• Vishwadeep Ahluwalia, James B Wade, Douglas M Heuman, Thomas A Hammeke, Arun J Sanyal, Richard K Sterling, R Todd Stravitz, Velimir Luketic, Mohammad S Siddiqui, Puneet Puri, Michael Fuchs, Micheal J Lennon, Kenneth A Kraft, HoChong Gilles, Melanie B White, Nicole A Noble, and Jasmohan S Bajaj.
• Division of Radiology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
• Metab Brain Dis. 2014 Dec 1;29(4):1017-25.

UnlabelledMinimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE.HypothesisRifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks.MethodsCirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. RESULTS were compared before/after rifaximin.Results20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.

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