title: Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia 23249, USA. jsbajaj@vcu.edu
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heuman
authors.forename: James B
authors.initials: JB
authors.lastname: Wade
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Gibson
authors.forename: Kia
authors.initials: K
authors.lastname: Saeian
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Wegelin
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hafeezullah
authors.forename: Debulon E
authors.initials: DE
authors.lastname: Bell
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: R Todd
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Michael
authors.initials: M
authors.lastname: Fuchs
authors.forename: Velimir
authors.initials: V
authors.lastname: Luketic
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
mesh_terms: D000641:Ammonia / Q000097:blood; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001334:Automobile Driving; D003071:Cognition / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008875:Middle Aged; D010349:Patient Compliance; D011788:Quality of Life; D012294:Rifamycins / Q000009:adverse effects / Q000627:therapeutic use*; D000078262:Rifaximin; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D012294:Rifamycins; D000641:Ammonia; D000078262:Rifaximin