title: Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia.
abstract: BACKGROUND
  Factors other than acid may play a role in gastro-oesophageal reflux disease (GERD) and its complications.
  
  
  OBJECTIVE
  To assessed the role of bile acids in the pathogenesis of GERD, Barrett's oesophagus and Barrett's-related neoplasia.
  
  
  METHODS
  We conducted a systematic review of computerised bibliographic databases for original articles involving humans or human oesophageal tissue or cells that assessed exposure to or manipulation of bile acids. Outcomes assessed included GERD symptoms; gross oesophageal injury; Barrett's oesophagus and related neoplasia; and intermediate markers of inflammation, proliferation or neoplasia.
  
  
  RESULTS
  Eighty-three original articles were included. In in vivo studies, bile acids concentrations were higher in the oesophageal aspirates of patients with GERD than controls, and bile acids infusions triggered GERD symptoms, especially in high concentrations or in combination with acid. In ex vivo/in vitro studies, bile acids stimulated squamous oesophageal cells and Barrett's epithelial cells to produce inflammatory mediators (e.g., IL-8 and COX-2) and caused oxidative stress, DNA damage and apoptosis. They also induced squamous cells to change their gene expression pattern to resemble intestinal-type cells and caused Barrett's cells to increase expression of intestinal-type genes.
  
  
  CONCLUSIONS
  In aggregate, these studies suggest that bile acids may contribute to the pathogenesis of symptoms, oesophagitis and Barrett's metaplasia with related carcinogenesis in patients with GERD. However, all study results are not uniform and substantial differences in study parameters may explain at least some of this variation.
authors: Veterans Affairs Medical Center and Department of Medicine, University of California, San Francisco, CA 94121, USA. kenneth.mcquaid@va.gov
authors: K R
authors: KR
authors: McQuaid
authors: L
authors: L
authors: Laine
authors: M B
authors: MB
authors: Fennerty
authors: R
authors: R
authors: Souza
authors: S J
authors: SJ
authors: Spechler