Finite Versus Continuous Nucleos(t)Ide Analogues for Chronic Hepatitis B

Summary

BACKGROUND: Finite nucleos(t)ide analogue (Nuc) therapy was proposed as an alternative strategy in the management of chronic hepatitis B (CHB) but there remained not data from randomized controlled trials to clarify safety and efficacy of this treatment strategy. AIMS: The investigators aimed to evaluate the safety and efficacy of finite Nuc therapy versus continuous treatment in CHB patients without liver cirrhosis and also to identify factors that may predict therapeutic responses and clinical outcomes after withdrawal of Nuc treatment for CHB MATERIAL AND METHODS: This is a multicenter randomized controlled trial conducted in Taiwan. Eligible patients are adults (age≥20 years) with CHB (chronic infection ≥ 6 months) who fulfill the APASL guideline 2016 to stop NA therapy. Those with cirrhosis, malignancy, organ transplant, autoimmune disorder, or serious underlying diseases including renal impairment were excluded. A total of 360 patients will be enrolled. Enrolled patients are randomly allocated with a 1:1 ratio to continue viral suppression with entecavir (0.5mg once daily) or tenofovir disoproxil fumarate (300mg once daily) or stop the treatment. All patients will be followed up according to the protocol recommended by a panel of APASL experts. The primary analysis for study outcomes is scheduled at 3 years after randomization and the primary outcome is seroclearance of HBsAg. There will be interim analyses scheduled at one- and two-years following randomization of the first 200 patients, and also one-and two years following randomization of the planned 360 patients, to determine whether early termination of the trial may be justified by attainment of the efficacy endpoint (10% vs 1% of HBsAg seroclearance) or concerns of the safety outcomes (significant between-group difference in mortality, acute on chronic liver failure, or acute flares with hepatic decompensation).

Timeline

Start

2022-12-20

Primary completion

2025-12

Completion

2026-12

Publications

• Background Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
• Background Kao JH, Jeng WJ, Ning Q, Su TH, Tseng TC, Ueno Y, Yuen MF. APASL guidance on stopping nucleos(t)ide analogues in chronic hepatitis B patients. Hepatol Int. 2021 Aug;15(4):833-851. doi: 10.1007/s12072-021-10223-5. Epub 2021 Jul 23.
• Background Hsu YC, Yeh ML, Wong GL, Chen CH, Peng CY, Buti M, Enomoto M, Xie Q, Trinh H, Preda C, Liu L, Cheung KS, Yeo YH, Hoang J, Huang CF, Riveiro-Barciela M, Kozuka R, Istratescu D, Tsai PC, Accarino EV, Lee DH, Wu JL, Huang JF, Dai CY, Cheung R, Chuang WL, Yuen MF, Wong VW, Yu ML, Nguyen MH. Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B. J Infect Dis. 2021 Dec 1;224(11):1890-1899. doi: 10.1093/infdis/jiab241.
• Background Berg T, Simon KG, Mauss S, Schott E, Heyne R, Klass DM, Eisenbach C, Welzel TM, Zachoval R, Felten G, Schulze-Zur-Wiesch J, Cornberg M, Op den Brouw ML, Jump B, Reiser H, Gallo L, Warger T, Petersen J; FINITE CHB study investigators [First investigation in stopping TDF treatment after long-term virological suppression in HBeAg-negative chronic hepatitis B]. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study. J Hepatol. 2017 Nov;67(5):918-924. doi: 10.1016/j.jhep.2017.07.012. Epub 2017 Jul 21.
• Background Jeng WJ, Chen YC, Chien RN, Sheen IS, Liaw YF. Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B. Hepatology. 2018 Aug;68(2):425-434. doi: 10.1002/hep.29640. Epub 2018 May 6.
• Background Hall SAL, Vogrin S, Wawryk O, Burns GS, Visvanathan K, Sundararajan V, Thompson A. Discontinuation of nucleot(s)ide analogue therapy in HBeAg-negative chronic hepatitis B: a meta-analysis. Gut. 2022 Aug;71(8):1629-1641. doi: 10.1136/gutjnl-2020-323979. Epub 2021 Sep 7.

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