Rifaximin Improves Cognitive Performance in Covert Hepatic Encephalopathy

Key Takeaways

• Rifaximin was associated with significant within-group improvement on the Stroop test over 12 weeks in this randomized trial.
• The between-group change favored rifaximin overall and remained at trend level, while a baseline subgroup without synthetic disaccharides showed greater improvement.
• NCT-B scores and serum ammonia did not change significantly, cirrhosis-related adverse events were lower, and overall microbial diversity was similar between groups.

In patients with covert hepatic encephalopathy and liver cirrhosis, rifaximin was associated with significant within-group improvement on the Stroop test over 12 weeks in a multicenter randomized study, with between-group change favoring rifaximin at trend level versus no treatment. The randomized trial of rifaximin in covert hepatic encephalopathy used an open-label design. Cognitive performance was measured with the Stroop test, the study's primary endpoint. Within the rifaximin group, improvement on this measure reached p = 0.006 over follow-up. Cirrhosis-related adverse events were also less frequent with rifaximin over the same period.

This multicenter, open-label randomized controlled trial enrolled patients with covert hepatic encephalopathy associated with liver cirrhosis. Participants were assigned 1:1 to rifaximin or no treatment, and 50 patients completed the planned 12 weeks of follow-up after randomization. The primary endpoint was change in Stroop test performance. Secondary endpoints included NCT-B scores, serum ammonia levels, cirrhosis-related adverse events, and gut microbiota composition. These endpoints spanned cognitive, biochemical, clinical, and microbiome outcomes.

Stroop performance improved significantly in the rifaximin group, whereas controls showed no significant change over the same follow-up interval, with p values of 0.006 and 0.400, respectively. The between-group change favored rifaximin, at -4.45 ± 7.12 seconds versus -0.98 ± 5.74 seconds. The comparison did not meet conventional significance and was described as a trend. Among patients not receiving synthetic disaccharides at baseline, the change was -3.73 ± 5.96 seconds with rifaximin and -0.80 ± 5.86 seconds in controls, with p = 0.049. The authors interpreted these findings as suggesting that the Stroop test may be a sensitive endpoint for detecting treatment response in this population.

NCT-B scores and serum ammonia levels did not change significantly, with no parallel signal on those secondary cognitive and biochemical measures. Cirrhosis-related adverse events were significantly less frequent with rifaximin, with p = 0.006 for the group difference. Overall gut microbial diversity did not differ between groups, although rifaximin was associated with selective taxonomic shifts. The reported shifts included loss of the [Eubacterium] brachy group, while broader diversity measures remained similar between study arms. Rifaximin was associated with improved Stroop-measured cognitive performance and fewer cirrhosis-related adverse events during follow-up in these patients.