusions: Although ADV monotherapy is effective, it leads to a high rate of mutations of HBV DNA reverse transcriptase gene in patients with chronic HBV infections who have LMV-resistant HBV mutants. (Korean J Hepatol 2008;14:503-512)

KeyWords: Chronic hepatitis B; Lamivudine; Adefovir; HBV reverse transcriptase; Resistance