한빛사 논문
Young-Suk Lim1,a,*, Geum-Youn Gwak2,a, Jonggi Choi1, Yung Sang Lee1, Kwan Soo Byun3, Yoon Jun Kim4, Byung Chul Yoo5, So Young Kwon5, Han Chu Lee1,*
1 Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3 Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
4 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
5 Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
aYS Lim and GY Gwak contributed equally to this article and deserve co-first authorship.
*Corresponding authors
Abstract
Background and Aims
Tenofovir disoproxil fumarate (TDF) monotherapy has displayed non-inferior efficacy compared with TDF plus entecavir (ETV) combination therapy in patients with hepatitis B virus (HBV) resistant to ETV and/or adefovir (ADV). Nonetheless, the virologic response rate was suboptimal up to 144 weeks of TDF monotherapy with uncertain long-term safety.
Methods
One trial enrolled patients with ETV resistance without ADV resistance (n=90), and another trial included patients with ADV resistance (n=102). Most patients (91.2%) also had LAM resistance. Patients were randomized 1:1 to receive TDF monotherapy or TDF+ETV combination therapy for 48 weeks, and then TDF monotherapy until 240 weeks. We compared efficacy between the studies and safety in the pooled population at 240 weeks.
Results
At week 240, the proportion of patients with serum HBV DNA <15 IU/mL was not significantly different between the ETV and ADV resistance groups in the full analysis set (84.4% vs. 73.5%; P=0.07), which was significantly different by on-treatment analysis (92.7% vs. 79.8%; P=0.02). Virologic blips associated with poor medication adherence occurred in 7 patients throughout the 240 weeks. None developed additional HBV resistance mutations. Among the 170 HBeAg-positive patients at baseline, 12 (7.1%) achieved HBeAg seroconversion at week 240. None achieved HBsAg seroclearance. Significant decreases from baseline were observed at week 240 in the estimated glomerular filtration rate (−3.21 mL/min/1.73 m2 by the CKD-EPI equation, P<0.001) and bone mineral density (g/cm2) at the femur (−2.48%, P<0.001).
Conclusions
TDF monotherapy provided an increasing virologic response rate for up to 240 weeks in heavily pretreated patients with HBV resistant to ETV and/or ADV. However, it was associated with poor serological responses and decreasing renal function and bone mineral density.
Lay summary
In patients chronically infected with hepatitis B virus resistant to multiple drugs including lamivudine, entecavir, and/or adefovir, tenofovir disoproxil fumarate (TDF) monotherapy showed non-inferior efficacy compared with the combination therapy with TDF plus entecavir. Nonetheless, short-term TDF monotherapy was associated with suboptimal virologic response, and its long-term safety was uncertain. This study displayed that 240 weeks of TDF monotherapy provided a virologic response in most of those patients, but was associated with poor serological responses and decreasing renal function and bone mineral density.
Keywords : Adefovir dipivoxil; Entecavir; Hepatitis B virus; Lamivudine; Resistance
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기