title: Large variations in risk of hepatocellular carcinoma and mortality in treatment naïve hepatitis B patients: systematic review with meta-analyses.
abstract: BACKGROUND
  The complications to chronic hepatitis B (HBV) include incidence of hepatocellular carcinoma (HCC) and mortality. The risk of these complications may vary in different patient groups.
  
  
  OBJECTIVE
  To estimate the incidence and predictors of HCC and in untreated HBV patients.
  
  
  METHODS
  Systematic review with random effects meta-analyses of randomized controlled trials and observational studies. Results are expressed as annual incidence (events per 100 person-years) with 95% confidence intervals. Subgroup and sensitivity analyses of patient and study characteristics were performed to identify common risk factors.
  
  
  RESULTS
  We included 68 trials and studies with a total of 27,584 patients (264,919 person-years). In total, 1,285 of 26,687 (5%) patients developed HCC and 730 of 12,511 (6%) patients died. The annual incidence was 0.88 (95% CI, 0.76-0.99) for HCC and 1.26 (95% CI, 1.01-1.51) for mortality. Patients with cirrhosis had a higher risk of HCC (incidence 3.16; 95% CI, 2.58-3.74) than patients without cirrhosis (0.10; 95% CI, 0.02-0.18). The risk of dying was also higher for patients with than patients without cirrhosis (4.89; 95% CI, 3.16-6.63; and 0.11; 95% CI, 0.09-0.14). The risk of developing HCC increased with HCV coinfection, older age and inflammatory activity. The country of origin did not clearly predict HCC or mortality estimates.
  
  
  CONCLUSIONS
  Cirrhosis was the strongest predictor of HCC incidence and mortality. Patients with HBV cirrhosis have a 31-fold increased risk of HCC and a 44-fold increased mortality compared to non-cirrhotic patients. The low incidence rates should be taken into account when considering HCC screening in non-cirrhotic patients.
  
  
  BACKGROUND
  Prospero CRD42013004764.
authors.affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
authors.forename: Maja
authors.initials: M
authors.lastname: Thiele
authors.affiliation: Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Lise Lotte
authors.initials: LL
authors.lastname: Gluud
authors.affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
authors.forename: Annette Dam
authors.initials: AD
authors.lastname: Fialla
authors.affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
authors.forename: Emilie Kirstine
authors.initials: EK
authors.lastname: Dahl
authors.affiliation: Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
mesh_terms: D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality*; D060085:Coinfection; D019694:Hepatitis B, Chronic / Q000150:complications*; D006526:Hepatitis C; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000209:etiology; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality*; D012306:Risk; D044465:White People