The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy.
OBJECTIVE
Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination.


METHODS
We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy.


RESULTS
The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy.


CONCLUSIONS
The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases.
Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
Jeong Han
JH
Kim
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea.
Sung Hyun
SH
Ahn
Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
Soon Young
SY
Ko
Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
Won Hyeok
WH
Choe
Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine, IBST, Konkuk University School of Medicine, Seoul, Korea.
Kyun-Hwan
KH
Kim
Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
So Young
SY
Kwon
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis / Q000378:metabolism; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D056910:Republic of Korea; D012189:Retrospective Studies; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine
Adefovir; Chronic Hepatitis B; Entecavir; Lamivudine; Resistance; Tenofovir