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. AIMS: 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.
RCT Entities:
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. AIMS: 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: Oluyemi Komolafe; Danielle Roberts; Suzanne C Freeman; Peter Wilson; Alex J Sutton; Nicola J Cooper; Chavdar S Pavlov; Elisabeth Jane Milne; Neil Hawkins; Maxine Cowlin; Douglas Thorburn; Brian R Davidson; Emmanuel Tsochatzis; Kurinchi Selvan Gurusamy Journal: Cochrane Database Syst Rev Date: 2020-01-16