Tenofovir vs. Tenofovir Plus Entecavir in Entecavir-Resistant Chronic Hepatitis B

With the availability of potent nucloes(t)ide analogues (NA), such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV), suppression of serum HBV DNA to undetectable levels by polymerase chain reaction (PCR) assays became achievable in most NA treatment-naïve patients. Until recently, however, many patients commenced antiviral treatment with inferior NAs prior to the availability of TDF or ETV, such as lamivudine (LAM) which has a low genetic barrier to resistance. ETV resistance increase up to 51% of patients after 5 years of ETV treatment in lamivudine-refractory patients. Resistance to ETV appears to occur through a two-hit mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at rtT184, rtS202, or rtM250. In vitro studies showed that ETV-resistant mutations are susceptible to TDF, but there are little clinical data on the efficacy of TDF monotherapy in patients with ETV-resistance. On the other hand, there was a retrospective cohort study reporting that, with the combination of TDF and ETV, most of patients became HBV DNA undetectable after median 6 months of treatment. Probability of reaching complete HBV DNA suppression was not decreased in patients with ADV or ETV-resistance. Thus, there is no consistent treatment recommendation for patients with ETV-resistance. In this clinical trial, the investigators will clarify whether tenofovir monotherapy is as effective as tenofovir plus entecavir in inducing complete virologic response in CHB patients with genotypic resistance to ETV and partial virologic response to ongoing treatment.