title: Norfloxacin treatment for clinically significant portal hypertension: results of a randomised double-blind placebo-controlled crossover trial.
abstract: BACKGROUND
  While selective intestinal decontamination (SID) can alter the hyperdynamic circulatory state of cirrhosis, the impact of SID on portal pressure remains unclear especially in the setting of clinically significant portal hypertension.
  
  
  OBJECTIVE
  To examine the impact of SID with norfloxacin on portal pressure in subjects with clinically significant portal hypertension and explore the potential mechanisms by which norfloxacin exerts its haemodynamic effects.
  
  
  METHODS
  Randomised, double blind, placebo-controlled, crossover trial of norfloxacin 400 mg twice daily for 4 weeks. The portal pressure was assessed by hepatic venous pressure gradient (HVPG). Endotoxaemia was assessed by the Limulus amebocyte lysate (LAL) assay. l-arginine (l-Arg) transporter function was assessed in peripheral blood mononuclear cells (PBMCs). Plasma levels of urotensin II (UII) and tumour necrosis factor were measured before and after therapy.
  
  
  RESULTS
  Sixteen subjects with clinically significant portal hypertension (16.5+/-1.1 mmHg) completed the study. Norfloxacin therapy was not superior to placebo in reducing HVPG (13.8+/-1.0 mmHg vs 13.6+/-1.2 mmHg, P=0.3). Furthermore, no alteration in l-Arg transport was detected after 4 weeks of norfloxacin therapy. Plasma UII levels correlated positively with HVPG (P=0.01) and the Child-Pugh score (P<0.05). However, UII levels following therapy did not parallel HVPG changes.
  
  
  CONCLUSIONS
  Norfloxacin is not superior to placebo in reducing HVPG in subjects with clinically significant portal hypertension. Furthermore, norfloxacin does not appear to modulate the l-Arg transporter mechanism in this patient population. Although plasma UII correlates positively with HVPG, UII does not appear to have a direct role in modulating HVPG.
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. w.kemp@alfred.org.au
authors.forename: William
authors.initials: W
authors.lastname: Kemp
authors.forename: John
authors.initials: J
authors.lastname: Colman
authors.forename: Kenneth
authors.initials: K
authors.lastname: Thompson
authors.forename: Anoop
authors.initials: A
authors.lastname: Madan
authors.forename: Margaret
authors.initials: M
authors.lastname: Vincent
authors.forename: Jaye
authors.initials: J
authors.lastname: Chin-Dusting
authors.forename: Andrew
authors.initials: A
authors.lastname: Kompa
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Stuart
authors.initials: S
authors.lastname: Roberts
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000378:metabolism*; D018592:Cross-Over Studies; D019446:Endotoxemia / Q000188:drug therapy*; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy*; D008103:Liver Cirrhosis / Q000382:microbiology*; D009643:Norfloxacin / Q000494:pharmacology* / Q000627:therapeutic use; D017082:Portal Pressure / Q000187:drug effects*; D018709:Statistics, Nonparametric; D014579:Urotensins / Q000097:blood; D014739:Victoria
chemical_list: D000900:Anti-Bacterial Agents; D014579:Urotensins; C029677:urotensin II; D001120:Arginine; D009643:Norfloxacin