OBJECTIVETo 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.

METHODSA 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 (5×10(6), 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.

RESULTSAt 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).

CONCLUSIONChronic 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.