title: Changes in liver histology as a "surrogate" end point of antiviral therapy for chronic HBV can predict progression to liver complications.
abstract: BACKGROUND
  The modified histology activity index (HAI) score has been extensively used as an additional primary or secondary end point in most phase III pivotal therapeutic clinical trials on chronic hepatitis B. Improvement in modified HAI after antiviral therapy has usually been defined as a 2-point reduction in modified HAI score.
  
  
  OBJECTIVE
  We studied whether a 2-point change in modified HAI score after antiviral therapy for chronic hepatitis B is associated with progression to liver complications (decompensated cirrhosis or hepatocellular carcinoma).
  
  
  METHODS
  Eighty-nine patients treated with interferon-alpha with liver biopsy before and at 6 to 12 months after the end of therapy were followed-up for a median 119.4 months.
  
  
  RESULTS
  At the time of analysis, 11 patients (12.4%) had liver complications. Liver complications were higher in patients with a 2-point increase in modified HAI score [8 of 19 patients (42.1%) vs. 3 of 70 patients (4.3%), P=0.0002] and in those with severe fibrosis at end of therapy [6 of 19 patients (31.6%) vs. 5 of 70 patients (7.1%), P=0.010]. On Cox regression analysis, a 2-point increase in modified HAI score was associated with increased liver complications (relative risk 5.564, P=0.036).
  
  
  CONCLUSIONS
  A 2-point increase in modified HAI score after antiviral therapy is associated with increased progression to liver complications.
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong SAR, China. ckhui23@gmail.com
authors.forename: Chee-Kin
authors.initials: CK
authors.lastname: Hui
authors.forename: Nancy
authors.initials: N
authors.lastname: Leung
authors.forename: Wai-Hung
authors.initials: WH
authors.lastname: Shek
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zhang
authors.forename: John M
authors.initials: JM
authors.lastname: Luk
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Chung-Mau
authors.initials: CM
authors.lastname: Lo
authors.forename: Sheung-Tat
authors.initials: ST
authors.lastname: Fan
authors.forename: George K K
authors.initials: GK
authors.lastname: Lau
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006510:Hepatitis B Antibodies / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006513:Hepatitis B e Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens