ウイルス学および抗ウイルス研究ジャーナル

Adefovir plus Entecavir Therapy in Chronic Hepatitis B Patients with Treatment Failure to Lamivudine-Entecavir Sequential Therapy: Outcome at 2 Years

Jong Won Choi, Se Hyun Kim, Jeong Hun Suh, Yong Suk Cho, Sun Young Won, Byung Kyu Park, Han Ho Cheon and Chun Kyon Lee

The efficacy of adefovir add-on therapy in treatmentexperienced patients with chronic hepatitis B (CHB) is debatable. This study aimed to evaluate the efficacy of adefovir add-on therapy in CHB patients with antiviral resistance to lamivudine/entecavir sequential therapy. CHB patients who exhibited documented resistance to lamivudine and switched to entecavir 1.0 mg monotherapy were evaluated and 19 of them showed active viral replication (HBV DNA levels ≥ 10⁵ copies/mL) or a history of treatment failure to lamivudine/ entecavir sequential therapy. Adefovir 10 mg/day has been added to these 19 patients and the virologic parameters were monitored every three months for 96 weeks. A primary responder was defined as patient who had a decline in serum HBV DNA ≥ 1 log10 copies/mL after 12 weeks of therapy, compared with the pretreatment value. In 19 CHB patients, 10(52.6%) patients were HBeAg positive, 7 (36.8%) had cirrhosis. The mean duration of previous entecavir therapy was 84.4 ± 22.5 weeks. The mean HBV DNA levels and ALT at baseline were 6.17 ± 0.96 log10 copies/mL, 53 ± 35 IU/L. The reduction of serum HBV DNA levels from baseline was 2.27 ± 1.34, 2.77 ± 1.41, and 3.09 ± 1.37 log10 copies/mL, at 24, 48 and 96 weeks, respectively. The rate of undetectable serum HBV DNA was 10.5% (2/19), 26.3% (5/19), and 31.5% (6/19) and ALT levels were normalized in 5 (55.6%), 6(66.7%), and 6(66.7%) of 9 patients with elevated ALT at baseline. Initial HBV DNA level was the only independent factor that was inversely associated with serum HBV DNA negativity at 96 weeks. Among 7 primary non-responders, 6 patients achieved serum HBV-DNA level < 4 log10 copies/mL at 96 weeks. Until 96 weeks, viral breakthrough was not detected in 19 patients. The adefovir add-on therapy may be helpful, even if not sufficient enough, for CHB patients with antiviral resistance to lamivudine/entecavir sequential therapy.