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

Summary 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.