Quantitative hepatitis B core antibody level may help predict treatment respon in chronic hepatitis B patients
W e read with interest the recent article by Dandri emphasising the u of novel quanti-tative biomarkers as tools for predicting treatment respon and dia progression in chronic hepatitis B infection(CHB).1The authors carried out a comprehensive review of the clinical implications of quantitative measurement of viral biomarkers both in blood and in liver,such as:rum HBsAg, rum HBeAg and intrahepatic cccDNA, bad on current knowledge.1In addition to the,we would like to propo a new potential prognostic biomarker in CHB:the quantitative hepatitis B core antibody (anti-HBc)level which may help predict treatment respon in CHB patients.
Anti-HBc is one of most classical ro-logical markers for HBV infection.2 However,the clinical significance of quanti-tative anti-HBc level is still largely unknown.By using a newly developed double-sandwich anti-HBc immunoassay validated by the WHO anti-HBc stan-dards,34we investigated its value in CHB patients.
新车保养常识>haikuIn a cross-ctional cohort,we analyd the anti-HBc levels of488CHB patients and350healthy individuals with past HBV infection.The geometric mean level of anti-HBc in CHB patients was>1000-fo
ld higher than that in individuals with past HBV infection(p<0.001,figure1A).Among CHB patients,the anti-HBc levels in tho who had elevated AL T levels(n=180)was significantly higher than tho who had normal AL T levels(n=308)(p<0.001,figure1A).Becau elevated AL T levels in CHB is assumed to be due to a T-cell-
mediated hepatocytolysis,5the parallel increasing anti-HBc levels may re flect the host-adaptive anti-HBV immune activity.Moreover,the quantitative anti-HBc,thus,might also predict the respon of patients receiving anti-HBV therapies.
T o test this hypothesis,we further retro-spectively investigated the ufulness of the baline anti-HBc levels in predicting post-treatment respon in two cohorts (A and B).Cohort A consisted of 49HBeAg-positive patients treated with adefovir dipi-voxil at 10mg/day for 96weeks and fol-lowed by a 12-week obrvation between years 2004–2007.Cohort B included 48HBeAg-positive patients receiving peginter-feron α-2a (180μg/week)for 24weeks,and followed by a 24-week obrvation in years 2005–2009(Cohort B).As shown in table 1,patients with and without HBeAg rocon-version (SR)at the end of follow-up in the two cohorts had comparable (p>0.05)ba-line values for age,gender,the levels of AL T (or strati fication by 5×ULN),HBV DNA,
HBsAg and anti-HBc-IgM.However,the SR (+)patients had a signi ficantly higher ba-line anti-HBc levels than SR(–)patients,either in cohort A (p=0.005)or B (p=0.011).The predictive value (indicated by area under the curve for SR of the ba-line anti-HBc level was 0.810(95%CI 0.675to 0.948,p=0.004)and 0.710(95%CI 0.564to 0.855,p=0.013)in cohorts A and B,respectively.Figure 1B showed the SR rate among patient groups classi fied by baline anti-HBc level using the optimal cut-off indicated by the in flection point of the receiver operating characteristic in both cohorts.Patients with high baline anti-HBc levels (≥29000IU/ml for cohort A or ≥9000IU/ml for cohort B)had a higher SR rate than tho with lower baline anti-HBc levels (RR=7.22,95%CI 1.69to 30.9,p=0.006in Cohort A;RR=2.10,95%CI 1.06to 4.17,p=0.021in Cohort B).The results suggested that the pre-treatment anti-HBc level may be an add-itional predictor for post-treatment SR both
Table 1Analys of baline characteristics predicting HBeAg roconversion (SR)in patients receiving adefovir dipivoxil (cohort A)and peginterferon (cohort B)treatments
Characteristics
Cohort A Cohort B SR(+)SR(−)p Value SR(+)SR(−)p Value No.940–2325–Age,yrs
35±436±60.8734±1136±100.54Gender,males/females 7/237/30.4517/618/70.88Genotype,B/C
2/79/310.9915/814/110.52ALT ,>5×/≤5×ULN 3/69/310.778/158/170.84ALT ,U/L
170±88137±790.28198±129213±1490.71HBV DNA,log 10copies/ml 7.03±1.407.65±1.130.167.64±0.927.04±1.610.12HBsAg,log 10IU/ml
4.32±0.16 4.39±0.650.78 4.01±0.42 3.92±1.070.70Anti-HBc-IgM,S/CO value 3.13±1.39 2.51±2.490.47 3.38±2.85 2.72±3.430.47Anti-HBc,log 10IU/ml
4.58±0.28
4.15±0.42
0.005
4.32±0.66
the crowded room
3.81±0.68
0.011
whicheverData of Age,ALT activity,HBV DNA,HBsAg titier,IgM anti-HBc and anti-HBc level are expresd at Mean±SD;SR,HBeAg
roconversion.
Figure 1The quantitative anti-HBc levels in patients experiencing HBV infection.(A)Distribution of the
rum anti-HBc levels during different phas of HBV infection.(B)The probability of roconversion bad on the baline anti-HBc level grouping (high or low)according to the ROC-determined cut-off in patients receiving adefovir dipivoxil (Cohort A,29000IU/ml)and peginterferon (Cohort B,9000IU/ml).PBI,past HBV infection;ULN,the upper normal limit.
in interferon or nucleos(t)ide analogue therapy.
In summary,baline anti-HBc levels may rve as a uful marker indicating an ongoing host-immune activity against HBV ,and the new findings may have clinical implications warranting further investigation.
Quan Yuan,1Liu-Wei Song,1Chun-Jen Liu,2Zhuo Li,3Ping-Guo Liu,4Cheng-Hao Huang,1Yan Yan,3Sheng-Xiang Ge,1Ying-Bin Wang,1
Cheng-Yuan Peng,5Jun Zhang,1Jia-Horng Kao,2Ding-Shinn Chen,2Pei-Jer Chen,2Ning-Shao Xia 11
National Institute of Diagnostics and Vaccine
Development in Infectious Dias,School of Public Health,Xiamen University,Xiamen,China;2Grad
uate Institute of Clinical Medicine and Department of Internal Medicine,National Taiwan University College of Medicine,Taipei,Taiwan;3Youan Hospital,Capital Medical University,Beijing,China;4Zhongshan Hospital and College of Medicine,Xiamen University,Xiamen,China;5China Medical University Hospital,China Medical University,Taichung,Taiwan
8 1 2
Correspondence to Professor Jun Zhang,National Institute of Diagnostics and Vaccine Development in Infectious Dias,School of Life Science,Xiamen University,Siming South Road No.422,Xiamen 361005.China;**************
Contributors JZ,NSX and PJC are co-corresponders for this paper.Study concept and design:QY ,JZ,P-JC and N-SX.Acquisition of data:QY ,L-WS,C-JL,C-HH,S-XG and Y-BW.Analysis and interpretation of data:QY ,L-WS,P-JC.Drafting of the manuscript:QY and P-JC.Critical revision of the manuscript for important intellectual content:P-JC,JZ,J-HK,D-SC and N-SX.Statistical analysis:QY and L-WS.Technical,or material support:C-JC,ZL,P-GL,YY and C-YP .Obtained funding:S-XG,JZ and N-SX.Study supervision:JZ and N-SX.Approval of the final version of the manuscript:P-JC,JZ and N-SX.
Funding Supported by grants from the National Scienti fic and Technological Major Project
smell(2012ZX10002-005);and acknowledgement of Taiwan Liver Consortium for patients recruitment.
Competing interests P-J Chen is a consultant for Novartis and Roche.D-S Chen is a consultant for Novartis and GlaxoSmithKline.J-H Kao is a consultant for Bristol-Myers Squibb,GlaxoSmithKline,Novartis,Omrix,and Roche;and is a member of the Speaker ’s Bureau for Roche,Bristol-Myers Squibb,GlaxoSmithKline,and Novartis.Patient connt Obtained.
Ethics approval This study was approved by the Ethics Committees of Zhongshan Hospital of Xiamen University.
Provenance and peer review Not commissioned;externally peer reviewed.
Accepted 15May 2012
Published Online First 26June 2012
Gut 2013;62:182–184.doi:10.1136/gutjnl-2012-302656mouth
▸/10.1136/gutjnl-2012-302056fromsport
REFERENCES
1.Dandri M,Locarnini S.New insight in the
pathobiology of hepatitis B virus infection.Gut
2012;61(Suppl1):i6–17.
2.Liaw YF,Chu CM.Hepatitis B virus infection.Lancet
2009;373:582–92.
3.Li A,Yuan Q,Huang Z,et al.Novel double-antigen
sandwich immunoassay for human hepatitis B core
antibody.Clin Vaccine Immunol2010;17:464–9.
英文杂志4.NIBSC.WHO International Standard:First International
Standard for anti-Hepatitis B core antigen.2008.
www.nibsc.ac.uk/documents/fu/95-522.pdf
5.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 Med2000;191:1269–80.
doi: 10.1136/gutjnl-2012-302656
2013 62: 182-184 originally published online June 14, 2012
dulaGut
Quan Yuan, Liu-Wei Song, Chun-Jen Liu, et al.
chronic hepatitis B patients
may help predict treatment respon in Quantitative hepatitis B core antibody level
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