Comparison of lamivudine plus adefovir therapy versus entecavir with or without adefovir therapy for adefovir-resistant chronic hepatitis B.
OBJECTIVE
Data regarding the management of adefovir (ADV) resistance are still limited. The aim of this study is to investigate treatment outcomes of rescue therapy in ADV-resistant chronic hepatitis B (CHB) patients.


METHODS
CHB patients who began rescue therapy due to documented genotypic resistance mutations to ADV between October 2006 and July 2012 were retrospectively reviewed.


RESULTS
Sixty-three patients were included in this study. Most patients had history of lamivudine (LAM) resistance. Treatment response was evaluated at 3-month intervals up to 12 months. The cumulative rate of complete virologic response (CVR) in hepatitis B virus (HBV)-infected patients (HBV DNA<60 IU/mL) was 15.9%, 27.2%, 28.9%, and 31.7% after 3, 6, 9, and 12 months of rescue therapy. Thirty-five patients were treated with a combination of LAM plus ADV (LAM+ADV group) and 28 patients were treated with entecavir (ETV)-based therapy (ETV with or without ADV therapy, ETV±ADV group). The cumulative CVR rate was significantly higher in the ETV±ADV group than in the LAM+ADV group at month 12 (46.4% vs. 20.6%, respectively, P=0.040). Multivariate analysis showed that pretreatment serum HBV DNA levels at <6 log10 IU/mL (hazard ratio: 34.109, P=0.001) and type of rescue therapy (hazard ratio: 4.944, P=0.036) were associated with CVR.


CONCLUSIONS
Lower baseline HBV DNA level and ETV±ADV therapy were the important predictive factors for CVR in ADV-resistant CHB patients. This study suggests the need of early switching to a rescue therapy such as ETV±ADV at the time of low-level viremia.
Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea.
Seong Hee
SH
Kang
Hyung Joon
HJ
Yim
Hae Rim
HR
Kim
Keunhee
K
Kang
Sang Jun
SJ
Suh
Hyun Jung
HJ
Lee
Eileen L
EL
Yoon
Ji Hoon
JH
Kim
Yeon Seok
YS
Seo
Jong Eun
JE
Yeon
Kwan Soo
KS
Byun
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; C053001:adefovir; D000225:Adenine