Background

Our intestines are host to many bacteria and the complex relationship that we have with them remains incompletely understood. For many reasons research in this area is notoriously difficult. Firstly there are lots of bacteria and of differing types, indeed there are ten times more bacterial cells in our colon than there are human cells in our body. Secondly the amount and proportions of each bacteria changes over time dependent on food, health, antibiotic use etc. Finally, to make matters harder we are not able to culture or identify a proportion of these intestinal bacteria.

Despite these difficulties there have been advances made in this field. Recent research has shown that in certain situations altering colonic bacteria can improve health. Rifaximin is an antibiotic that is virtually unabsorbed into the body after oral administration. So it remains within the intestines where it alters gut bacterial patterns and content, whilst having few systemic effects.

Patients with end-stage liver disease, or cirrhosis, have impaired liver function. One of the key activities of the liver is to detoxify the blood of bacterial-derived toxins absorbed from the intestines. In cirrhosis this detoxifying function is impaired and hence the brain of cirrhotic patients is exposed to a high level of toxins. This toxic exposure results in an impaired cognitive ability with drowsiness and confusion. This is termed hepatic encephalopathy (HE). HE varies in its severity. In an advanced form it can significantly impair quality of life and result in hospital admissions. Minimal HE is a mild or early form such that on basic tests the patients appear to function normally. Though there is clear impairment if patients undergo a rigorous cognitive assessment. Minimal HE is relatively common in cirrhosis and such patients are at risk of falls and of developing more marked HE.

Current research

In the last 3 months 2 related studies have been published on the use of rifaximin in minimal HE.

A group from Wisconsin, USA, assessed the effects of rifaximin or placebo in minimal HE patients on their performance in a car driving simulator. This was a fascinating and highly relevant paper as all the patients enrolled were currently driving. There was clear evidence of an improved driving safety with the rifaximin and these patients also reported improved psycho-social functioning.

A group from Ludhiana, India, has also assessed the effects of 8 weeks of rifaximin or placebo on psychological assessments of quality of life and cognitive function in minimal HE. There was a marked improvement with rifaximin.

Comments

These studies are highly encouraging as HE is a disabling condition with currently very limited therapy options. However if rifaximin were to be used in routine clinical practice then it would have to be used long-term as opposed to for just 8 weeks as in these studies. Rifaximin appears to be a safe and well tolerated drug, though concerns naturally exist about the side effects of long-term antibiotic therapy.

Areas for future research

We need to understand better the outcomes and safety of long-term rifaximin therapy. Ideally we should be able to alter gut bacteria in a more targeted way than the blunderbuss that is antibiotics. There therefore is a need to gain further understanding into gut bacteria, their toxins, the liver and the brain.