Effect of poorly absorbable antibiotics on hepatic venous pressure gradient in cirrhosis: A systematic review and meta-analysis

Background: The effects of poorly/non-absorbable antibiotics on hepatic venous pressure gradient (HVPG) are debated. Aim: To analyze the effects of rifaximin or norfloxacin on HVPG and on markers of bacterial translocation and proinflammatory cytokines. Methods: We performed a systematic search of randomized clinical trials (RCTs) involving patients with cirrhosis and portal hypertension, assessing the effect of rifaximin or norfloxacin vs control on HVPG. Pooled analyses were based on random-effects models, heterogeneity was assessed by Cochran's Q, I-2 statistic and subgroup analyses. Results: Five studies (215 patients) were included. Risk of bias was high in three. We found no significant differences using antibiotics versus control. The summary mean difference in HVPG was of -0.55 mmHg (95%CI:-1.52, 0.42; P = 0.27), with moderate heterogeneity (P = 0.15; I-2 = 40%). RCTs with longer therapy (60-90 days) used non-selective-beta-blockers (NSBB) in both antibiotics and control arms. Subgroup analysis showed a significantly greater reduction in HVPG in the combination arm over controls (mean difference -1.46 mmHg [95%CI: -2.63, -0.28; P = 0.01]) with no heterogeneity (P = 0.46; I-2 = 0%). Serum lipopolysaccharide-binding protein (LBP) significantly decreased with antibiotics, but with high heterogeneity (P < 0.001; I-2 = 92%). Conclusions: Rifaximin or norfloxacin did not significantly reduce HVPG in patients with cirrhosis and portal hypertension. Studies using antibiotic for longer periods on top of NSBB showed a significant decrease in HVPG. (C) 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.