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Erschienen in: Digestive Diseases and Sciences 7/2022

09.07.2021 | Original Article

Predictors of Virological Suppression After Clinical Relapse in Patients Who Discontinued Entecavir or Tenofovir

verfasst von: Hsin-Wei Fang, Yi-Hao Yen, Chao-Hung Hung, Jing-Houng Wang, Tsung-Hui Hu, Sheng-Nan Lu, Chien-Hung Chen

Erschienen in: Digestive Diseases and Sciences | Ausgabe 7/2022

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Abstract

Background

The predictors of persistent virological suppression after clinical relapse remain unclear.

Aims

To investigate the predictors of retreatment or persistent virological suppression after clinical relapse in chronic hepatitis B (CHB) patients who discontinued entecavir or tenofovir disoproxil fumarate (TDF).

Methods

A total of 243 hepatitis B e antigen-negative CHB patients without cirrhosis who experienced clinical relapse after entecavir or TDF cessation were enrolled.

Results

Of the 243 CHB patients, 192 received retreatment and 51 did not receive retreatment after clinical relapse. Of the 51 patients without retreatment, 23 achieved persistent virological suppression (persistent HBV DNA < 2000 IU/mL at least 2 years) and 10 experienced hepatitis B surface antigen (HBsAg) loss. The Cox regression analysis showed that short consolidation duration, short duration of the first clinical relapse from the end of treatment (EOT), and high bilirubin and HBV DNA levels at the first clinical relapse were independent predictors of retreatment. Long duration of the first clinical relapse from the EOT and low HBsAg levels at the first clinical relapse were independent factors of patients with persistent virological suppression. The rates of persistent virological suppression at the first clinical relapse among patients with HBsAg < 100 and ≥ 100 IU/mL were 44.4% (12/27) and 5.1% (11/216) (P < 0.001), respectively. Baseline HBsAg levels and no retreatment requirement were independent factors associated with HBsAg loss.

Conclusions

The HBsAg of 100 IU/mL at the first clinical relapse could predict persistent virological suppression after clinical relapse in patients who discontinued entecavir or TDF therapy.
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Literatur
1.
Zurück zum Zitat Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008;48:335–352.CrossRef Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008;48:335–352.CrossRef
2.
Zurück zum Zitat Liaw YF, Chu CM. Hepatitis B virus infection. Lancet (London, England) 2009;373:582–592.CrossRef Liaw YF, Chu CM. Hepatitis B virus infection. Lancet (London, England) 2009;373:582–592.CrossRef
3.
Zurück zum Zitat 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.CrossRef 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.CrossRef
4.
Zurück zum Zitat European Association for the Study of the Liver. Electronic address, European Association for the Study of the L. EASL. Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;2017:370–398. European Association for the Study of the Liver. Electronic address, European Association for the Study of the L. EASL. Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2017;2017:370–398.
5.
Zurück zum Zitat Terrault NA, Lok ASF, McMahon BJ et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology (Baltimore, Md.) 2018;67:1560–1599.CrossRef Terrault NA, Lok ASF, McMahon BJ et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology (Baltimore, Md.) 2018;67:1560–1599.CrossRef
6.
Zurück zum Zitat Jeng WJ, Sheen IS, Chen YC et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology 2013;58:1888–1896.CrossRef Jeng WJ, Sheen IS, Chen YC et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology 2013;58:1888–1896.CrossRef
7.
Zurück zum Zitat 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.CrossRef 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.CrossRef
8.
Zurück zum Zitat Chen CH, Hung CH, Hu TH et al. Association between level of hepatitis B surface antigen and relapse after entecavir therapy for chronic HBV infection. Clin Gastroenterol Hepatol 2015;13:1984–1992.CrossRef Chen CH, Hung CH, Hu TH et al. Association between level of hepatitis B surface antigen and relapse after entecavir therapy for chronic HBV infection. Clin Gastroenterol Hepatol 2015;13:1984–1992.CrossRef
9.
Zurück zum Zitat Chen CH, Hsu YC, Lu SN et al. The incidence and predictors of HBV relapse after cessation of tenofovir therapy in chronic hepatitis B patients. J Viral Hepat 2018;25:590–597.CrossRef Chen CH, Hsu YC, Lu SN et al. The incidence and predictors of HBV relapse after cessation of tenofovir therapy in chronic hepatitis B patients. J Viral Hepat 2018;25:590–597.CrossRef
10.
Zurück zum Zitat Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology 2009;49:S185–S195.CrossRef Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology 2009;49:S185–S195.CrossRef
11.
Zurück zum Zitat 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.CrossRef 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.CrossRef
12.
Zurück zum Zitat Berg T, Simon K-G, Mauss S et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients—FINITE study. J Hepatol 2017;67:918–924.CrossRef Berg T, Simon K-G, Mauss S et al. Long-term response after stopping tenofovir disoproxil fumarate in non-cirrhotic HBeAg-negative patients—FINITE study. J Hepatol 2017;67:918–924.CrossRef
13.
Zurück zum Zitat 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;68:425–434.CrossRef 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;68:425–434.CrossRef
14.
Zurück zum Zitat Chen CH, Hung CH, Wang JH, Lu SN, Hu TH, Lee CM. Long-term incidence and predictors of hepatitis B surface antigen loss after discontinuing nucleoside analogues in noncirrhotic chronic hepatitis B patients. Clin Microbiol Infect 2018;24:997–1003.CrossRef Chen CH, Hung CH, Wang JH, Lu SN, Hu TH, Lee CM. Long-term incidence and predictors of hepatitis B surface antigen loss after discontinuing nucleoside analogues in noncirrhotic chronic hepatitis B patients. Clin Microbiol Infect 2018;24:997–1003.CrossRef
15.
Zurück zum Zitat Liaw YF, Jeng WJ, Chang ML. HBsAg kinetics in retreatment decision for off-therapy hepatitis B flare in HBeAg-negative patients. Gastroenterology 2018;154:2280–2281.CrossRef Liaw YF, Jeng WJ, Chang ML. HBsAg kinetics in retreatment decision for off-therapy hepatitis B flare in HBeAg-negative patients. Gastroenterology 2018;154:2280–2281.CrossRef
16.
Zurück zum Zitat Liaw YF, Kao JH, Piratvisuth T et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int 2012;6:531–561.CrossRef Liaw YF, Kao JH, Piratvisuth T et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int 2012;6:531–561.CrossRef
17.
Zurück zum Zitat European Association for Study of Liver. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015;63:237–264.CrossRef European Association for Study of Liver. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015;63:237–264.CrossRef
18.
Zurück zum Zitat Lee CM, Chen CH, Lu SN et al. Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan. Scand J Gastroenterol 2003;38:95–101.CrossRef Lee CM, Chen CH, Lu SN et al. Prevalence and clinical implications of hepatitis B virus genotypes in southern Taiwan. Scand J Gastroenterol 2003;38:95–101.CrossRef
19.
Zurück zum Zitat Heagerty PJ, Lumley T, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 2000;56:337–344.CrossRef Heagerty PJ, Lumley T, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 2000;56:337–344.CrossRef
20.
Zurück zum Zitat Ma TL, Hu TH, Hung CH, Wang JH, Lu SN, Chen CH. Incidence and predictors of retreatment in chronic hepatitis B patients after discontinuation of entecavir or tenofovir treatment. PLoS ONE 2019;14:e0222221.CrossRef Ma TL, Hu TH, Hung CH, Wang JH, Lu SN, Chen CH. Incidence and predictors of retreatment in chronic hepatitis B patients after discontinuation of entecavir or tenofovir treatment. PLoS ONE 2019;14:e0222221.CrossRef
21.
Zurück zum Zitat Chiu SM, Kuo YH, Wang JH et al. Associations of HBV genotype B vs C infection with relapse after cessation of entecavir or tenofovir therapy. Clin Gastro Hepatol 2020;18:2989–2997.CrossRef Chiu SM, Kuo YH, Wang JH et al. Associations of HBV genotype B vs C infection with relapse after cessation of entecavir or tenofovir therapy. Clin Gastro Hepatol 2020;18:2989–2997.CrossRef
22.
Zurück zum Zitat Papatheodoridis GV, Rigopoulou EI, Papatheodoridi M et al. DARING-B: discontinuation of effective entecavir or tenofovir disoproxil fumarate long-term therapy before HBsAg loss in non-cirrhotic HBeAg-negative chronic hepatitis B. Antivir Ther 2018;23:677–685.CrossRef Papatheodoridis GV, Rigopoulou EI, Papatheodoridi M et al. DARING-B: discontinuation of effective entecavir or tenofovir disoproxil fumarate long-term therapy before HBsAg loss in non-cirrhotic HBeAg-negative chronic hepatitis B. Antivir Ther 2018;23:677–685.CrossRef
23.
Zurück zum Zitat Lampertico P. Oral antiviral therapy for HBeAg negative chronic hepatitis B: better stop or continue? Gut 2015;64:526–552.CrossRef Lampertico P. Oral antiviral therapy for HBeAg negative chronic hepatitis B: better stop or continue? Gut 2015;64:526–552.CrossRef
24.
Zurück zum Zitat Kuo MT, Hu TH, Hung CH et al. Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir. Aliment Pharmacol Ther 2019;49:218–228.CrossRef Kuo MT, Hu TH, Hung CH et al. Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir. Aliment Pharmacol Ther 2019;49:218–228.CrossRef
Metadaten
Titel
Predictors of Virological Suppression After Clinical Relapse in Patients Who Discontinued Entecavir or Tenofovir
verfasst von
Hsin-Wei Fang
Yi-Hao Yen
Chao-Hung Hung
Jing-Houng Wang
Tsung-Hui Hu
Sheng-Nan Lu
Chien-Hung Chen
Publikationsdatum
09.07.2021
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 7/2022
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-021-07128-6

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