Aims:Little is known about the duration of combination therapy in optimization of chronic hepatitis B (CHB)patients with suboptimal response to nucleos(t)ide analogues(NAs).This study aimed to assess whether switching-to monotherapy could be considered for CHB patients,who responded poorly to adefovir dipivoxil(ADV) but obtained good responses after receiving at least 12 months of lamivudine(LAM) or telbivudine(LdT) add-on therapy.Methods:Forty-five eligible patients with LAM+ADV or LdT+ADV combination therapy were enrolled and prospectively followed,and baseline time-point was determined according to their enrollment data.Of them,26 patients continued combination therapy (Group A) and 19 patients switched to NAs monotherapy(LAM or LdT or ADV,Group B).Results:There were no significant differences between two groups in baseline characteristics (p>0.05).At 12 months,sustained virological response rate was significantly greater in group A than in group B(96.2% vs.47.4%,p<0.001); and alanine aminotransferase normalization rate was also significantly higher in group A than in group B(92.3% vs.36.8%,p<0.001).Among hepatitis B e antigen (HBeAg) positive patients,40%(4/10) in group A and 9.1%(1/11) in group B achieved HBeAg seroconversion at 12 months.Of patients in group B,both positive-HBeAg prior to previous combination therapy and detectable HBV DNA at 6 months of previous combination therapy were associated with high risks of viral relapse after switching to monotherapy.Conclusion:Prematurely switching to monotherapy would easily result to viral relapse,and prolonged combination therapy was efficacious to maintain sustained responses for patients with initial suboptimal response to ADV.