Comparative efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B: A systematic review and meta-analysis

Autoři: Mao-bing Chen aff001;  Hua Wang aff002;  Qi-han Zheng aff001;  Xu-wen Zheng aff001;  Jin-nuo Fan aff001;  Yun-long Ding aff003;  Jia-li Niu aff004
Působiště autorů: Department of Emergency, Wujin People Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, P. R. China aff001;  Department of ICU, Wujin People Hospital Affiliated with Jiangsu University and Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu, P. R. China aff002;  Department of Neurology, Jingjiang People Hospital, Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, P. R. China aff003;  Department of Clinical Pharmacy, JingJiang People Hospital, Seventh Affliated Hospital of Yangzhou University, Jingjiang, Jiangsu, P. R. China aff004
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224773



To compare the efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B.


The Web of Science, PubMed, Cochrane Library, EMBASE, Clinical Trials and China National Knowledge Infrastructure(CNKI) databases were electronically searched to collect randomized controlled trials (RCTs) regarding the comparison between tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) since the date of database inception to July 2019. Two researchers independently screened and evaluated the obtained studies and extracted the outcome indexes. RevMan 5.3 software was used for the meta-analysis.


Early on, tenofovir had a greater ability to inhibit the hepatitis B virus, I2 = 0% [RR = 1.08, 95% CI (1.03, 1.13), P<0.01] (96 weeks). Entecavir can normalize the ALT levels earlier, I2 = 0% [RR = 0.87, 95% CI (0.77, 0.98), P = 0.02] (48 weeks). However, there was no statistically significant difference between TDF and ETV at 144 weeks. Tenofovir was as effective as entecavir in terms of HBeAg clearance and HBeAg seroconversion, I2 = 0% [RR = 1.05, 95% CI (0.68, 1.62), P = 0.82]; I2 = 69% [RR = 0.93, 95% CI (0.54, 1.61), P = 0.80]. The difference in the incidence of elevated creatine kinase levels was not statistically significant I2 = 0% [RR = 0.66, 95% CI (0.27, 1.60), P = 0.35].


Tenofovir and entecavir were equally effective in the treatment of patients with nucleos(t)ide analogue-naive chronic hepatitis B. In addition, TDF has an advantage in the incidence of hepatocellular carcinoma. Additional RCTs and a large-sample prospective cohort study should be performed.

Klíčová slova:

Antimicrobial resistance – Antivirals – Hepatitis B – Hepatitis B virus – Hepatocellular carcinoma – Chronic hepatitis – Creatine


1. Peng CW, Jeng WJ. Understanding More About Hepatitis Flare in Chronic Hepatitis B Patients. Clin Gastroenterol Hepatol. 2019. Epub 2019/07/03. doi: 10.1016/j.cgh.2019.05.053 31265807.

2. Dakic Z, Duric P, Fabri M, O'May F. Validity of hepatitis B and hepatitis C case definitions. J Infect Public Health. 2019. Epub 2019/02/18. doi: 10.1016/j.jiph.2019.01.061 30772265.

3. Fanning GC, Zoulim F, Hou J, Bertoletti A. Therapeutic strategies for hepatitis B virus infection: towards a cure. Nat Rev Drug Discov. 2019. Epub 2019/08/29. doi: 10.1038/s41573-019-0037-0 31455905.

4. Thomas E, Baumert TF. Hepatitis B Virus-Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms. Semin Liver Dis. 2019. Epub 2019/07/03. doi: 10.1055/s-0039-1685518 31266064.

5. Vittal A, Ghany MG. WHO Guidelines for Prevention, Care and Treatment of Individuals Infected with HBV: A US Perspective. Clin Liver Dis. 2019; 23(3): 417–432. Epub 2019/07/04. doi: 10.1016/j.cld.2019.04.008 31266617.

6. Kim SU, Seo YS, Lee HA, Kim MN, Lee YR, Lee HW, et al. A multicenter study of entecavir vs. tenofovir on prognosis of treatment-naive chronic hepatitis B in South Korea. J Hepatol. 2019. Epub 2019/04/09. doi: 10.1016/j.jhep.2019.03.028 30959156.

7. Liem KS, Fung S, Wong DK, Yim C, Noureldin S, Chen J, et al. Limited sustained response after stopping nucleos(t)ide analogues in patients with chronic hepatitis B: results from a randomised controlled trial (Toronto STOP study). Gut. 2019. Epub 2019/08/30. doi: 10.1136/gutjnl-2019-318981 31462554.

8. Wong GL, Wong VW, Yuen BW, Tse YK, Luk HW, Yip TC, et al. An aging population of chronic hepatitis B with increasing co-morbidities—a territory-wide study from 2000 to 2017. Hepatology. 2019. Epub 2019/06/27. doi: 10.1002/hep.30833 31237366.

9. Luo J, You X, Chong Y, Wu Y, Gong J, Jie Y, et al. Efficacy of long-term treatment with tenofovir in Chinese nucleos(t)ide-naive chronic hepatitis B patients regardless of baseline viral load. Exp Ther Med. 2019; 18(1): 260–268. Epub 2019/07/02. doi: 10.3892/etm.2019.7547 31258661.

10. Sriprayoon T, Mahidol C, Ungtrakul T, Chun-On P, Soonklang K, Pongpun W, et al. Efficacy and safety of entecavir versus tenofovir treatment in chronic hepatitis B patients: A randomized controlled trial. Hepatol Res. 2017; 47(3): E161–E168. Epub 2016/05/14. doi: 10.1111/hepr.12743 27176630.

11. Koike K, Suyama K, Ito H, Itoh H, Sugiura W. Randomized prospective study showing the non-inferiority of tenofovir to entecavir in treatment-naive chronic hepatitis B patients. Hepatol Res. 2018; 48(1): 59–68. Epub 2017/04/05. doi: 10.1111/hepr.12902 28374496.

12. Cai D, Pan C, Yu W, Dang S, Li J, Wu S, et al. Comparison of the long-term efficacy of tenofovir and entecavir in nucleos(t)ide analogue-naive HBeAg-positive patients with chronic hepatitis B: A large, multicentre, randomized controlled trials. Medicine (Baltimore). 2019; 98(1): e13983. Epub 2019/01/05. doi: 10.1097/MD.0000000000013983 30608440.

13. Lin H-x. Clinical effect of tenofovir and entecavir in patients with HBeAg-positive initial Chronic Hepatitis B. Shandong Medicine. 2016; 56(33): 92–94.

14. Zhang D LS, Lu W, et al. Clinical efficacy of tenofovir and entecavir in the treatment of chronic hepatitis b infection in patients naïve to nucleosides and their analogues therapy. International Journal of Clinical and Experimental Medicine. 2017; 10(8): 12329–12335.

15. Wong GL, Chan HL, Tse YK, Yip TC, Lam KL, Lui GC, et al. Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B. J Hepatol. 2018; 69(4): 793–802. Epub 2018/05/15. doi: 10.1016/j.jhep.2018.05.009 29758335.

16. Wong GL, Seto WK, Wong VW, Yuen MF, Chan HL. Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B. Aliment Pharmacol Ther. 2018; 47(6): 730–737. Epub 2018/01/24. doi: 10.1111/apt.14497 29359487.

17. Downs LO, Smith DA, Lumley SF, Patel M, McNaughton AL, Mokaya J, et al. Electronic Health Informatics Data To Describe Clearance Dynamics of Hepatitis B Surface Antigen (HBsAg) and e Antigen (HBeAg) in Chronic Hepatitis B Virus Infection. MBio. 2019; 10(3). Epub 2019/06/27. doi: 10.1128/mBio.00699-19 31239374.

18. Tu T, Budzinska MA, Vondran FWR, Shackel NA, Urban S. Hepatitis B Virus DNA Integration Occurs Early in the Viral Life Cycle in an In Vitro Infection Model via Sodium Taurocholate Cotransporting Polypeptide-Dependent Uptake of Enveloped Virus Particles. J Virol. 2018; 92(11). Epub 2018/02/14. doi: 10.1128/JVI.02007-17 29437961.

19. Geipel A, Seiz PL, Niekamp H, Neumann-Fraune M, Zhang K, Kaiser R, et al. Entecavir allows an unexpectedly high residual replication of HBV mutants resistant to lamivudine. Antivir Ther. 2015; 20(8): 779–787. Epub 2015/01/07. doi: 10.3851/IMP2928 25560463.

20. Yang S, Wang L, Pan W, Bayer W, Thoens C, Heim K, et al. MMP2/MMP9-mediated CD100 shedding is crucial for inducing intrahepatic anti-HBV CD8 T cell responses and HBV clearance. J Hepatol. 2019. Epub 2019/06/08. doi: 10.1016/j.jhep.2019.05.013 31173811.

21. Liaw YF, Jeng WJ, Chang ML. HBsAg Kinetics in Retreatment Decision for Off-Therapy Hepatitis B Flare in HBeAg-Negative Patients. Gastroenterology. 2018; 154(8): 2280–2281. Epub 2018/05/11. doi: 10.1053/j.gastro.2018.03.066 29746811.

22. Ray G. 5-year efficacy of entecavir in Indian patients with chronic hepatitis B. Indian J Gastroenterol. 2016; 35(3): 190–194. Epub 2016/05/25. doi: 10.1007/s12664-016-0664-x 27216583.

23. Samuels R, Bayerri CR, Sayer JA, Price DA, Payne BAI. Tenofovir disoproxil fumarate-associated renal tubular dysfunction: noninvasive assessment of mitochondrial injury. AIDS. 2017; 31(9): 1297–1301. Epub 2017/03/23. doi: 10.1097/QAD.0000000000001466 28323756.

24. Zhang Z, Zhou Y, Yang J, Hu K, Huang Y. The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: a meta analysis. BMC Cancer. 2019; 19(1): 511. Epub 2019/05/31. doi: 10.1186/s12885-019-5735-9 31142283.

25. Li HM, Wang JQ, Wang R, Zhao Q, Li L, Zhang JP, et al. Hepatitis B virus genotypes and genome characteristics in China. World J Gastroenterol. 2015; 21(21): 6684–6697. Epub 2015/06/16. doi: 10.3748/wjg.v21.i21.6684 26074707.

Článek vyšel v časopise


2019 Číslo 11