Serum Hepatitis B Surface Antigen and Hepatitis B e Antigen Titers: Disease Phase Influences Correlation with Viral Load and Intrahepatic Hepatitis B Virus Markers

被引:373
作者
Thompson, Alexander J. V. [1 ,2 ]
Nguyen, Tin [1 ,2 ]
Iser, David [1 ,2 ,3 ]
Ayres, Anna [1 ]
Jackson, Kathy [1 ]
Littlejohn, Margaret [1 ]
Slavin, John [2 ]
Bowden, Scott [1 ]
Gane, Edward J. [4 ]
Abbott, William [4 ]
Lau, George K. K. [5 ]
Lewin, Sharon R. [3 ,6 ,7 ]
Visvanathan, Kumar [6 ,8 ]
Desmond, Paul V. [2 ]
Locarnini, Stephen A. [1 ]
机构
[1] VIDRL, Dept Res & Mol Dev, Melbourne, Vic 3051, Australia
[2] St Vincents Hosp, Dept Pathol, Melbourne, Vic, Australia
[3] Monash Univ, Alfred Hosp, Infect Dis Unit, Melbourne, Vic 3181, Australia
[4] Auckland City Hosp, New Zealand Liver Unit, Auckland, New Zealand
[5] Univ Hong Kong, Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China
[6] Monash Univ, Clayton, Vic, Australia
[7] Burnet Inst, Melbourne, Vic, Australia
[8] Monash Med Ctr, Dept Infect Dis, Clayton, Vic 3168, Australia
基金
英国医学研究理事会;
关键词
HBV DNA LEVELS; PEGINTERFERON ALPHA-2A; CORE PROMOTER; HBSAG LEVELS; HBEAG; INFECTION; REPLICATION; THERAPY; CCCDNA; INTEGRATION;
D O I
10.1002/hep.23571
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo. In all, 149 treatment-naive CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (r = 0.69, 0.71, 0.76, P < 0.01). HBeAg correlated with serum HBV DNA (r = 0.60, P < 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. Conclusion: The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker. (HEPATOLOGY 2010;51:1933-1944)
引用
收藏
页码:1933 / 1944
页数:12
相关论文
共 36 条
[1]  
Ayres A, 2004, METH MOLEC MED, V95, P125
[2]   An algorithm for the grading of activity in chronic hepatitis C [J].
Bedossa, P ;
Poynard, T .
HEPATOLOGY, 1996, 24 (02) :289-293
[3]   Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid integrity through activation of NF-κB [J].
Biermer, M ;
Puro, R ;
Schneider, RJ .
JOURNAL OF VIROLOGY, 2003, 77 (07) :4033-4042
[4]   Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration [J].
Bill, CA ;
Summers, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (30) :11135-11140
[5]  
Bowden S, 2004, METH MOLEC MED, V95, P41
[6]   Hepatitis B Virus Surface Antigen Levels: A Guide to Sustained Response to peginterferon alfa-2a in HBeAg-Negative Chronic Hepatitis B [J].
Brunetto, Maurizia Rossana ;
Moriconi, Francesco ;
Bonino, Ferruccio ;
Lau, George K. K. ;
Farci, Patrizia ;
Yurdaydin, Cihan ;
Piratvisuth, Teerha ;
Luo, Kanxian ;
Wang, Yuming ;
Hadziyannis, Stephanos ;
Wolf, Eva ;
McCloud, Philip ;
Batrla, Richard ;
Marcellin, Patrick .
HEPATOLOGY, 2009, 49 (04) :1141-1150
[7]  
CARMAN WF, 1989, LANCET, V2, P588
[8]   Correlation of quantitative assay of hepatitis B surface antigen and HBV DNA levels in asymptomatic hepatitis B virus carriers [J].
Chen, CH ;
Lee, CM ;
Wang, JH ;
Tung, HD ;
Hung, CH ;
Lu, SN .
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY, 2004, 16 (11) :1213-1218
[9]   The degrees of hepatocyte nuclear but not cytoplasmic expression of hepatitis B core antigen reflect the level of viral replication in chronic hepatitis B virus infection [J].
Chu, CM ;
Yeh, CT ;
Chien, RN ;
Sheen, IS ;
Liaw, YF .
JOURNAL OF CLINICAL MICROBIOLOGY, 1997, 35 (01) :102-105
[10]  
CHU CM, 1997, J GASTROEN HEPATOL, V12, P218