Review article: potential mechanisms of action of rifaximin in the management of hepatic encephalopathy and other complications of cirrhosis

Abstract

Background: Progressive gut milieu (microbiota) changes occur in patients with cirrhosis and are associated with complications [e.g. hepatic encephalopathy (HE)].

Aim: To examine the role of rifaximin in the management of HE and other complications of cirrhosis, including potential mechanisms of action and the need for future studies.

Methods: A literature search was conducted using the keywords 'rifaximin', 'hepatic encephalopathy', 'ascites', 'variceal bleeding', 'peritonitis', 'portal hypertension', 'portopulmonary hypertension' and 'hepatorenal syndrome'.

Results: The nonsystemic agent rifaximin reduces the risk of HE recurrence and HE-related hospitalisations in cirrhosis. In patients with cirrhosis, rifaximin modulates the bacterial composition of the gut microbiota without a consistent effect on overall faecal microbiota composition. However, rifaximin can impact the function or activities of the gut microbiota. For example, rifaximin significantly increased serum levels of long-chain fatty acids and carbohydrate metabolism intermediates in patients with minimal HE. Rifaximin also favourably affects serum proinflammatory cytokine and faecal secondary bile acid levels.

Conclusions: The gut microenvironment and associated microbiota play an important role in the pathogenesis of HE and other cirrhosis-related complications. Rifaximin's clinical activity may be attributed to effects on metabolic function of the gut microbiota, rather than a change in the relative bacterial abundance.