title: Tenofovir monotherapy versus tenofovir plus lamivudine or telbivudine combination therapy in treatment of lamivudine-resistant chronic hepatitis B.
abstract: Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P=0.562 and P=0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors.forename: Yun Bin
authors.initials: YB
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Eun Uk
authors.initials: EU
authors.lastname: Jung
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea pindra@empal.com.
authors.forename: Jeong-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyeki
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hongkeun
authors.initials: H
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Won-Mook
authors.initials: WM
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Youn
authors.initials: YY
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Minjong
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jeong-Ju
authors.initials: JJ
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Su Jong
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Youn Jae
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Center for Liver Cancer, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chung Yong
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyo-Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine