title: Nested case-control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance.
abstract: Hepatocellular carcinoma (HCC) risk after resolving chronic hepatitis B virus (HBV) infection is unclear.
  
  
  
  To compare HCC risk between Alaska Native (AN) patients with and without hepatitis B surface antigen (HBsAg) seroclearance.
  
  
  
  We selected persons with (case-patients) and without (control-patients) HBsAg seroclearance from a cohort of 1346 chronically HBV-infected AN patients followed during 1982-2013. We attempted to match two control-patients/case-patient on sex, HBV genotype, and age. Person-years of follow-up for case-patients began on the date of HBsAg resolution and for control-patients began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case-patient. We compared HCC risk using a Cox proportional hazards model.
  
  
  
  The 238 case-patients (4 with HCC) and 435 control-patients (9 with HCC) were similar in age [P-value (P) = 0.30], sex (P = 0.53) and HBV genotype (P = 0.99). Case-patients had longer person-years of follow-up than control-patients (11.7 vs. 10.1 years; P = 0.04). The HCC rate/100 000 persons was similar between case- (132) and control-patients (178; P = 0.65). The adjusted hazard ratio comparing case- and control-patients was similar for HCC [0.7; 95% confidence interval (CI): 0.2-2.4], increased for each 1-year increment for age (1.1; CI: 1.0-1.1; P < 0.01), and was greater if the initial HBeAg was positive (3.5; CI: 1.1-11.0; P = 0.03).
  
  
  
  Hepatitis B surface antigen seroclearance was not associated with reduced HCC risk; the HCC risk estimates are limited by wide 95% confidence intervals. Persons meeting HCC surveillance indications prior to HBsAg seroclearance could benefit from continued surveillance after seroclearance.
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention (CDC), Anchorage, AK, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Gounder
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention (CDC), Anchorage, AK, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Bulkow
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA.
authors.forename: M
authors.initials: M
authors.lastname: Snowball
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA.
authors.forename: S
authors.initials: S
authors.lastname: Negus
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Spradling
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Simons
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention (CDC), Anchorage, AK, USA.|Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: McMahon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk; D055815:Young Adult
chemical_list: D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens