title: Changes of HBsAg and interferon-inducible protein 10 serum levels in naive HBeAg-negative chronic hepatitis B patients under 4-year entecavir therapy.
abstract: OBJECTIVE
  Serum HBsAg levels might represent an important predictor of sustained off-treatment response in HBeAg-negative chronic hepatitis B (CHB). We evaluated the changes of HBsAg and interferon-inducible protein 10 (IP10) serum levels in HBeAg-negative CHB patients treated with entecavir.
  
  
  METHODS
  114 patients received entecavir for a median of 4.3 years. HBsAg levels were determined at baseline, 6 and 12 months and every year thereafter until year-4. IP10 levels were measured at baseline and annually until year-4 in 76 patients.
  
  
  RESULTS
  Virological remission rates were high (year-1: 94%, after year-2: 97-98%). Compared to baseline, HBsAg levels decreased by a median of 0.03, 0.13, 0.17, 0.22, and 0.32 log₁₀ IU/ml at 6 months and 1, 2, 3, and 4 years, respectively (p≤0.001 for all comparisons). The proportions of patients with HBsAg decline of ≥0.5 or ≥1 log₁₀ IU/ml were 9% or 6% at year-1 and 21% or 10% at the last visit. Median IP10 levels (pg/ml) did not change from baseline to year-1 or -2 (245 vs. 229 or 251), but increased at year-3 and -4 (275 and 323, p<0.030). HBsAg drop ≥0.5 log₁₀ was associated with baseline IP10 or IP10 >350 pg/ml (p≤0.002). HBsAg loss occurred in 4/114 (3.5%) patients or in 1/2, 3/21, and 0/91 patients with baseline HBsAg <100, 100-1000 and >1000 IU/ml, respectively (p<0.001).
  
  
  CONCLUSIONS
  In HBeAg-negative CHB patients, 4-year entecavir therapy decreases serum HBsAg levels, but the rate of decline is rather slow. Serum IP10 levels represent a promising predictor of HBsAg decline in this setting.
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokration Hospital of Athens, Greece; Academic Department of Gastroenterology, Athens University Medical School, Laikon Hospital of Athens, Greece. Electronic address: gepapath@med.uoa.gr.
authors.forename: George
authors.initials: G
authors.lastname: Papatheodoridis
authors.affiliation: 4th Department of Medicine, Aristotelian University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Goulis
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokration Hospital of Athens, Greece.
authors.forename: Spilios
authors.initials: S
authors.lastname: Manolakopoulos
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokration Hospital of Athens, Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Margariti
authors.affiliation: 4th Department of Medicine, Aristotelian University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Greece.
authors.forename: Xenofon
authors.initials: X
authors.lastname: Exarchos
authors.affiliation: 4th Department of Medicine, Aristotelian University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kokkonis
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokration Hospital of Athens, Greece.
authors.forename: Emilia
authors.initials: E
authors.lastname: Hadziyiannis
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokration Hospital of Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Papaioannou
authors.affiliation: Athens University Medical School, Greece.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Manesis
authors.affiliation: 2nd Department of Internal Medicine, Athens University Medical School, Hippokration Hospital of Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.affiliation: 4th Department of Medicine, Aristotelian University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Akriviadis
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D054357:Chemokine CXCL10 / Q000097:blood*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models
chemical_list: D000998:Antiviral Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine
keywords: ALT; Entecavir; HBV; HBeAg; HBsAg; Hepatitis B; IQR; Interferon-inducible protein 10; LSM; NA(s); PCR; SD; ULN; alanine aminotransferase; anti-HBe; antibody against HBeAg; hepatitis B e antigen; hepatitis B surface antigen; hepatitis B virus; interquartile range; liver stiffness measurement; nucleos(t)ide analogue(s); polymerase chain reaction; standard deviation; upper limit of normal