HBV : Long-term Outcomes of Rescue Therapy between Entecavir 1 mg Therapy and Adefovir Combination Therapy in Lamivudine-Refractory Patients with Chronic Hepatitis B = HBV : Long-term Outcomes of Rescue Therapy between Entecavir 1 mg Therapy and Adefovir Combination Therapy in Lamivudine-Refractory Patients with Chronic Hepatitis B

다국어 초록 (Multilingual Abstract)

Background/Aims: There is a paucity of data on the longterm efficacy of combination lamivudine (LMV) plus adefovir (ADV) combination or entecavir (ETV) rescue therapy in patients with LMV-resistant chronic hepatitis B (LMV-r CHB). Methods: 51 patients with LMV-r CHB underwent rescue therapy with LAM [100 mg (qd)]+ADV [10 mg (qd)] (n=32, ADV combination group) and ETV [1mg(qd)] (n=19, ETV group). We determined the duration of rescue therapy, timing and type of mutation, undetectable serum HBV DNA by PCR (lower limitation of detection, <140 copies/mL), biochemical response (alanine aminotransferase (ALT) <40 IU/mL), and hepatitis B virus e antigen (HBeAg) seroconversion and virologic breakthrough. Results: Baseline characteristics were not different between the two groups. The duration of rescue therapy in ADV combination and ETV group was 55.7 months (range 22-91 months) vs 43.6 months (range 13-71 months)(P=0.036). The rate of sustained treatment was 62.5% vs. 31.6% (P=0.033). In ADV combination group, the cumulative rates of HBV-DNA undetectability, ALT normalization, and HBeAg seroconversion up to 5 years were 62.5%. 100%, and 33.3%, respectively. Three patients had genotypic resistance (A181T/S/V, median period, 12.7 months). In ETV group, five patients had genotypic resistance (S202I, T184G, median period, 22.8 months). The rates of virologic breakthrough in each group were 31.3%(10/32) vs 63.1%(13/19). The rates of cumulative virologic breakthrough at 12, 24, 36, 48, and 60 months in each group were 3%, 16%, 22%, 25%, and 28%, vs 16%, 26%, 47%, 58%, and 68%, respectively. Conclusions: Combination LAM plus ADV therapy for up to 5 years achieved modest rates of virological suppression, but resistance developed in only 9.4% of patients. ETV is not an optimal therapy because of increasing risk of viral breakthrough to ETV over time.