Prolonged Combination Therapy is More Effective than Monotherapy in Management of Chronic Hepatitis B Patients With Sustained Virological Response: An Experience From a ‘Real-World’ Clinical Setting

BACKGROUND Little is known about the duration of combination therapy for patients with chronic hepatitis B (CHB) and suboptimal response to nucleos(t)ide analogues(NAs) monotherapy. OBJECTIVES This study aimed to assess whether monotherapy could be used for treatment of CHB patients, who poorly responded to Adefovir Dipivoxil (ADV) but obtained good responses after at least 12-month lamivudine (LAM) or telbivudine (LdT) add-on therapy. PATIENTS AND METHODS Forty-five patients were enrolled, and the baseline time-point was determined according to enrollment data. Twenty-six patients chose to continue combination therapy (LAM+ADV or LdT+ADV, Group A) and 19 patients switched to single-drug maintenance therapy (LAM or LdT or ADV, Group B). RESULTS There were no significant differences between two groups in baseline characteristics (P > 0.05). At 12th month, sustained virological response rate was greater in group A compared to group B (96.2% vs. 47.4%, P < 0.001), and the rates of NAs-associated resistance were 0% in group A and 15.8% in group B. Alanine aminotransferase normalization rate was also significantly higher in group A compared with group B (92.3% vs. 36.8%, P < 0.001). Among hepatitis positive patients with Be antigen (HBeAg)-, 40% (4/10) in group A and 9.1% (1/11) in group B achieved HBeAg seroconversion at the 12th month. Of patients in group B with positive-HBeAg before the 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 single-drug maintenance therapy. CONCLUSIONS Prematurely switching to single-drug maintenance therapy would be resulted in viral relapse, and prolonged combination therapy was effective to maintain sustained responses for patients with initial suboptimal response to ADV.