Hepatitis B virus pre-genomic RNA and hepatitis B core-related antigen reductions at week 4 predict favourable hepatitis B surface antigen response upon long-term nucleos(t)ide analogue in chronic hepatitis B.
Chronic hepatitis B
Hepatitis B core antigen
Hepatitis B e antigen
Treatment outcome
Viremia
Journal
Clinical and molecular hepatology
ISSN: 2287-285X
Titre abrégé: Clin Mol Hepatol
Pays: Korea (South)
ID NLM: 101586730
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
14
06
2022
accepted:
12
08
2022
pubmed:
22
8
2022
medline:
18
1
2023
entrez:
21
8
2022
Statut:
ppublish
Résumé
We investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg). Serum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36, and 48 of treatment. Patients were followed up thereafter and serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU. Twenty-eight hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients (median, 38.2 years old; 71.9% male) were recruited with median follow-up duration of 17.1 years (interquartile range, 12.8-18.2). For the entire cohort, 22/64 (34.4%) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR (5.49 vs. 4.32 log copies/mL, respectively; P=0.016). The area under the receiver-operating-characteristic curve (AUROC) for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% confidence interval [CI], 0.661-0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs. reduction of 2.98 log U/mL; P=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI, 0.596-0.982). Early on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.
Sections du résumé
BACKGROUND/AIMS
We investigated the dynamics of serum HBV pre-genomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) in patients receiving nucleos(t)ide analogues (NAs) and their predictability for favourable suppression of serum hepatitis B surface antigen (HBsAg).
METHODS
Serum viral biomarkers were measured at baseline, weeks 4, 12, 24, 36, and 48 of treatment. Patients were followed up thereafter and serum HBsAg level was measured at end of follow-up (EOFU). Favourable HBsAg response (FHR) was defined as ≤100 IU/mL or HBsAg seroclearance upon EOFU.
RESULTS
Twenty-eight hepatitis B e antigen (HBeAg)-positive and 36 HBeAg-negative patients (median, 38.2 years old; 71.9% male) were recruited with median follow-up duration of 17.1 years (interquartile range, 12.8-18.2). For the entire cohort, 22/64 (34.4%) achieved FHR. For HBeAg-positive patients, serum HBV pgRNA decline at week 4 was significantly greater for patients with FHR compared to non-FHR (5.49 vs. 4.32 log copies/mL, respectively; P=0.016). The area under the receiver-operating-characteristic curve (AUROC) for week 4 HBV pgRNA reduction to predict FHR in HBeAg-positive patients was 0.825 (95% confidence interval [CI], 0.661-0.989). For HBeAg-negative patients, instead of increase in serum HBcrAg in non-FHR patients, FHR patients had median reduction in HBcrAg at week 4 (increment of 1.75 vs. reduction of 2.98 log U/mL; P=0.023). The AUROC for week 4 change of HBcrAg to predict FHR in HBeAg-negative patients was 0.789 (95% CI, 0.596-0.982).
CONCLUSION
Early on-treatment changes of serum HBV pgRNA and HBcrAg at 4 weeks predict HBsAg seroclearance or ≤100 IU/mL in NA-treated CHB patients upon long-term FU.
Identifiants
pubmed: 35989092
pii: cmh.2022.0172
doi: 10.3350/cmh.2022.0172
pmc: PMC9845664
doi:
Substances chimiques
Hepatitis B Surface Antigens
0
Hepatitis B Core Antigens
0
Hepatitis B e Antigens
0
RNA
63231-63-0
Antiviral Agents
0
Biomarkers
0
DNA, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
146-162Subventions
Organisme : Research Grants Council, The Government of the Hong Kong Special Administrative Region
ID : 17108921
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Références
Liver Int. 2017 Jul;37(7):995-1001
pubmed: 27992681
JHEP Rep. 2020 Mar 29;2(3):100112
pubmed: 32462119
JHEP Rep. 2021 Sep 08;3(6):100361
pubmed: 34661089
J Hepatol. 2013 May;58(5):853-60
pubmed: 23246508
Clin Transl Gastroenterol. 2017 Oct 26;8(10):e125
pubmed: 29072673
Am J Gastroenterol. 2011 Oct;106(10):1766-73
pubmed: 21826112
Hepatology. 2012 Jan;55(1):68-76
pubmed: 21858846
N Engl J Med. 2007 Dec 20;357(25):2576-88
pubmed: 18094378
Hepatology. 2019 Nov 12;:
pubmed: 31713892
J Clin Virol. 2022 Jun;150-151:105150
pubmed: 35427860
J Viral Hepat. 2018 Sep;25(9):1038-1047
pubmed: 29633430
Gastroenterology. 2011 Aug;141(2):517-25, 525.e1-2
pubmed: 21672542
Clin Microbiol Infect. 2014 Nov;20(11):1173-80
pubmed: 24975365
J Clin Microbiol. 2007 Dec;45(12):3942-7
pubmed: 17942661
N Engl J Med. 2006 Mar 9;354(10):1001-10
pubmed: 16525137
Gastroenterology. 2016 Nov;151(5):986-998.e4
pubmed: 27453547
Hepatology. 1999 Mar;29(3):971-5
pubmed: 10051505
Gut. 2021 Apr;70(4):775-783
pubmed: 32759300
J Hepatol. 2021 Aug;75(2):474-480
pubmed: 33957187
BMJ Open. 2013 Aug 14;3(8):
pubmed: 23945731
Clin Infect Dis. 2022 May 20;:
pubmed: 35594553
J Clin Microbiol. 2002 Feb;40(2):439-45
pubmed: 11825954
Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403
pubmed: 29599078
J Hepatol. 2017 Feb;66(2):460-462
pubmed: 27826059
Nat Med. 2021 Oct;27(10):1725-1734
pubmed: 34642494
Antivir Ther. 2006;11(7):909-16
pubmed: 17302253
Dig Dis Sci. 2015 May;60(5):1457-64
pubmed: 25532501
Methods Mol Biol. 2017;1540:97-118
pubmed: 27975311
Aliment Pharmacol Ther. 2018 Jan;47(1):43-54
pubmed: 29035003
Hepatology. 2021 Oct;74(4):1795-1808
pubmed: 34037271
J Clin Virol. 2018 Feb - Mar;99-100:71-78
pubmed: 29353073
Gut. 2010 Oct;59(10):1389-93
pubmed: 20675695
Hepatology. 2020 Jul;72(1):42-57
pubmed: 31701544
J Hepatol. 2017 Feb;66(2):275-281
pubmed: 27639844
J Viral Hepat. 2014 Nov;21(11):802-8
pubmed: 25274427
Am J Gastroenterol. 2016 Dec;111(12):1788-1795
pubmed: 27644733
J Hepatol. 2017 Sep 21;:
pubmed: 28870671
Hepatology. 2015 Jan;61(1):66-76
pubmed: 25132147
J Hepatol. 2016 Oct;65(4):700-710
pubmed: 27245431
BMC Gastroenterol. 2021 Mar 17;21(1):123
pubmed: 33731023
Clin Gastroenterol Hepatol. 2013 Aug;11(8):1004-10.e1
pubmed: 23376799
J Infect Dis. 2016 Jan 15;213(2):224-32
pubmed: 26216905
Hepatology. 2021 Jun;73(6):2167-2179
pubmed: 33159329
N Engl J Med. 2006 Mar 9;354(10):1011-20
pubmed: 16525138
Hepatology. 2018 Apr;67(4):1560-1599
pubmed: 29405329
Clin Microbiol Infect. 2015 Jun;21(6):606.e1-10
pubmed: 25700889
Aliment Pharmacol Ther. 2017 Feb;45(4):501-509
pubmed: 27976416
J Infect Dis. 2011 Aug 1;204(3):408-14
pubmed: 21742839
J Hepatol. 2017 Aug;67(2):370-398
pubmed: 28427875
Hepatology. 2019 Apr;69(4):1816-1827
pubmed: 30362148
BMC Gastroenterol. 2019 Apr 16;19(1):53
pubmed: 30991954
Sci Transl Med. 2017 Sep 27;9(409):
pubmed: 28954926
J Viral Hepat. 2020 Apr;27(4):397-406
pubmed: 31755196