The Use of Rifaximin in Patients With Cirrhosis

Abstract

Rifaximin is an oral nonsystemic antibiotic with minimal gastrointestinal absorption and broad-spectrum antibacterial activity covering both gram-positive and gram-negative organisms. Rifaximin is currently used worldwide in patients with cirrhosis for preventing recurrent HE because its efficacy and safety have been proven by large randomized clinical trials. In the last decade, experimental and clinical evidence suggest that rifaximin could have other beneficial effects on the course of cirrhosis by modulating the gut microbiome and affecting the gut-liver axis, which in turn can interfere with major events of the pathophysiological cascade underlying decompensated cirrhosis, such as systemic inflammatory syndrome, portal hypertension, and bacterial infections. However, the use of rifaximin for prevention or treatment of other complications, including spontaneous bacterial peritonitis or other bacterial infections, is not accepted because evidence by clinical trials is still very weak. The present review deals in the first part with the potential impact of rifaximin on pathogenic mechanisms in liver diseases, whereas in the second part, its clinical effects are critically discussed. It clearly emerges that, because of its potential activity on multiple pathogenic events, the efficacy of rifaximin in the prevention or management of complications other than HE deserves to be investigated extensively. The results of double-blinded, adequately powered randomized clinical trials assessing the effect of rifaximin, alone or in combination with other drugs, on hard clinical endpoints, such as decompensation of cirrhosis, acute-on-chronic liver failure, and mortality, are therefore eagerly awaited.

FIG. 1

Molecular structure of rifaximin and rifampicin.

FIG. 2

Putative effects of rifaximin on the gut‐liver axis. Rifaximin was shown to increase intestinal epithelial homeostasis by PXR‐dependent mechanisms. Among them, inhibition of NF‐κB; decrease of TNF‐α, IL‐6, IL‐8, and IL‐10 secretion; and induction of biotransformation phase 1 and 2 enzyme activities (e.g., cytochrome P450 3A4 [CYP3A4], glutathione S‐transferase alpha 1 [GSTA‐1]) are notable. Subtle changes in intestinal microbiome composition and lowering of virulence factors have also been observed. Effects of rifaximin on bacterial bile acid biotransformation are yet unclear. Rifaximin led to normalization of serum LPS binding protein levels and thereby lowering of the proinflammatory state in the liver. Figure created with Biorender.com. Abbreviation: RXR, retinoid X receptor.