Abstract: Objective To compare the efficacy and safety of recombinant human interferon α-2b (INFα-2b) monotherapy and
combined therapy with entecavir (ETV) plus adefovir dipivoxil (ADV) in chronic hepatitis B patients with poor response to
combined therapy with lamivudine and ADV. Methods A total of 161 patients with chronic hepatitis B refractory to to
combined therapy with lamivudine (LAM) and ADV were randomized to receive INFα-2b monotherapy (5×106, three times a
week) (group A) or combined therapy with entecavir (0.5 mg/day) plus adefovir (10 mg/day) (group B). Serum levels of
HBsAg, HBeAg and HBV viral load were analyzed at 48 weeks using chemiluminescence assay and by real-time PCR as
appropriate. The drug resistance genes in HBV was tested by direct DNA sequencing. Results At 48 weeks of treatment, HBV
DNA decreased significantly in groups A and B to 2.06±1.15log10 copies/ml and 1.77±1.28log10 copies/ml, respectively. The
rates of viral response, serological response, and biochemical response in groups A and B were 48.15% (39/81) vs 53.75% (43/
80), 61.70% (50/81) vs 53.75% (43/80), and 49.38% (40/81) vs 60.00% (48/80), showing no significant differences between the two
groups (P>0.05). The drug resistance gene mutation rate was significanty higher in group B (64.86%, 24/37) than in group A
(30.95%, 13/42, P<0.05). Conclusions Chronic hepatitis B patients refractory to lamivudine combined with ADV have a good
response to INFα-2b monotherapy and combined therapy with entecavir and ADV , and interferon treatment is preferred to
reduce potential drug resistance gene mutations.