When can we stop nucleoside analogues in patients with chronic hepatitis B?

Liver International

Volumn 37, Issue , 2017, Pages 52-58

  Chong, Chern Hao ^a   Lim, Seng Gee ^a,b  

^a NATIONAL UNIVERSITY HEALTH SYSTEM   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

antiviral therapy; cessation; hepatitis B flares; nucleos(t)ide analogues; quantitative HBsAg; relapse; seroreversion; treatment withdrawal

Indexed keywords

ANTIVIRUS AGENT; HEPATITIS B SURFACE ANTIGEN; HEPATITIS B(E) ANTIGEN; NUCLEOSIDE ANALOG;

CHRONIC HEPATITIS B; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; HUMAN; LIVER CIRRHOSIS; NONHUMAN; PATIENT IDENTIFICATION; PATIENT SELECTION; PRACTICE GUIDELINE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RELAPSE; REVIEW; SEROCONVERSION; SUSTAINED VIROLOGIC RESPONSE; SYSTEMATIC REVIEW (TOPIC); TREATMENT RESPONSE; BLOOD; HEPATITIS B VIRUS; RECURRENT DISEASE; TREATMENT OUTCOME;

ANTIVIRAL AGENTS; HEPATITIS B E ANTIGENS; HEPATITIS B SURFACE ANTIGENS; HEPATITIS B VIRUS; HEPATITIS B, CHRONIC; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECURRENCE; SUSTAINED VIROLOGIC RESPONSE; TREATMENT OUTCOME;

EID: 85007593110     PISSN: 14783223     EISSN: 14783231     Source Type: Journal    
DOI: 10.1111/liv.13314     Document Type: Review

References (52)

1. World Health Organisation. WHO Factsheet: Hepatitis B: World Health Organisation; 2016. Report No.: 204.
2. McMahon BJ. Natural history of chronic hepatitis B. Clin Liver Dis. 2010;14:381–396.
3. Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261–283.
4. European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–185.
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;10:1–98.
6. Jie Y, Li X, Lin G, et al. Real-life practice of antiviral therapy and disease patterns of patients with chronic hepatitis B: a single-center retrospective observation study. Hepatol Int. 2014;8:501–507.
7. Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology. 2016;63:284–306.
8. Zeisel MB, Lucifora J, Mason WS, et al. Towards an HBV cure: state-of-the-art and unresolved questions–report of the ANRS workshop on HBV cure. Gut. 2015;64:1314–1326.
9. 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;63:1325–1332.
10. Liaw Y-F, Leung N, Kao J-H, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hep Intl. 2008;2:263–283.
11. Dienstag JL, Cianciara J, Karayalcin S, et al. Durability of serologic response after lamivudine treatment of chronic hepatitis B. Hepatology. 2003;37:748–755.
12. Song BC, Suh DJ, Lee HC, Chung YH, Lee YS. Hepatitis B e antigen seroconversion after lamivudine therapy is not durable in patients with chronic hepatitis B in Korea. Hepatology. 2000;32(4 Pt 1):803–806.
13. Lee HW, Lee HJ, Hwang JS, et al. Lamivudine maintenance beyond one year after HBeAg seroconversion is a major factor for sustained virologic response in HBeAg-positive chronic hepatitis B. Hepatology. 2010;51:415–421.
14. Papatheodoridis G, Vlachogiannakos I, Cholongitas E, et al. Discontinuation of oral antivirals in chronic hepatitis B: a systematic review. Hepatology. 2016;63:1481–1492.
15. Qiu YW, Huang LH, Yang WL, et al. Hepatitis B surface antigen quantification at hepatitis B e antigen seroconversion predicts virological relapse after the cessation of entecavir treatment in hepatitis B e antigen-positive patients. Int J Infect Dis. 2016;43:43–48.
16. Yao CC, Lee CM, Hung CH, et al. Combining age and HBsAg level predicts post-treatment durability of nucleos(t)ide analogue-induced HBeAg seroconversion. J Gastroenterol Hepatol. 2015;30:918–924.
17. Fung J, Lai CL, Tanaka Y, et al. The duration of lamivudine therapy for chronic hepatitis B: cessation vs. continuation of treatment after HBeAg seroconversion. Am J Gastroenterol. 2009;104:1940–1946; quiz 47.
18. 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;42:243–257.
19. Pan HY, Pan HY, Chen L, et al. Ten-year follow-up of hepatitis B relapse after cessation of lamivudine or telbivudine treatment in chronic hepatitis B patients. Clin Microbiol Infect. 2015;21:1123 e1–9.
20. Lim SG, Wai CT, Rajnakova A, Kajiji T, Guan R. Fatal hepatitis B reactivation following discontinuation of nucleoside analogues for chronic hepatitis B. Gut. 2002;51:597–599.
21. Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–1531.
22. Chen YC, Peng CY, Jeng WJ, Chien RN, Liaw YF. Clinical outcomes after interruption of entecavir therapy in HBeAg-negative chronic hepatitis B patients with compensated cirrhosis. Aliment Pharmacol Ther. 2015;42:1182–1191.
23. Chang ML, Jeng WJ, Liaw YF. Clinical events after cessation of lamivudine therapy in patients recovered from hepatitis B flare with hepatic decompensation. Clin Gastroenterol Hepatol. 2015;13:979–986.
24. Jeng WJ, Chen YC, Sheen IS, et al. Clinical relapse after cessation of tenofovir therapy in HBeAg-negative patients. Clin Gastroenterol Hepatol. 2016;14:1813–1820.
25. Hadziyannis SJ, Sevastianos V, Rapti I, Vassilopoulos D, Hadziyannis E. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology. 2012;143:629–636 e1.
26. Chan HL, Wong GL, Chim AM, Chan HY, Chu SH, Wong VW. Prediction of off-treatment response to lamivudine by serum hepatitis B surface antigen quantification in hepatitis B e antigen-negative patients. Antivir Ther. 2011;16:1249–1257.
27. Chen CH, Lu SN, Hung CH, et al. The role of hepatitis B surface antigen quantification in predicting HBsAg loss and HBV relapse after discontinuation of lamivudine treatment. J Hepatol. 2014;61:515–522.
28. Berg T, Simon K-G, Mauss S, et al. Stopping Tenofovir Disoproxil Fumarate (TDF) Treatment After Long Term Virologic Suppression in HBeAg-Negative CHB: Week 48 Interim Results From an Ongoing Randomized, Controlled Trial (“Finite CHB”). Vienna, Austria: European Association for Study of Liver; 2015.
29. Ge GH, Ye Y, Zhou XB, et al. Hepatitis B surface antigen levels of cessation of nucleos(t)ide analogs associated with virological relapse in hepatitis B surface antigen-negative chronic hepatitis B patients. World J Gastroenterol. 2015;21:8653–8659.
30. Liang Y, Jiang J, Su M, et al. Predictors of relapse in chronic hepatitis B after discontinuation of anti-viral therapy. Aliment Pharmacol Ther. 2011;34:344–352.
31. Seto WK, Hui AJ, Wong VW, et al. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut. 2015;64:667–672.
32. Wang CC, Tseng KC, Hsieh TY, Tseng TC, Lin HH, Kao JH. Assessing the durability of entecavir-treated hepatitis B using quantitative HBsAg. Am J Gastroenterol. 2016;111:1286–1294.
33. Manesis EK, Hadziyannis ES, Angelopoulou OP, Hadziyannis SJ. Prediction of treatment-related HBsAg loss in HBeAG-negative chronic hepatitis B: a clue from serum HBsAg levels. Antivir Ther. 2007;12:73–82.
34. Hara T, Suzuki F, Kawamura Y, et al. Long-term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide-naive chronic hepatitis B patients. J Viral Hepat. 2014;21:802–808.
35. Hosaka T, Suzuki F, Kobayashi M, et al. Clearance of hepatitis B surface antigen during long-term nucleot(s)ide analog treatment in chronic hepatitis B: results from a nine-year longitudinal study. J Gastroenterol. 2013;48:930–941.
36. Chi H, Hansen BE, Yim C, et al. Reduced risk of relapse after long-term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B. Aliment Pharmacol Ther. 2015;41:867–876.
37. Fong TL, Tien A, Jo KJ, et al. Durability of hepatitis B e antigen seroconversion in chronic hepatitis B patients treated with entecavir or tenofovir. Dig Dis Sci. 2015;60:3465–3472.
38. Jun BG, Lee SH, Kim HS, et al. Predictive Factors for Sustained Remission after Discontinuation of Antiviral Therapy in Patients with HBeAg-positive Chronic Hepatitis B. Korean J Gastroenterol. 2016;67:28–34.
39. Kuo LF, Lee CM, Hung CH, et al. High risk of hepatitis B virus reactivation in nucleos(t)ide analogue-induced hepatitis B e antigen seroconverters older than 40 years. Dig Dis Sci. 2014;59:2580–2587.
40. Kuo YH, Chen CH, Wang JH, et al. Extended lamivudine consolidation therapy in hepatitis B e antigen-positive chronic hepatitis B patients improves sustained hepatitis B e antigen seroconversion. Scand J Gastroenterol. 2010;45:75–81.
41. Lee CM, Ong GY, Lu SN, et al. Durability of lamivudine-induced HBeAg seroconversion for chronic hepatitis B patients with acute exacerbation. J Hepatol. 2002;37:669–674.
42. Pan X, Zhang K, Yang X, et al. Relapse rate and associated-factor of recurrence after stopping NUCs therapy with different prolonged consolidation therapy in HBeAg positive CHB patients. PLoS One. 2013;8:e68568.
43. Ryu SH, Chung YH, Choi MH, et al. Long-term additional lamivudine therapy enhances durability of lamivudine-induced HBeAg loss: a prospective study. J Hepatol. 2003;39:614–619.
44. Song MJ, Song DS, Kim HY, et al. Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B. World J Gastroenterol. 2012;18:6277–6283.
45. Tseng TC, Liu CJ, Su TH, et al. Young chronic hepatitis B patients with nucleos(t)ide analogue-induced hepatitis B e antigen seroconversion have a higher risk of HBV reactivation. J Infect Dis. 2012;206:1521–1531.
46. Van Nunen AB, Hansen BE, Suh DJ, et al. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and alanine aminotransferase. Gut. 2003;52:420–424.
47. Wang LC, Chen EQ, Cao J, et al. Combination of Lamivudine and adefovir therapy in HBeAg-positive chronic hepatitis B patients with poor response to adefovir monotherapy. J Viral Hepat. 2010;17:178–184.
48. He D, Guo S, Chen W, et al. Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative. BMC Infect Dis. 2013;13:458.
49. Kim HY, Choi JY, Park CH, et al. Outcome after discontinuing antiviral agents during pregnancy in women infected with hepatitis B virus. J Clin Virol. 2013;56:299–305.
50. Jiang JN, Huang ZL, He LX, et al. Residual amount of HBV DNA in serum is related to relapse in chronic hepatitis B patients after cessation of nucleos(t)ide analogs. J Clin Gastroenterol. 2015;49:323–328.
51. Lee IC, Sun CK, Su CW, et al. Durability of nucleos(t)ide analogues treatment in patients with chronic hepatitis B. Medicine (Baltimore). 2015;94:e1341.
52. Jung KS, Park JY, Chon YE, et al. Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients. J Gastroenterol. 2016;51:830–839.