Adefovir plus lamivudine are more effective than adefovir alone in lamivudine-resistant HBeAg- chronic hepatitis B patients: A 4-year study

作者：Vassiliadis Themistoklis G; Giouleme Olga; Koumerkeridis Georgios; Koumaras Haralabos; Tziomalos Konstantinos^*; Patsiaoura Kalliopi; Grammatikos Nikolaos; Mpoumponaris Alexandros; Gkisakis Dimitrios; Theodoropoulos Konstantinos; Panderi Athanasia; Katsinelos Panagiotis; Eugenidis Nikolaos

来源：Journal of Gastroenterology and Hepatology, 2010, 25(1): 54-60.

DOI：10.1111/j.1440-1746.2009.05952.x

• adefovir dipivoxil
• adefovir resistance
• chronic hepatitis B
• combination therapy
• hepatitis B e antigen-negative
• chronic hepatitis B
• lamivudine
• lamivudine resistance

Background and Aim:
Adefovir dipivoxil (ADV) is effective in lamivudine (LAM)-resistant hepatitis B e antigen-negative (HBeAg-) chronic hepatitis B (CHB). However, it is unclear whether LAM treatment should be continued in these patients. We aimed to compare the long-term efficacy of adding ADV to ongoing LAM treatment versus switching to ADV monotherapy in LAM-resistant HBeAg- CHB.
Methods:
Sixty LAM-resistant patients with HBeAg- CHB were randomly assigned (3:1) to combination therapy (10 mg ADV once daily plus ongoing LAM at 100 mg once daily [n = 45]) or 10 mg ADV monotherapy once daily (n = 15). Virological and biochemical responses were defined as hepatitis B virus (HBV)-DNA < 400 copies/mL and as normalization of alanine aminotransferase levels, respectively.
Results:
The median follow-up time was 53 months (range 20-60 months). A virological response was observed in 38/45 (84.4%) and 11/15 (73.3%) patients in the ADV/LAM and ADV monotherapy groups, respectively (P = 0.56). Biochemical response rates were higher in the ADV/LAM group than in the ADV monotherapy group (90.9% vs 57.1%, respectively; P = 0.01). In the ADV/LAM group, serum HBV-DNA remained undetectable in all patients who achieved a virological response (n = 38). In the ADV monotherapy group, virological breakthrough occurred in four of the 11 patients who achieved a virological response (36.4%; P < 0.001 vs the ADV/LAM group, log-rank test). In addition, two patients in each group who did not achieve a virological response eventually developed ADV resistance.
Conclusions:
Adding ADV to LAM is more effective than switching to ADV monotherapy in LAM-resistant patients with HBeAg- CHB.

• 出版日期2010-1