Adefovir plus lamivudine are more effective than adefovir alone in lamivudine-resistant HBeAg- chronic hepatitis B patients: a 4-year study.
Author(s): Vassiliadis TG, Giouleme O, Koumerkeridis G, Koumaras H, Tziomalos K, Patsiaoura K, Grammatikos N, Mpoumponaris A, Gkisakis D, Theodoropoulos K, Panderi A, Katsinelos P, Eugenidis N
Affiliation(s): Gastroenterology and Hepatology Division, Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Publication date & source: 2010-01, J Gastroenterol Hepatol., 25(1):54-60. Epub 2009 Sep 22.
Publication type: Comparative Study; Randomized Controlled Trial
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.