Hepatol Int. 2019 Apr 11. doi: 10.1007/s12072-019-09943-6. [Epub ahead of print]
Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results.
Liang X1, Gao Z2, Xie Q3, Zhang J4, Sheng J5, Cheng J6, Chen C7, Mao Q8, Zhao W9, Ren H10, Tan D11, Niu J12, Chen S13, Pan C14, Tang H15, Wang H16, Mao Y17, Jia J18, Ning Q19, Xu M20, Wu S21, Li J22, Zhang X3, Zhang W23, Xiong C23, Hou J24.
Author information
1
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
2
3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
3
Ruijin Hospital Affiliated to Jiaotong University, School of Medicine, Shanghai, China.
4
Huashan Hospital Affiliated to Fudan University, Shanghai, China.
5
1st Affiliated Hospital of ZheJiang University, Hangzhou, China.
6
Beijing Ditan Hospital, Capital Medical University, Beijing, China.
7
Shanghai the 85th Hospital Affiliated to Nanjing Military, Shanghai, China.
8
Southwest Hospital, Army Medical University, Chongqing, China.
9
2nd Hospital of Nanjing, Nanjing, China.
10
2nd Affiliated Hospital Chongqing Medical University, Chongqing, China.
11
Xiangya Hospital Central-South University, Changsha, China.
12
1st Affiliated Hospital of Jilin University, Changchun, China.
13
Jinan Hospital for Infectious Disease, Jinan, China.
14
Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian Sheng, China.
15
West China Hospital, Sichuan University, Chengdu, China.
16
Peking University People's Hospital, Beijing, China.
17
RenJi Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
18
Beijing Friendship Hospital, Capital University, Beijing, China.
19
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
20
Guangzhou Eighth Municipal People's Hospital, Guangzhou, China.
21
Shanghai Public Health Clinical Center, Shanghai, China.
22
The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
23
GlaxoSmithKline R&D Company Limited, Shanghai, China.
24
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Hepatology Unit and Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. [email protected].
Abstract
BACKGROUND AND AIM:
Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection.
METHODS:
Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF-TDF and ADV-TDF groups) for additional 192 weeks.
RESULTS:
Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF-TDF and ADV-TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF-TDF than in ADV-TDF group, respectively. Only one HBeAg-positive patient in TDF-TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF-TDF, 56.4% vs. ADV-TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL).
CONCLUSION:
In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.
KEYWORDS: