title: Repeated Measurements of Hepatitis B Surface Antigen Identify Carriers of Inactive HBV During Long-term Follow-up.
abstract: Measurements of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA might help to identify carriers of inactive HBV. We assessed the performance of repeated measurements of HBsAg over a median time period of 8 years.
  
  
  
  We performed a retrospective study of 292 HBe antigen-negative patients with chronic HBV infection, normal levels of alanine aminotransferase (ALT), levels of HBV DNA <20,000 IU/mL, and no cirrhosis who visited the outpatient clinics at 8 tertiary care centers in Europe, Asia, and Australia from 1990 through 2011. Patients were determined to be carriers of inactive HBV (level of HBV DNA <2000 IU/mL and serum levels of ALT that remained normal) or to have HBV activity (level of HBV DNA fluctuating >2000 IU/mL and/or abnormal levels of ALT) after each year of follow-up. Patients were followed for a median time of 8 years (range, 4-9 years). Dynamic regression analysis was used to study changes in level of HBsAg and HBV phase and to update the risk of HBV activity.
  
  
  
  One year after study enrollment, 189 patients (65%) had inactive HBV and 103 patients (35%) had HBV activity. Based on dynamic analysis, the probability that a patient would have HBV at any following year differed according to level of HBsAg; odds were 97% for patients with initial level of HBsAg <100 IU/mL, 85% for patients with initial levels 100-1000 IU/mL, and 76% for patients with initial levels >1000 IU/mL (P < .001). Having inactive virus for any 2 consecutive years predicted having inactive virus in any third year. However, 15% of patients with level of HBsAg >100 IU/mL had HBV activity in the third year. The combination of HBsAg level <100 IU/mL and HBV DNA level <2000 IU/mL identified patients whose virus remained inactive for the entire follow-up period, with 98% specificity and a positive predictive value of 97%, for all HBV genotypes. Patients with HBV activity who had levels of HBV DNA <5000 IU/mL and decreases in HBsAg of 0.5 log IU/mL or more for 1 year had a high probability of becoming carriers of inactive HBV in the next year.
  
  
  
  In a retrospective, dynamic analysis of almost 300 patients with chronic HBV infection, we found that levels of HBsAg <100 IU/mL identify patients with inactive virus with a high level of specificity. HBsAg levels should therefore be used to define phases of HBV infection in HBe antigen-negative patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands. Electronic address: w.p.brouwer@erasmusmc.nl.
authors.forename: Willem P
authors.initials: WP
authors.lastname: Brouwer
authors.affiliation: Department of Medicine & Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Henry Lik-Yuen
authors.initials: HL
authors.lastname: Chan
authors.affiliation: Hepatology Unit, University of Pisa, Pisa, Italy.
authors.forename: Maurizia R
authors.initials: MR
authors.lastname: Brunetto
authors.affiliation: Centre de Recherche Biomédicale Bichat-Beaujon, Université Paris-Diderot, Clichy, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Arends
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.affiliation: Hepatology Unit, University of Pisa, Pisa, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cherubini
authors.affiliation: St. Vincent's Hospital and the University of Melbourne, Melbourne, Australia.
authors.forename: Alex J V
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
authors.affiliation: Centre de Recherche Biomédicale Bichat-Beaujon, Université Paris-Diderot, Clichy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands; UHN Liver Clinic, Toronto Western and General Hospital, University Health Network Toronto, Toronto, Canada.
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands; Department of Public Health, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001208:Asia; D001315:Australia; D002353:Carrier State / Q000175:diagnosis*; D004279:DNA, Viral / Q000097:blood; D003955:Diagnostic Tests, Routine / Q000379:methods*; D005060:Europe; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000175:diagnosis*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D062606:Tertiary Care Centers
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D000410:Alanine Transaminase
keywords: Dynamic Prediction; HBe Antigen; HBs Antigen; Inactive Carrier