title: Progression to cirrhosis, hepatocellular carcinoma and liver-related mortality in chronic hepatitis B patients in Italy.
abstract: BACKGROUND
  The natural history of chronic hepatitis B is variable. We evaluated some of the risk factors for cirrhosis, hepatocellular carcinoma and liver-related mortality in Italian patients with chronic hepatitis B.
  
  
  METHODS
  A cohort of 105 untreated patients with chronic hepatitis B without cirrhosis at diagnosis was followed prospectively for a mean period of 23 years. Clinical, histological and ultrasound examinations, biochemical and virological tests, and causes of death were analyzed.
  
  
  RESULTS
  Forty-two (40%) patients became inactive carriers and 63 (60%) showed persistent alanine aminotransferase elevation: 13 (13%) associated with HBeAg persistence, 35 (33%) with detectable serum HBV-DNA but HBeAg-negative, 11 (10%) with concurrent virus infection and 4 (4%) with non-alcoholic fatty liver disease. Cirrhosis incidence was 1.56/100 person-years. Older age and sustained HBV replication predicted cirrhosis occurrence independently. Hepatocellular carcinoma incidence was 2.1/100 person-years in patients who developed cirrhosis and 0.06 in those who did not. Cirrhosis occurrence was associated with an increased risk of hepatocellular carcinoma (hazard ratio 20.4, 95% confidence interval 2.54-167.5) and liver-related death (16.5, 2.0-138.8).
  
  
  CONCLUSIONS
  In Italian patients with chronic hepatitis B cirrhosis strongly predicts hepatocellular carcinoma occurrence and disease-related mortality, thus indicating that early antiviral treatment should be instituted before cirrhosis occurrence.
authors.affiliation: Division of Gastroenterology and Endoscopy, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Department of Surgery, University of Verona, Verona, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Ieluzzi
authors.affiliation: Institute of Hygiene, Epidemiology and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Covolo
authors.affiliation: Institute of Hygiene, Epidemiology and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Donato
authors.affiliation: Division of Gastroenterology and Endoscopy, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; Department of Medicine, University of Verona, Verona, Italy. Electronic address: giovanna.fattovich@univr.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Fattovich
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000821:virology; D002353:Carrier State / Q000097:blood / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000235:genetics / Q000401:mortality*; D018937:Hepatitis C Antibodies / Q000097:blood; D003699:Hepatitis D / Q000276:immunology; D006801:Humans; D015994:Incidence; D007378:Interleukins / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008103:Liver Cirrhosis / Q000401:mortality* / Q000821:virology; D008113:Liver Neoplasms / Q000401:mortality* / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D014779:Virus Replication; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D018937:Hepatitis C Antibodies; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: Chronic hepatitis B; Cirrhosis; Hepatocellular carcinoma; Liver-related mortality; Natural history