title: Relationship between level of hepatitis B virus DNA and liver disease: a population-based study of hepatitis B e antigen-negative persons with hepatitis B.
abstract: OBJECTIVE
  There is little information on the proportion of persons with chronic hepatitis B virus (HBV) infection with active hepatitis. We aimed to determine the proportion of persons with hepatitis B e antigen-negative chronic HBV infection who develop immune-active HBV infection over time and the relationship between demographic and viral factors on severity of disease on liver biopsy.
  
  
  METHODS
  We performed a longitudinal population-based cohort study of 754 Alaska Native patients with chronic HBV infection. Levels of alanine aminotransferase (ALT) were measured every 6 months, and levels of HBV DNA were measured at study entry and whenever ALT levels exceeded the upper limit of normal (ULN). Immune-active chronic HBV infection was defined as levels of ALT ≥ 30 U/L in men and >20 U/L in women and levels of HBV DNA >2000 IU/mL at 1 or more time points from 2001-2008. Liver biopsies were scored by using the modified histology activity index score of Knodell and the Ishak fibrosis score.
  
  
  RESULTS
  Of the study participants, 186 (25%) met the criteria for immune-active HBV, 56% of these initially and 44% later during follow up. Of the 38 patients with liver biopsy results, only 1 of 16 with ALT levels consistently below twice the ULN and 1 of 19 with HBV DNA between 2000 and 20,000 IU/mL, vs 12 of 22 (55%) with ALT > twice ULN (P = .002) and 11 of 18 (61%) with 1 or more measurements of HBV DNA >20,000 IU/mL (P < .001), had moderate or severe hepatitis or fibrosis.
  
  
  CONCLUSIONS
  In a cohort of Alaska Natives with chronic HBV infection, 25% met criteria for immune-active HBV. There is a low probability of advanced fibrosis if levels of HBV DNA never exceed 20,000 IU/mL.
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska; Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Anchorage, Alaska.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McMahon
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC), Anchorage, Alaska.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bulkow
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Brenna
authors.initials: B
authors.lastname: Simons
authors.affiliation: Division of Gastroenterology/Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Susan
authors.initials: S
authors.lastname: Negus
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Chriss
authors.initials: C
authors.lastname: Homan
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.
authors.forename: Philip
authors.initials: P
authors.lastname: Spradling
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.
authors.forename: Eyasu
authors.initials: E
authors.lastname: Teshale
authors.affiliation: Division of Gastroenterology/Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Daryl
authors.initials: D
authors.lastname: Lau
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
authors.forename: Mary
authors.initials: M
authors.lastname: Snowball
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska. Electronic address: slivings@anthc.org.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Livingston
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000413:Alaska; D001706:Biopsy; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006511:Hepatitis B Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000473:pathology* / Q000821:virology*; D006651:Histocytochemistry; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006511:Hepatitis B Antigens; D000410:Alanine Transaminase
keywords: HBV Genotype; HBsAg; Liver Biopsy
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