Is Combination Antiviral Therapy Mandatory for Maintenance Therapy in Fully Suppressed Multidrug-Resistant Hepatitis B Patients?

AIM: The efficacy of tenofovir disoproxil fumarate (TDF) monotherapy as maintenance therapy in multidrug-resistant (MDR) hepatitis B virus (HBV) patients after complete virologic suppression (CVS) has not been well evaluated. We evaluated the efficacy of maintenance TDF monotherapy compared with conventional TDF plus entecavir combination therapy after CVS of MDR HBV. METHODS: In this single-center retrospective study, patients with MDR HBV who were previously treated with entecavir plus TDF combination therapy and achieved CVS were included. Patients were either maintained on entecavir plus TDF combination therapy or switched to TDF monotherapy after CVS. The primary endpoint was the virologic breakthrough, and secondary outcomes were liver cirrhosis (LC) or hepatocellular carcinoma (HCC) development. To overcome immortal time bias, time-varying Cox proportional hazard regression analysis was performed. RESULTS: A total of 201 patients were included, and 153 patients were maintained on entecavir plus TDF combination therapy (combination group); 48 patients were converted from combination therapy to TDF monotherapy (single group) after CVS. Five patients experienced a virologic breakthrough, one patient in the single group owing to poor transient compliance and four patients in the combination group (P = 0.51). One new case of LC developed in the single group; five cases of LC developed in the combination group (P = 0.35). No new HCC development occurred in the single group, while seven cases of HCC developments were noted in the combination group. However, these results were not statistically significant (P = 0.54). CONCLUSIONS: For patients with suppressed HBV DNA, the efficacy of TDF monotherapy as maintenance therapy is comparable to that of entecavir plus TDF combination therapy.