Rifaximin Improves Driving Simulator Performance in a Randomized Trial of Patients With Minimal Hepatic Encephalopathy

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 140; no. 2; pp. 478 - 487.e1
• Main Authors: Bajaj, Jasmohan S, Heuman, Douglas M, Wade, James B, Gibson, Douglas P, Saeian, Kia, Wegelin, Jacob A, Hafeezullah, Muhammad, Bell, Debulon E, Sterling, Richard K, Stravitz, R. Todd, Fuchs, Michael, Luketic, Velimir, Sanyal, Arun J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2011
• Subjects: Ammonia - blood; Anti-Infective Agents - adverse effects; Anti-Infective Agents - therapeutic use; Automobile Driving; Cirrhosis; Cognition - drug effects; Cognitive Function; Cytokines - blood; Driving Performance; Gastroenterology and Hepatology; Hepatic Encephalopathy - drug therapy; Hepatic Encephalopathy - psychology; Humans; IL-10; Middle Aged; Patient Compliance; Quality of Life; Rifamycins - adverse effects; Rifamycins - therapeutic use; Severity of Illness Index; Treatment Outcome; NSE; Cognitive Function; minimal hepatic encephalopathy; IL; neuron-specific enolase; DST; digit symbol test; block design test; sickness impact profile; inhibitory control test; NCT-A/B; MHE; IL-10; Cirrhosis; Driving Performance; BDT; ICT; number connection test A/B; SIP; interleukin
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2010.08.061

Background & Aims Patients with cirrhosis and minimal hepatic encephalopathy (MHE) have driving difficulties but the effects of therapy on driving performance is unclear. We evaluated whether performance on a driving simulator improves in patients with MHE after treatment with rifaximin. Methods Patients with MHE who were current drivers were randomly assigned to placebo or rifaximin groups and followed up for 8 weeks (n = 42). Patients underwent driving simulation (driving and navigation tasks) at the start (baseline) and end of the study. We evaluated patients' cognitive abilities, quality of life (using the Sickness Impact Profile), serum levels of ammonia, levels of inflammatory cytokines, and model for end-stage-liver disease scores. The primary outcome was the percentage of patients who improved in driving performance, calculated as follows: total driving errors = speeding + illegal turns + collisions. Results Over the 8-week study period, patients given rifaximin made significantly greater improvements than those given placebo in avoiding total driving errors (76% vs 31%; P = .013), speeding (81% vs 33%; P = .005), and illegal turns (62% vs 19%; P = .01). Of patients given rifaximin, 91% improved their cognitive performance, compared with 61% of patients given placebo ( P = .01); they also made improvements in the psychosocial dimension of the Sickness Impact Profile compared with the placebo group ( P = .04). Adherence to the assigned drug averaged 92%. Neither group had changes in ammonia levels or model for end-stage-liver disease scores, but patients in the rifaximin group had increased levels of the anti-inflammatory cytokine interleukin-10. Conclusions Patients with MHE significantly improve driving simulator performance after treatment with rifaximin, compared with placebo.