Conclusions: The expression levels of IL-35 in PBMCs were significantly higher in CHB patients in immune-clearance phase than that in immune-tolerant phase. Increased IL-35 expression levels were associated with liver injury. Background: There are a number of oral antivirals approved for chronic hepatitis B. Lamivudine, the first oral nucleoside analog, is associated with increased rates of drug resistance with prolonged use--from 20% at one year to 50% at three years. Therefore, an alternative or add-on treatment is necessary. Adefovir, an oral nucleotide analog, is used either in combination with lamuvudine or as monotherapy in lamivudine-resistant chronic hepatitis B. We did a meta-analysis to compare the efficacy of adefovir in combination with lamivudine versus adefovir alone in the treatment of lamivudine-resistant chronic hepatitis B infection. Methods: A comprehensive literature search was performed using the following databases: Medline, Cochrane, and Embase. A total of 3 randomized controlled trials were retrieved and analyzed. Outcomes measured were virologic response, biochemical response and resistance rates. Results: Meta-analysis on virologic response showed that combination treatment with adefovir and lamivudine is as effective as adefovir monotherapy (OR 1.04, 95% CI 0.50-2.15, P=0.92). Likewise, in terms of biochemical response, both regimens were equally effective (OR 1.06, 95% CI 0.47-2.40, P=0.90). One study showed statistically significant increase in adefovir resistance rate in the monotherapy arm compared to combination arm (P= 0.0182) after the first year of therapy. Conclusion: In patients with lamivudine-resistant chronic hepatitis B infection and compensated liver disease, adding adefovir to lamivudine is as effective as switching to adefovir alone in terms of virologic and biochemical response.