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Original Article | Open Access

Clinical outcomes of cessation of nucleoside/nucleotide analogues in Chinese patients with HBeAg-negative chronic hepatitis B

Fengyi Lia,1, Yadong Zhangb,1, Chao Liua,1, Juan Lia( ), Dali Zhanga( ), Yinjie Gaoa( )
Senior Department of Hepatology, the Fifth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
Health Center of Armed Police Supervision, Daxing District, Beijing 102607, China

1 Fengyi Li, Yadong Zhang, and Chao Liu contributed equally to this work.

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Abstract

Background and aims

Cessation of nucleoside/nucleotide analogue (Nuc) therapy in patients with HBeAg-negative chronic hepatitis B (CHB) remains controversial.

Methods

In this prospective, single-center cohort study, we recruited 45 patients with HBeAg-negative CHB from The Fifth Medical Center of Chinese People's Liberation Army General Hospital in mainland China. Patients were classified into a Nuc cessation group (n = 27) and Nuc continuation group (n = 18) and followed-up for 36 months. Nuc were stopped after being inactive for at least 4 years (normal alanine aminotransferase (ALT), undetectable hepatitis B virus (HBV) DNA), with liver fibrosis ≤ Stage1 (S1) and inflammation ≤ Grade (G1).

Results

Within 3 years of follow-up, 51.9% patients with Nuc cessation had virological relapse and 14.8% had ALT elevation, while all patients with Nuc continuation had undetectable HBV DNA and normal ALT. The rate of HBsAg loss after Nuc cessation was 22.2% compared with no seroconversion in patients with Nuc continuation. The hepatitis flare rate was 11.1% and there were no cases of hepatic decompensation after Nuc cessation. End of treatment (EOT) HBsAg, HBV RNA, and decline in HBV core-related antigen (HBcrAg) rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.

Conclusion

This study showed favorable HBsAg loss and low hepatitis flare rates after Nuc cessation. EOT HBsAg, HBV RNA, and decline in HBcrAg rate were predictive markers for HBsAg seroconversion at 6 months post-Nuc cessation.

Keywords

Nucleoside analoguesNucleotide analoguesTherapy cessationHBeAg-negativeClinical relapse

References

[1]

Ott JJ, Stevens GA, Groeger J, et al. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine 2012;30(12):2212-9. https://doi.org/10.1016/j.vaccine.2011.12.116.
Crossref Google Scholar
[2]

Tang LSY, Covert E, Wilson E, et al. Chronic hepatitis B infection: a review. JAMA 2018;319(17):1802-13. https://doi.org/10.1001/jama.2018.3795.
Crossref Google Scholar
[3]

Kim GA, Lim YS, An J, et al. HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability. Gut 2014;63(8):1325-32. https://doi.org/10.1136/gutjnl-2013-305517.
Crossref Google Scholar
[4]

Yip TCF, Wong GLH, Wong VWS, et al. Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients. J Hepatol 2017:S0168-S8278(17)32332-2. https://doi.org/10.1016/j.jhep.2017.09.018.
Crossref Google Scholar
[5]

Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016;10(1):1-98. https://doi.org/10.1007/s12072-015-9675-4.
Crossref Google Scholar
[6]

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu, European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;67(2):370–98. https://doi.org/10.1016/j.jhep.2017.03.021.
Crossref Google Scholar
[7]

Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018;67(4):1560-99. https://doi.org/10.1002/hep.29800.
Crossref Google Scholar
[8]

Chang ML, Liaw YF, Hadziyannis SJ. Systematic review: cessation of long-term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen-negative chronic hepatitis B. Aliment Pharmacol Ther 2015;42(3):243-57. https://doi.org/10.1111/apt.13272.
Crossref Google Scholar
[9]

Hadziyannis SJ, Sevastianos V, Rapti I, et al. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology 2012;143(3):629-636.e1. https://doi.org/10.1053/j.gastro.2012.05.039.
Crossref Google Scholar
[10]

Berg T, Simon KG, Mauss S, et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients - FINITE study. J Hepatol 2017;67(5):918-24. https://doi.org/10.1016/j.jhep.2017.07.012.
Crossref Google Scholar
[11]

Jeng WJ, Chen YC, Chien RN, et al. 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;68(2):425-34. https://doi.org/10.1002/hep.29640.
Crossref Google Scholar
[12]

Chen CH, Hung CH, Wang JH, et al. The incidence of hepatitis B surface antigen loss between hepatitis B E antigen-negative noncirrhotic patients who discontinued or continued entecavir therapy. J Infect Dis 2019;219(10):1624-33. https://doi.org/10.1093/infdis/jiy697.
Crossref Google Scholar
[13]

Liaw YF. Finite nucleos(t)ide analog therapy in HBeAg-negative chronic hepatitis B: an emerging paradigm shift. Hepatol Int 2019;13(6):665-73. https://doi.org/10.1007/s12072-019-09989-6.
Crossref Google Scholar
[14]

Seto WK, Hui AJ, Wong VWS, et al. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut 2015;64(4):667-72. https://doi.org/10.1136/gutjnl-2014-307237.
Crossref Google Scholar
[15]

Chang ML, Liaw YF. Hepatitis B flares in chronic hepatitis B: pathogenesis, natural course, and management. J Hepatol 2014;61(6):1407-17. https://doi.org/10.1016/j.jhep.2014.08.033.
Crossref Google Scholar
[16]

Jeng WJ, Chen YC, Sheen IS, et al. Clinical relapse after cessation of tenofovir therapy inHepatitis B e antigen-negative patients. Clin Gastroenterol Hepatol 2016;14(12):1813-18120.e1. https://doi.org/10.1016/j.cgh.2016.07.002.
Crossref Google Scholar
[17]

Liaw YF. Hepatitis B flare after cessation of Nucleos(t)ide analogue therapy in HBeAg-Negative chronic hepatitis B: to retreat or not to retreat. Hepatology 2021;73(2):843-52. https://doi.org/10.1002/hep.31525.
Crossref Google Scholar
[18]

Liem KS, Fung S, Wong DK, 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;68(12):2206-13. https://doi.org/10.1136/gutjnl-2019-318981.
Crossref Google Scholar
[19]

Wong GLH, Chan HLY, Yiu KKL, et al. Meta-analysis: the association of hepatitis B virus genotypes and hepatocellular carcinoma. Aliment Pharmacol Ther 2013;37(5):517-26. https://doi.org/10.1111/apt.12207.
Crossref Google Scholar
[20]

Chen CJ, Yang HI. Natural history of chronic hepatitis B REVEALed. J Gastroenterol Hepatol 2011;26(4):628-38. https://doi.org/10.1111/j.1440-1746.2011.06695.x.
Crossref Google Scholar
[21]

Liem KS, Gehring AJ, Feld JJ, et al. Challenges with stopping Long-term Nucleos(t)ide analogue therapy in patients with chronic hepatitis B. Gastroenterology 2020;158(5):1185-90. https://doi.org/10.1053/j.gastro.2019.10.050.
Crossref Google Scholar
[22]

Chen CH, Hung CH, Hu TH, et al. Association between level of hepatitis B surface antigen and relapse after entecavir therapy for chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2015;13(11):1984–19892.e1. https://doi.org/10.1016/j.cgh.2015.06.002.
Crossref Google Scholar
[23]

Xie Y, Li M, Ou X, et al. HBeAg-positive patients with HBsAg < 100 IU/mL and negative HBV RNA have lower risk of virological relapse after nucleos(t)ide analogues cessation. J Gastroenterol 2021;56(9):856-67. https://doi.org/10.1007/s535-021-01812-0.
Crossref Google Scholar
[24]

Liu J, Li T, Zhang L, et al. The role of hepatitis B surface antigen in Nucleos(t)ide analogues cessation among Asian patients with chronic hepatitis B: a systematic review. Hepatology 2019;70(3):1045-55. https://doi.org/10.1002/hep.30474.
Crossref Google Scholar
[25]

Wang J, Shen T, Huang X, et al. Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound. J Hepatol 2016;65(4):700-10. https://doi.org/10.1016/j.jhep.2016.05.029.
Crossref Google Scholar
[26]

Fan R, Zhou B, Xu M, et al. Association between negative results from tests for HBV DNA and RNA and durability of response after discontinuation of Nucles(t)ide analogue therapy. Clin Gastroenterol Hepatol 2020;18(3):719–727.e7. https://doi.org/10.1016/j.cgh.2019.07.046.
Crossref Google Scholar
[27]

Mak LY, Wong DKH, Cheung KS, et al. Review article: hepatitis B core-related antigen (HBcrAg):an emerging marker for chronic hepatitis B virus infection. Aliment Pharmacol Ther 2018;47(1):43-54. https://doi.org/10.1111/apt.14376.
Crossref Google Scholar
[28]

Liu Y, Xue J, Liao W, et al. Serum HBV RNA dynamic and drug withdrawal predictor value in patients with chronic HBV infection on Long-term Nucleos(t)ide analogue (na) therapy. J Clin Gastroenterol 2020;54(8):e73-e82. https://doi.org/10.1097/MCG.0000000000001376.
Crossref Google Scholar
[29]

Tsuge M, Murakami E, Imamura M, et al. Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients. J Gastroenterol 2013;48(10):1188-204. https://doi.org/10.1007/s535-012-0737-2.
Crossref Google Scholar
[30]

Mak LY, Seto WK, Fung J, et al. Use of HBsAg quantification in the natural history and treatment of chronic hepatitis B. Hepatol Int 2020;14(1):35-46. https://doi.org/10.1007/s12072-019-09998-5.
Crossref Google Scholar
[31]

Dunn C, Brunetto M, Reynolds G, et al. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med 2007;204(3):667-80. https://doi.org/10.1084/jem.20061287.
Crossref Google Scholar
[32]

Maini MK, Boni C, Lee CK, et al. The role of virus-specific CD8+ cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 2000;191(8):1269-80. https://doi.org/10.1084/jem.191.8.1269.
Crossref Google Scholar
[33]

Tan AT, Koh S, Goh W, et al. A longitudinal analysis of innate and adaptive immune profile during hepatic flares in chronic hepatitis B. J Hepatol 2010;52(3):330-9. https://doi.org/10.1016/j.jhep.2009.12.015.
Crossref Google Scholar
[34]

Rivino L, Le Bert N, Gill US, et al. Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. J Clin Invest 2018;128(2):668-81. https://doi.org/10.1172/JCI92812.
Crossref Google Scholar
[35]

Rinker F, Zimmer CL, Höner Zu Siederdissen C, et al. Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B. J Hepatol 2018;69(3):584-93. https://doi.org/10.1016/j.jhep.2018.05.004.
Crossref Google Scholar
[36]

Zimmer CL, Rinker F, Höner zu Siederdissen C, et al. Increased NK cell function after cessation of Long-Term Nucleos(t)ide analogue treatment in chronic hepatitis B is associated with liver damage and HBsAg loss. J Infect Dis 2018;217(10):1656-66. https://doi.org/10.1093/infdis/jiy097.
Crossref Google Scholar
iLIVER
Volume 3 Issue 2,
June 2024
Article number: 100093
DOI: 10.1016/j.iliver.2024.100093
Cite this article:
Li F, Zhang Y, Liu C, et al. Clinical outcomes of cessation of nucleoside/nucleotide analogues in Chinese patients with HBeAg-negative chronic hepatitis B. iLIVER, 2024, 3(2): 100093. https://doi.org/10.1016/j.iliver.2024.100093

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Received: 25 October 2023
Revised: 25 January 2024
Accepted: 09 February 2024
Published: 27 March 2024
© 2024 Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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