Z Gastroenterol 2008; 46 - P262
DOI: 10.1055/s-0028-1089637

Combination therapy with Adefovir and Entecavir is well tolerated and effective in Lamivudine-resistant chronic Hepatitis B

A Weinmann 1, A Grambihler 1, A Beckers 1, J Kittner 1, H Schulze-Bergkamen 1, M Wörns 1, T Bock 2, PR Galle 1, W Böcher 3, M Schuchmann 1
  • 1Klinikum der Johannes Gutenberg-Universität, I. Medizinische Klinik und Poliklinik, Mainz, Germany
  • 2Klinikum der Universität Tübingen, Abtlg. für Molekulare Pathologie, Tübingen, Germany
  • 3Boehringer Ingelheim, Biberach an der Riss, Germany

Methods: 26 patients (pts) (23 male/3 female, age 49.3 (27.7–72.2yrs) with chronic hepatitis B (13 pts HBeAg pos) who were pretreated with and resistant to lamivudine received combination therapy with entecavir 1mg and adefovir 10mg daily. 9 pts (33%) had cirrhosis, none of them decompensated (MELD score 9, (6–13)); The mean duration of lamivudine pretreatment was 23 months (2–122 mo). In 10 pts lamivudine had been stopped or changed to another treatment more than 24 wks before the start of this study. 8 (30%) were switched directly from lamivudine monotherapy (5 pts) or combination therapy with lamivudine and adefovir (3 pts) to combination therapy with entecavir and adefovir. Lamivudine resistance was determined by virological or biochemical non-response or break-through during lamivudine treatment. In addition, mutational analysis was performed; lamivudine resistance mutations were found in all patients and were an inclusion criterion. No adefovir resistance mutations were detectable.

Results: At the start of combination therapy ALT was normal in 12 pts (43%), 10 had elevated ALT (3 pts not tested). ALT levels ranged between 0.36–10.3 *ULN (mean 1.9 * ULN). HBV-DNA was 87–6.4 * 108 copies/ml (mean 5.2 * 107 copies/ml; TaqMan PCR). Follow-up data (HBV DNA, week 12–24) was available of 19 pts. After 12 to 24 wks 43% of patients had normal ALT values (range 0.38–4.78, mean 1.4 * ULN). In 6 pts HBV-DNA was below detection level (70 copies/ml, TaqMan PCR), in 7 pts viral load was detectable but reduced by at least 2 log, 3 pts showed no virological response. 1 patient was switched to another therapeutic regimen because of biochemical non-response (ALT >2*ULN after 24 wks), 1 patient was switched because of a viral load >103 after 24 wks. No major side effects were observed due to combination therapy with entecavir and adefovir for up to 1 year. None of the patients showed signs of progression or complications due to chronic liver disease or cirrhosis.

Conclusion: This study suggests that combination therapy with entecavir and adefovir is well tolerated and effective in lamivudine-resistant chronic hepatitis B and should thus be considered as a treatment option for those patients.