Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results

Hepatology International - Tập 13 - Trang 260-269 - 2019
Xieer Liang1, Zhiliang Gao2, Qing Xie3, Jiming Zhang4, Jifang Sheng5, Jun Cheng6, Chengwei Chen7, Qing Mao8, Wei Zhao9, Hong Ren10, Deming Tan11, Junqi Niu12, Shijun Chen13, Chen Pan14, Hong Tang15, Hao Wang16, Yimin Mao17, Jidong Jia18, Qin Ning19, Min Xu20, Shanming Wu21, Jun Li22, Xinxin Zhang3, Wenyan Zhang23, Cui Xiong23, Jinlin Hou1
1State 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, China
23rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
3Ruijin Hospital Affiliated to Jiaotong University, School of Medicine, Shanghai, China
4Huashan Hospital affiliated to Fudan University, Shanghai, China
51st Affiliated Hospital of ZheJiang University, Hangzhou, China
6Beijing Ditan Hospital, Capital Medical University, Beijing, China
7Shanghai the 85th Hospital Affiliated to Nanjing Military, Shanghai, China
8Southwest Hospital, Army Medical University, Chongqing, China
92nd Hospital of Nanjing, Nanjing, China
102nd Affiliated Hospital Chongqing Medical University, Chongqing, China
11Xiangya Hospital, Central South University, Changsha, China
121st Affiliated Hospital of Jilin University, Changchun, China
13Jinan Hospital for Infectious Disease, Jinan, China
14Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian Sheng, China
15West China Hospital, Sichuan University, Chengdu, China
16Peking University People’s Hospital, Beijing, China
17Renji Hospital Shanghai, Jiaotong University School of Medicine, Shanghai, China;
18Beijing Friendship Hospital, Capital University, Beijing, China
19Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
20Guangzhou Eighth Municipal People’s Hospital, Guangzhou, China
21Shanghai Public Health Clinical Center, Shanghai, China
22The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
23GlaxoSmithKline R&D Company Limited, Shanghai, China

Tóm tắt

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. 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. 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). 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.

Tài liệu tham khảo

World Health Organization. Hepatitis B Fact Sheet. Geneva: WHO; 2017. http://www.who.int/mediacentre/factsheets/fs204/en/#. Accessed 23 Aug 2018 Buti M, Tsai N, Petersen J, et al. Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection. Dig Dis Sci 2015;60:1457–1464 Hou JL, Gao ZL, Xie Q, et al. Tenofovir disoproxil fumarate vs adefovir dipivoxil in Chinese patients with chronic hepatitis B after 48 weeks: a randomized controlled trial. J Viral Hepat 2015;22:85–93 Yang HI, Yuen MF, Chan HL, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol 2011;12:568–574 Marcellin P, Heathcote EJ, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008;359:2442–2455 Marcellin P, Gane E, Buti M et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 2013;381:468─475 Marcellin P, Buti M, Krastev Z, et al. Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate. J Hepatol 2014;61:1228–1237 Liang X, Xie Q, Tan D, et al. Interpretation of liver stiffness measurement-based approach for the monitoring of hepatitis B patients with antiviral therapy: a 2-year prospective study. J Viral Hepat 2018;25:296–305 Kim MN, Kim SU, Kim BK, et al. Long-term changes of liver stiffness values assessed using transient elastography in patients with chronic hepatitis B receiving entecavir. Liver Int 2014;34:1216–1223 Hezode C, Castera L, Roudot-Thoraval F, et al. Liver stiffness diminishes with antiviral response in chronic hepatitis C. Aliment Pharmacol Ther 2011;34:656–663 Liu Y, Corsa AC, Buti M, et al. No detectable resistance to tenofovir disoproxil fumarate in HBeAg+ and HBeAg− patients with chronic hepatitis B after 8 years of treatment. J Viral Hepat 2017;24:68–74 Gordon SC, Krastev Z, Horban A, et al. Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load. Hepatology 2013;58:505–513 Fung S, Gordon SC, Krastev Z, et al. Tenofovir disoproxil fumarate in Asian or Pacific Islander chronic hepatitis B patients with high viral load (>/= 9 log10 copies/ml). Liver Int 2015;35:422–428 Gish RG, Clark MD, Kane SD, Shaw RE, Mangahas MF, Baqai S. Similar risk of renal events among patients treated with tenofovir or entecavir for chronic hepatitis B. Clin Gastroenterol Hepatol 2012;10:941–946 Marcellin P, Zoulim F, Hezode C, et al. Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: a 3-year, prospective, real-world study in France. Dig Dis Sci 2016;61:3072–3083 Petersen J, Heyne R, Mauss S, et al. Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: a 3-year prospective field practice study in Germany. Dig Dis Sci 2016;61:3061–3071 Riveiro-Barciela M, Tabernero D, Calleja JL, et al. Effectiveness and safety of entecavir or tenofovir in a Spanish cohort of chronic hepatitis B patients: validation of the page-B score to predict hepatocellular carcinoma. Dig Dis Sci 2017;62:784–793 Agarwal K, Brunetto M, Seto WK, et al. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol 2018;68:672–681 Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016;1:196–206
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Hepatology International

Tập 13

260-269

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