Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy.
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.
Bajaj
Jasmohan S
JS
Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia 23249, USA. jsbajaj@vcu.edu
Heuman
Douglas M
DM
Wade
James B
JB
Gibson
Douglas P
DP
Saeian
Kia
K
Wegelin
Jacob A
JA
Hafeezullah
Muhammad
M
Bell
Debulon E
DE
Sterling
Richard K
RK
Stravitz
R Todd
RT
Fuchs
Michael
M
Luketic
Velimir
V
Sanyal
Arun J
AJ
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
D000890:Anti-Infective Agents; D016207:Cytokines; D012294:Rifamycins; D000641:Ammonia; D000078262:Rifaximin