title: Chronic hepatitis B: recommendations for therapy based on the natural history of disease in Australian patients.
abstract: BACKGROUND
  Chronic hepatitis B infection (CHB) is a major health problem in Australia and worldwide. CHB is associated with significant long-term morbidity and mortality. Well tolerated treatment is now available, however the development of resistance is common and the optimal timing of treatment is yet to be determined. Identifying the factors that influence the natural history of CHB may help determine which patients need treatment and when to start it.
  
  
  OBJECTIVE
  To determine the demographics, clinical features and virological profile of Australian patients infected with CHB and the influence of these factors on disease activity and severity.
  
  
  METHODS
  Review of prospectively collected demographic, clinical and virological features of all patients positive for hepatitis B surface antigen (HBsAg) for more than 6 months who were referred to St. Vincent's Hospital liver clinics. Age, sex and ethnicity were correlated with hepatitis B e antigen status (HBeAg), HBV replication status (ALT and HBV DNA), genotype and liver histology.
  
  
  RESULTS
  703 chronic hepatitis B surface antigen positive patients were identified. The patients were predominantly male with an average age of 44. Eighty two percent of patients were born overseas, primarily from Asian (65%) and Mediterranean countries (14%). Two thirds (426) had an elevated ALT (median 79) at presentation. HBeAg was positive in 37%. Active viral replication, defined as abnormal ALT or positive HBVDNA, was present in 74%, 48% of whom were HBeAg negative. In a subset of 103 patients genotyped, 8% had genotype A, 29% B, 41% C and 22% D. Genotype correlated with ethnicity; patients infected with genotypes A were predominantly Caucasian, B and C were Asian, and D were Mediterranean. Of 296 (42%) patients who underwent liver biopsy, 76 (27%) had advanced fibrosis. Advanced fibrosis was associated with increasing age and Mediterranean ethnicity.
  
  
  CONCLUSIONS
  Perinatal or early childhood transmission is predominant mode of infection in Australia. Two thirds of this cohort had active replication and were at increased risk of developing cirrhosis and/or hepatoma. Advanced disease was associated with age and ethnicity. HBeAg negative CHB accounts for almost half of all those with active viral replication. This parallels the rise in this form of CHB in Asia and the Mediterranean basin. Screening should be offered to people born in, or with parents born in areas of high endemnicity. To detect the development of active disease, patients with positive HBsAg but normal ALT should have liver function tests done 6 monthly and those with elevated ALT should be referred for consideration of therapy, irrespective of HBeAg status.
authors.affiliation: Department of Gastroenterology, St. Vincent's Hospital, P.O. Box 2900, Fitzroy 3065, Australia. bells@svhm.org.au
authors.forename: S J
authors.initials: SJ
authors.lastname: Bell
authors.forename: A
authors.initials: A
authors.lastname: Lau
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: K J R
authors.initials: KJ
authors.lastname: Watson
authors.forename: B
authors.initials: B
authors.lastname: Demediuk
authors.forename: G
authors.initials: G
authors.lastname: Shaw
authors.forename: R Y
authors.initials: RY
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Ayres
authors.forename: L
authors.initials: L
authors.lastname: Yuen
authors.forename: A
authors.initials: A
authors.lastname: Bartholomeusz
authors.forename: S A
authors.initials: SA
authors.lastname: Locarnini
authors.forename: P V
authors.initials: PV
authors.lastname: Desmond
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001315:Australia / Q000453:epidemiology; D003710:Demography; D005006:Ethnicity; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D008297:Male; D012720:Severity of Illness Index
chemical_list: D000998:Antiviral Agents