title: Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma.
abstract: OBJECTIVE
  To explore factors associated with persistent hepatitis B virus (HBV) infection in a cohort of hepatocellular carcinoma (HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen (HBsAg)-positive relatives.
  
  
  METHODS
  We evaluated non-genetic factors associated with HBV replication in relatives of patients with HCC. Relatives of 355 HCC cases were interviewed using a structured questionnaire. Demographics, relationship to index case, HBsAg status of mothers and index cases were evaluated for association with the HBV persistent infection or viral load by generalized estimating equation analysis.
  
  
  RESULTS
  Among 729 relatives enrolled, parent generation (P= 0.0076), index generation (P= 0.0044), mothers positive for HBsAg (P= 0.0007), and HBsAg-positive index cases (P= 5.98 × 10-8) were associated with persistent HBV infection. Factors associated with HBV viral load were evaluated among 303 HBsAg-positive relatives. Parent generation (P= 0.0359) and sex (P= 0.0007) were independent factors associated with HBV viral load. The intra-family HBV viral load was evaluated in families clustered with HBsAg-positive siblings. An intra-family trend of similar HBV viral load was found for 27 of 46 (58.7%) families. Male offspring of HBsAg-positive mothers (P= 0.024) and older siblings were associated with high viral load.
  
  
  CONCLUSIONS
  Sex and generation play important roles on HBV viral load. Maternal birth age and nutritional changes could be the reasons of viral load difference between generations.
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Ai-Ru
authors.initials: AR
authors.lastname: Hsieh
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Cathy Sj
authors.initials: CS
authors.lastname: Fann
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hung-Chun
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shy-Yi
authors.initials: SY
authors.lastname: Wan
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tai
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Lin
authors.affiliation: Ai-Ru Hsieh, Graduate Institute of Biostatistics, China Medical University, Taichung 40402, Taiwan.
authors.forename: Dar-In
authors.initials: DI
authors.lastname: Tai
mesh_terms: D000328:Adult; D000367:Age Factors; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics / Q000821:virology*; D015331:Cohort Studies; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics / Q000821:virology*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D035781:Siblings; D019562:Viral Load; D014779:Virus Replication
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: Familial generation; Hepatitis B virus; Perinatal infection; Sex; Viral replication