Tenofovir vs. Tenofovir Plus Entecavir in Entecavir-Resistant Chronic Hepatitis B
Status:
Completed
Trial end date:
2018-03-29
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 4
Details
Lead Sponsor:
Asan Medical Center
Collaborators:
Konkuk University Medical Center Korea University Guro Hospital Samsung Medical Center Seoul National University Hospital