Bacterial infection in the pathogenesis of variceal bleeding

Lancet. 1999 Jan 9;353(9147):139-42. doi: 10.1016/S0140-6736(98)06020-6.


Variceal bleeding is a life-threatening complication of cirrhosis. Potential risk factors include clinical, endoscopic, and haemodynamic factors, but why bleeding occurs unpredictably in individual patients is not known. We postulate that bacterial infections in patients with variceal haemorrhage may be the critical factor that triggers bleeding. In patients with large varices and a high wall tension, the release of endotoxin into the systemic circulation during episodes of bacterial infection results in a further increase in portal pressure through the induction of endothelin and possibly vasoconstrictive cyclo-oxygenase products. The subsequent contraction of hepatic stellate cells causes a rise in intrahepatic vascular resistance. Furthermore, endotoxin-induced nitric oxide and prostacyclin, and prostacyclin induced by endothelin could inhibit platelet aggregation, which may result in a further deterioration of primary haemostasis at the level of varix. We propose that the combination of these two effects leads to the onset of variceal haemorrhage.

MeSH terms

  • Bacterial Infections / microbiology*
  • Bacterial Infections / physiopathology
  • Endothelins / physiology
  • Endotoxins / blood*
  • Esophageal and Gastric Varices / microbiology*
  • Esophageal and Gastric Varices / physiopathology
  • Gastrointestinal Hemorrhage / microbiology*
  • Gastrointestinal Hemorrhage / physiopathology
  • Hemostasis / physiology
  • Humans
  • Liver / blood supply
  • Nitric Oxide / physiology
  • Portal Pressure / physiology
  • Risk Factors
  • Vascular Resistance / physiology


  • Endothelins
  • Endotoxins
  • Nitric Oxide