title: Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial.
abstract: OBJECTIVE
  To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women.
  
  
  METHODS
  Prospective, randomised, double blind, placebo controlled trial.
  
  
  METHODS
  5408 healthy women who had had hysterectomies, recruited into the Italian tamoxifen chemoprevention trial from 58 centres in Italy.
  
  
  METHODS
  Women were randomly assigned to receive tamoxifen (20 mg daily) or placebo for five years.
  
  
  METHODS
  Development of non-alcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine aminotransferase (> or = 1.5 times upper limit of normal) over a six month period.
  
  
  RESULTS
  During follow up, 64 women met the predefined criteria: 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo)--hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P = 0.04). In all 52 women ultrasonography confirmed the presence of fatty liver. Other factors associated with the development of non-alcoholic fatty liver disease included overweight (2.4, 1.2 to 4.8), obesity (3.6, 1.7 to 7.6), hypercholesterolaemia (3.4, 1.4 to 7.8), and arterial hypertension (2.0, 1.0 to 3.8). Twenty women had liver biopsies: 15 were diagnosed as having mild to moderate steatohepatitis (12 tamoxifen, 3 placebo), and five had fatty liver alone (1 tamoxifen, 4 placebo). No clinical, biochemical, ultrasonic, or histological signs suggestive of progression to cirrhosis were observed after a median follow up of 8.7 years.
  
  
  CONCLUSIONS
  Tamoxifen was associated with higher risk of development of non-alcoholic steatohepatitis only in overweight and obese women with features of metabolic syndrome, but the disease, in both the tamoxifen and the placebo group, after 10 years of follow up seems to be indolent.
authors.affiliation: Liver Unit, Azienda Ospedaliera Fatebenefratelli e Oftalmico, Corso di Porta Nuova 23, 20121 Milan, Italy. savino.bruno@fbf.milano.it
authors.forename: Savino
authors.initials: S
authors.lastname: Bruno
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Paola
authors.initials: P
authors.lastname: Castellana
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotmensz
authors.forename: Sonia
authors.initials: S
authors.lastname: Rossi
authors.forename: Marco
authors.initials: M
authors.lastname: Maggioni
authors.forename: Marcello
authors.initials: M
authors.lastname: Persico
authors.forename: Alberto
authors.initials: A
authors.lastname: Colombo
authors.forename: Franco
authors.initials: F
authors.lastname: Monasterolo
authors.forename: Donata
authors.initials: D
authors.lastname: Casadei-Giunchi
authors.forename: Franco
authors.initials: F
authors.lastname: Desiderio
authors.forename: Tommaso
authors.initials: T
authors.lastname: Stroffolini
authors.forename: Virgilio
authors.initials: V
authors.lastname: Sacchini
authors.forename: Andrea
authors.initials: A
authors.lastname: Decensi
authors.forename: Umberto
authors.initials: U
authors.lastname: Veronesi
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001706:Biopsy / Q000379:methods; D001943:Breast Neoplasms / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004311:Double-Blind Method; D005234:Fatty Liver / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008099:Liver / Q000473:pathology; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013629:Tamoxifen / Q000009:adverse effects*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen
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