Skip to main content
Top
Published in: Hepatology International 1/2013

Open Access 01-03-2013 | Original Article

Serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B

Authors: Wai-Kay Seto, Danny Ka-Ho Wong, James Fung, Ivan Fan-Ngai Hung, John Chi-Hang Yuen, Teresa Tong, Ching-Lung Lai, Man-Fung Yuen

Published in: Hepatology International | Issue 1/2013

Login to get access

Abstract

Background

We investigated the differences in HBsAg kinetics at different levels of viremia in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB).

Methods

We compared HBsAg levels among HBeAg-negative CHB patients with persistently undetectable HBV DNA (≤20 IU/mL; Group A, n = 100), HBV DNA 20–2,000 IU/mL (Group B, n = 100), and HBV DNA >2,000 IU/mL (Group C, n = 100). HBsAg and HBV DNA levels were measured at three consecutive time points during follow-up (median 21.4 months).

Results

Median HBsAg levels were significantly lower in Group A than in Groups B and C at all time points (p < 0.001). HBV DNA and HBsAg levels were weakly correlated (r = 0.180 and 0.151 for Groups B and C, respectively). Among patients with HBsAg <100 IU/mL, Group A patients had the greatest median serum HBsAg reduction (0.341 log IU/mL/year; Group B, 0.122 log IU/mL/year; Group C, 0.057 log IU/mL/year; p = 0.002). Among Group A patients with HBsAg <100 IU/mL, baseline HBsAg achieved an AUROC of 0.876 in predicting >1 log annual HBsAg reduction; 10–100 IU/mL HBsAg was the optimal level for prediction (sensitivity 90 %; specificity 74.6 %). Serum HBsAg/HBV DNA ratios were significantly higher in Group B than in Groups A and C (p < 0.05).

Conclusions

HBV DNA and HBsAg were weakly correlated. Only patients with undetectable HBV DNA showed decline in HBsAg levels during follow-up. The greatest reduction in HBsAg levels occurred in patients with baseline HBsAg <100 IU/mL.
Literature
1.
go back to reference Fung J, Seto WK, Lai CL, et al. Profiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: implications for antiviral therapy. J Hepatol 2011;54(2):195–200PubMedCrossRef Fung J, Seto WK, Lai CL, et al. Profiles of HBV DNA in a large population of Chinese patients with chronic hepatitis B: implications for antiviral therapy. J Hepatol 2011;54(2):195–200PubMedCrossRef
2.
go back to reference Chu CJ, Keeffe EB, Han SH, et al. Prevalence of HBV precore/core promoter variants in the United States. Hepatology 2003;38(3):619–628PubMedCrossRef Chu CJ, Keeffe EB, Han SH, et al. Prevalence of HBV precore/core promoter variants in the United States. Hepatology 2003;38(3):619–628PubMedCrossRef
3.
go back to reference Zarski JP, Marcellin P, Leroy V, et al. Characteristics of patients with chronic hepatitis B in France: predominant frequency of HBe antigen negative cases. J Hepatol 2006;45(3):355–360PubMedCrossRef Zarski JP, Marcellin P, Leroy V, et al. Characteristics of patients with chronic hepatitis B in France: predominant frequency of HBe antigen negative cases. J Hepatol 2006;45(3):355–360PubMedCrossRef
4.
go back to reference Di Bisceglie AM, Waggoner JG, Hoofnagle JH. Hepatitis B virus deoxyribonucleic acid in liver of chronic carriers. Correlation with serum markers and changes associated with loss of hepatitis B e antigen after antiviral therapy. Gastroenterology 1987;93(6):1236–1241PubMed Di Bisceglie AM, Waggoner JG, Hoofnagle JH. Hepatitis B virus deoxyribonucleic acid in liver of chronic carriers. Correlation with serum markers and changes associated with loss of hepatitis B e antigen after antiviral therapy. Gastroenterology 1987;93(6):1236–1241PubMed
5.
go back to reference Lai CL, Yuen MF. The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points. Ann Intern Med 2007;147(1):58–61PubMed Lai CL, Yuen MF. The natural history and treatment of chronic hepatitis B: a critical evaluation of standard treatment criteria and end points. Ann Intern Med 2007;147(1):58–61PubMed
6.
go back to reference Chen JD, Yang HI, Iloeje UH, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010;138(5):1747–1754PubMedCrossRef Chen JD, Yang HI, Iloeje UH, et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010;138(5):1747–1754PubMedCrossRef
7.
go back to reference Yuen MF, Yuan HJ, Wong DK, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 2005;54(11):1610–1614PubMedCrossRef Yuen MF, Yuan HJ, Wong DK, et al. Prognostic determinants for chronic hepatitis B in Asians: therapeutic implications. Gut 2005;54(11):1610–1614PubMedCrossRef
8.
go back to reference Brunetto MR, Oliveri F, Coco B, et al. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study. J Hepatol 2002;36(2):263–270PubMedCrossRef Brunetto MR, Oliveri F, Coco B, et al. Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study. J Hepatol 2002;36(2):263–270PubMedCrossRef
9.
go back to reference Feld JJ, Ayers M, El-Ashry D, et al. Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B. Hepatology 2007;46(4):1057–1070PubMedCrossRef Feld JJ, Ayers M, El-Ashry D, et al. Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B. Hepatology 2007;46(4):1057–1070PubMedCrossRef
10.
go back to reference Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130(3):678–686PubMedCrossRef Iloeje UH, Yang HI, Su J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130(3):678–686PubMedCrossRef
11.
go back to reference Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295(1):65–73PubMedCrossRef Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295(1):65–73PubMedCrossRef
12.
go back to reference Chen CF, Lee WC, Yang HI, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology 2011;141(4):1240–1248.e2 Chen CF, Lee WC, Yang HI, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology 2011;141(4):1240–1248.e2
13.
go back to reference Yuen MF, Tanaka Y, Shinkai N, et al. Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels. Gut 2008;57(1):98–102PubMedCrossRef Yuen MF, Tanaka Y, Shinkai N, et al. Risk for hepatocellular carcinoma with respect to hepatitis B virus genotypes B/C, specific mutations of enhancer II/core promoter/precore regions and HBV DNA levels. Gut 2008;57(1):98–102PubMedCrossRef
14.
go back to reference Fung J, Lai CL, Yuen MF. Hepatitis B virus DNA and hepatitis B surface antigen levels in chronic hepatitis B. Expert Rev Anti Infect Ther 2010;8(6):717–726PubMedCrossRef Fung J, Lai CL, Yuen MF. Hepatitis B virus DNA and hepatitis B surface antigen levels in chronic hepatitis B. Expert Rev Anti Infect Ther 2010;8(6):717–726PubMedCrossRef
15.
go back to reference Wursthorn K, Lutgehetmann M, Dandri M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology 2006;44(3):675–684PubMedCrossRef Wursthorn K, Lutgehetmann M, Dandri M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology 2006;44(3):675–684PubMedCrossRef
16.
go back to reference Volz T, Lutgehetmann M, Wachtler P, et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. Gastroenterology 2007;133(3):843–852PubMedCrossRef Volz T, Lutgehetmann M, Wachtler P, et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. Gastroenterology 2007;133(3):843–852PubMedCrossRef
17.
go back to reference Thompson AJ, Nguyen T, Iser D, et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology 2010;51(6):1933–1944PubMedCrossRef Thompson AJ, Nguyen T, Iser D, et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology 2010;51(6):1933–1944PubMedCrossRef
18.
go back to reference Chan HL, Wong VW, Wong GL, et al. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B. Hepatology 2010;52(4):1232–1241PubMedCrossRef Chan HL, Wong VW, Wong GL, et al. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B. Hepatology 2010;52(4):1232–1241PubMedCrossRef
19.
go back to reference Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. J Hepatol 2010;52(4):514–522PubMedCrossRef Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. J Hepatol 2010;52(4):514–522PubMedCrossRef
20.
go back to reference Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010;52(4):508–513PubMedCrossRef Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010;52(4):508–513PubMedCrossRef
21.
go back to reference Brunetto MR, Oliveri F, Colombatto P, et al. Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010;139(2):483–490PubMedCrossRef Brunetto MR, Oliveri F, Colombatto P, et al. Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010;139(2):483–490PubMedCrossRef
22.
go back to reference Liu J, Yang HI, Lee MH, et al. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology 2010;139(2):474–482PubMedCrossRef Liu J, Yang HI, Lee MH, et al. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology 2010;139(2):474–482PubMedCrossRef
23.
go back to reference Tseng TC, Liu CJ, Su TH, et al. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology 2011;141(2):517–525PubMedCrossRef Tseng TC, Liu CJ, Su TH, et al. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology 2011;141(2):517–525PubMedCrossRef
24.
go back to reference Chan HL, Wong GL, Tse CH, et al. Viral determinants of hepatitis B surface antigen seroclearance in hepatitis B e antigen-negative chronic hepatitis B patients. J Infect Dis 2011;204(3):408–414PubMedCrossRef Chan HL, Wong GL, Tse CH, et al. Viral determinants of hepatitis B surface antigen seroclearance in hepatitis B e antigen-negative chronic hepatitis B patients. J Infect Dis 2011;204(3):408–414PubMedCrossRef
25.
go back to reference Yuen MF, Wong DK, Fung J, et al. HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology 2008;135(4):1192–1199PubMedCrossRef Yuen MF, Wong DK, Fung J, et al. HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology 2008;135(4):1192–1199PubMedCrossRef
26.
go back to reference Kuhns M, McNamara A, Mason A, et al. Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen. Gastroenterology 1992;103(5):1649–1656PubMed Kuhns M, McNamara A, Mason A, et al. Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen. Gastroenterology 1992;103(5):1649–1656PubMed
27.
go back to reference Bill CA, Summers J. Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration. Proc Natl Acad Sci USA 2004;101(30):11135–11140PubMedCrossRef Bill CA, Summers J. Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration. Proc Natl Acad Sci USA 2004;101(30):11135–11140PubMedCrossRef
28.
go back to reference Wong DK, Yuen MF, Yuan H, et al. Quantitation of covalently closed circular hepatitis B virus DNA in chronic hepatitis B patients. Hepatology 2004;40(3):727–737PubMedCrossRef Wong DK, Yuen MF, Yuan H, et al. Quantitation of covalently closed circular hepatitis B virus DNA in chronic hepatitis B patients. Hepatology 2004;40(3):727–737PubMedCrossRef
29.
go back to reference Kimura T, Rokuhara A, Sakamoto Y, et al. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load. J Clin Microbiol 2002;40(2):439–445PubMedCrossRef Kimura T, Rokuhara A, Sakamoto Y, et al. Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load. J Clin Microbiol 2002;40(2):439–445PubMedCrossRef
30.
go back to reference Tanaka E, Matsumoto A, Suzuki F, et al. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance. Liver Int 2006;26(1):90–96PubMedCrossRef Tanaka E, Matsumoto A, Suzuki F, et al. Measurement of hepatitis B virus core-related antigen is valuable for identifying patients who are at low risk of lamivudine resistance. Liver Int 2006;26(1):90–96PubMedCrossRef
31.
go back to reference Fung J, Lai CL, Young J, et al. Quantitative hepatitis B surface antigen levels in patients with chronic hepatitis B after 2 years of entecavir treatment. Am J Gastroenterol 2011;106(10):1766–1773PubMedCrossRef Fung J, Lai CL, Young J, et al. Quantitative hepatitis B surface antigen levels in patients with chronic hepatitis B after 2 years of entecavir treatment. Am J Gastroenterol 2011;106(10):1766–1773PubMedCrossRef
32.
go back to reference Sugiyama M, Tanaka Y, Kato T, et al. Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology 2006;44(4):915–924PubMedCrossRef Sugiyama M, Tanaka Y, Kato T, et al. Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology 2006;44(4):915–924PubMedCrossRef
Metadata
Title
Serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B
Authors
Wai-Kay Seto
Danny Ka-Ho Wong
James Fung
Ivan Fan-Ngai Hung
John Chi-Hang Yuen
Teresa Tong
Ching-Lung Lai
Man-Fung Yuen
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 1/2013
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-012-9373-4

Other articles of this Issue 1/2013

Hepatology International 1/2013 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.