title: Serum Levels of Hepatitis B Surface Antigen Predict Severity of Fibrosis in Patients With E Antigen-Positive Chronic Hepatitis B.
abstract: OBJECTIVE
  Noninvasive techniques are needed to assess hepatic fibrosis in patients with chronic hepatitis B. We developed a scoring system to determine the degree of fibrosis in patients with genotype B or genotype C hepatitis B virus (HBV) infection and positive for the hepatitis B e antigen.
  
  
  METHODS
  We performed a retrospective study to identify baseline variables associated with the severity of fibrosis (METAVIR scores, F0-F4) in a large phase 3 clinical trial of predominantly Asian patients (n = 710), using multivariate logistic regression analyses. Significant variables were used to construct predictive models using optimal cut-off values. The final model was validated in similar patients from a large phase 4 clinical trial (n = 465).
  
  
  RESULTS
  We developed 2 prediction scoring systems (PSs). PS1 analyzed data on HBV genotype (B vs. C), patient age (<30 vs. ≥30 y), level of hepatitis B surface antigen (≤17,500 vs. >17,500 IU/mL), and level of alanine aminotransferase (≤3-fold vs. >3-fold the upper limit of normal). PS2 analyzed data on only age and level of hepatitis B surface antigen. PS1 identified patients with F0 to F1 vs. F2 to F4 fibrosis with more than 87% specificity and a positive predictive value greater than 75; it identified patients with F0 to F2 vs. F2 to F4 fibrosis with approximately 95% specificity and a positive predictive value (PPV) of approximately 97%. PS2 identified patients with F0 to F1 fibrosis with less accuracy than PS1, but identified patients with F0 to F2 fibrosis with an almost identical level of sensitivity and PPV.
  
  
  CONCLUSIONS
  We developed a simple scoring system to determine the severity of fibrosis in patients with genotypes B or C HBV infection who are hepatitis B e antigen positive. Our system differentiated patients with no or mild fibrosis (F0-F1) from those with marked or severe (F2-F4) fibrosis with a high PPV. The high level of specificity for the identification of nonsevere fibrosis (F0-F2) limits the risk of overlooking patients with severe fibrosis (F3-F4).
authors.affiliation: Centre de Recherche sur l'Inflammation, UMR 1149 Inserm, Université Paris Diderot, Clichy, France; Service d'Hépatologie, AP-HP Hôpital Beaujon, Clichy, France. Electronic address: patrick.marcellin@bjn.aphp.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Centre de Recherche sur l'Inflammation, UMR 1149 Inserm, Université Paris Diderot, Clichy, France; Service d'Hépatologie, AP-HP Hôpital Beaujon, Clichy, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.affiliation: Centre de Recherche sur l'Inflammation, UMR 1149 Inserm, Université Paris Diderot, Clichy, France; Service d'Hépatologie, AP-HP Hôpital Beaujon, Clichy, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: Roche Diagnostics Ltd, Forrenstrasse, 6343 Rotkreuz, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Batrla
authors.affiliation: IST GmbH, Mannheim, Germany.
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.affiliation: IST GmbH, Mannheim, Germany.
authors.forename: Vivien
authors.initials: V
authors.lastname: Rothe
authors.affiliation: Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China; Humanity and Health Gastroenterology and Liver Clinic, Hong Kong SAR, China.
authors.forename: George
authors.initials: G
authors.lastname: Lau
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
mesh_terms: D000328:Adult; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D017326:Clinical Trials, Phase III as Topic; D003661:Decision Support Techniques; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D015233:Models, Statistical; D012189:Retrospective Studies; D044967:Serum / Q000821:virology; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens
keywords: CHB; Diagnostics; Liver Disease; Serum Biomarker