Is the tenofovir based therapy almighty for previous treatment failure in chronic hepatitis B?

During the past decade, management of drug resistant chronic hepatitis B (CHB) has been a major issue. A series of new antiviral agents has been developed, which provided new treatment options as well as new resistance issues. Hence, to avoid multidrug resistance, combination of antiviral agents without cross resistance has been recommended. However, combination of the less potent drug did not produce a better efficacy while the incidence of additional resistance has decreased. A more potent drug was needed for a better antiviral response. Tenofovir disproxil fumarate (TDF) is a nucleotide analogue which has a strong antiviral effect in treatment naïve as well as treatment experienced CHB patients for a long term periods. Also its therapeutic efficacy is much improved than that of adefovir (ADV). Therefore it is natural that combination therapy containing TDF show higher response rates than ADV-based therapies for management of drug resistance. Previously, TDF plus ETV therapy was evaluated in Western countries, and subsequently in Korea as well (Table 1). This combination therapy showed a better virologic response compared with ADV plus ETV therapy in refractory or suboptimal responders to lamivudine (LMV) plus ADV combination in a retrospective study conducted in Korea (at 12 month, 84.8% vs. 26.7%, respectively, P<0.001). The study included 58.7% of multidrug resistant CHB patients. Single arm studies of TDF-ETV combination were reported with a retrospective and a prospective design in Korea. Virologic response was achieved in approximately 80% of patients within a year. Furthermore, the antiviral efficacy was not influenced by the type of prior therapies and baseline resistance mutations in both studies. 9,10 In the current issue, Kim et al. introduced an interesting data regarding management of suboptimal responders to ETV-ADV combination therapy. They observed the patients for a long term period up to 3 years after initiating ETV-ADV combination therapy for LMV, ADV, and/or ETV resistance. In addition, the authors evaluated the responses of TDF based therapy which was introduced in case of refractory to the ETV-ADV combination. Among 48 patients enrolled, 12 patients achieved virologic response within 3 years, and 26 patients switched to the TDF based therapies due to suboptimal response despite long term ETV-ADV combination therapy. Ten patients received TDF monotherapy, of whom 9 achieved virologic response while 9 patients received TDF combination therapy (TDF-LMV in 7 and TDF-ETV combination in 2 patients), of whom 8 achieved virologic response. The authors subsequently performed in vitro susceptibility test using replicons See Article on Page 241 Is the tenofovir based therapy almighty for previous treatment failure in chronic hepatitis B?