FYI...Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy.

[Guest guest]

http://www.clinicaloptions.com/Hepatitis/Journal%20Options/Collections/2010%20JO\

%20Hepatitis%20Volume%204/Articles/Bajaj_Gastroenterol_2010/Commentary.aspx

Rifaximin improves driving simulator performance in a randomized trial of

patients with minimal hepatic encephalopathy.

Bajaj JS, Heuman DM, Wade JB, et al.

Gastroenterology. 2011;140:478-487.

Expert Commentary Capsule Summary

Rifaximin Reverses Driving Difficulties in Patients With Minimal Hepatic

Encephalopathy

Mullen, MD

Posting Date: February 24, 2011

Professor of Medicine

Case Western Reserve University

Cleveland, Ohio

Several previous studies[1-5] have reported that minimal hepatic encephalopathy

(MHE) associated with cirrhosis results in driving difficulties among affected

patients (Capsule Summary).[5] Currently, there is no legal precedent to take

away driving privileges from patients who have MHE. However, it is important to

consider that individuals with MHE who drive may pose a risk not only to

themselves but also to fellow drivers on the road. As topical as this area of

research is, no one had heretofore demonstrated whether driving difficulties

associated with MHE are reversible.

Bajaj and colleagues[6] undertook this task in the current study (Capsule

Summary). The investigators randomized 42 patients with cirrhosis and MHE to

receive either rifaximin or placebo for 8 weeks in a double-blinded fashion.

Driving performance was assessed with a driving simulator at baseline and at the

end of 8 weeks of therapy. Importantly, the investigators found that driving

could be improved with rifaximin treatment. Indeed, the investigators reported a

significantly greater decrease in total driving errors between the rifaximin and

placebo arms (decrease in errors of 76% vs 33%; P = .013). This decrease

consisted of significant reductions in the number of speeding tickets (81% vs

33%; P = .005) and illegal turns (62% vs 19%; P = .012) for patients treated

with rifaximin vs placebo. Reductions in collisions, another component of total

driving errors, did not significantly differ between the rifaximin and placebo

arms at Week 8 (43% vs 33%; P = .751).

Another interesting finding of the Bajaj and colleagues study was that patient

quality of life showed little improvement with rifaximin. According to scores on

the Sickness Impact Profile (SIP) conducted at baseline and Week 8, only scores

on the psychosocial dimension improved significantly within the rifaximin arm (P

= .04); the total score and scores on the physical dimension and individual

dimensions of work, sleep and rest, eating, home management, and recreation and

pastimes remained unchanged. These findings contrast with those of a study by

Prasad and colleagues,[7] which reported significant improvements in the mean

total SIP score among patients treated with lactulose vs placebo for 3 months.

However, as discussed in the present paper, the difference in quality-of-life

outcomes may be due to the fact that patients were treated for longer in the

Prasad and colleagues study (3 vs 2 months), along with the fact that the Prasad

study was not double-blinded like the Bajaj study.

The study by Bajaj and colleagues establishes that patients who are diagnosed

with MHE based on a battery of psychometric tests do appear to have driving

problems. Although hepatologists are not well equipped to measure patients’

driving ability, they are in a position to establish whether MHE is present and

address the potential for driving difficulties. Importantly, driving problems

are reversible with HE therapy, suggesting that they are part of the spectrum of

hepatic encephalopathy.

Minimal hepatic encephalopathy is a very subtle condition associated with slight

changes in cognitive dysfunction that are typically detectable only with

specialized cognitive tests. Otherwise, the condition is almost undetectable by

normal clinical means. Although it is important to detect MHE since it predicts

later development of overt hepatic encephalopathy, there has never been any

strong indication to treat MHE patients with this minimal degree of cognitive

disorder. Accordingly, there are no guidelines recommending treatment for this

group of patients. The findings by Bajaj and colleagues may alter the treatment

landscape by prompting routine screening for and treatment of MHE. By drawing

attention to the possibility of driving problems among patients with MHE,

clinicians may be more inclined to automatically treat MHE even if driving

problems have not been rigorously established since it is now known that these

difficulties can be reversed safely and effectively.

References

1. Bajaj JS, Hafeezullah M, Hoffmann RG, et al. Navigation skill impairment:

another dimension of the driving difficulties in minimal hepatic encephalopathy.

Hepatology. 2008;47:596-604.

2. Kircheis G, Knoche A, Hilger N, et al. Hepatic encephalopathy and fitness to

drive. Gastroenterology. 2009;137:1706-1715.

3. Schomerus H, Hamster W, Blunck H, Reinhard U, Mayer K, Dölle W. Latent

portasystemic encephalopathy. I. Nature of cerebral functional defects and their

effect on fitness to drive. Dig Dis Sci. 1981;26:622-630.

4. Watanabe A, Tuchida T, Yata Y, Kuwabara Y. Evaluation of neuropsychological

function in patients with liver cirrhosis with special reference to their

driving ability. Metab Brain Dis. 1995;10:239-248.

5. Bajaj JS, Hafeezullah M, Zadvornova Y, et al. The effect of fatigue on

driving skills in patients with hepatic encephalopathy. Am J Gastroenterol.

2009;104:898-905.

6. Bajaj JS, Heuman DM, Wade JB, et al. Rifaximin improves driving simulator

performance in a randomized trial of patients with minimal hepatic

encephalopathy. Gastroenterology. 2011;140:478-487.

7. Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose

improves cognitive functions and health-related quality of life in patients with

cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007;45:549-559.

Link to the original abstract:

http://www.ncbi.nlm.nih.gov/pubmed/20849805?dopt=Abstract

[Guest guest]

http://www.clinicaloptions.com/Hepatitis/Journal%20Options/Collections/2010%20JO\

%20Hepatitis%20Volume%204/Articles/Bajaj_Gastroenterol_2010/Commentary.aspx

Rifaximin improves driving simulator performance in a randomized trial of

patients with minimal hepatic encephalopathy.

Bajaj JS, Heuman DM, Wade JB, et al.

Gastroenterology. 2011;140:478-487.

Expert Commentary Capsule Summary

Rifaximin Reverses Driving Difficulties in Patients With Minimal Hepatic

Encephalopathy

Mullen, MD

Posting Date: February 24, 2011

Professor of Medicine

Case Western Reserve University

Cleveland, Ohio

Several previous studies[1-5] have reported that minimal hepatic encephalopathy

(MHE) associated with cirrhosis results in driving difficulties among affected

patients (Capsule Summary).[5] Currently, there is no legal precedent to take

away driving privileges from patients who have MHE. However, it is important to

consider that individuals with MHE who drive may pose a risk not only to

themselves but also to fellow drivers on the road. As topical as this area of

research is, no one had heretofore demonstrated whether driving difficulties

associated with MHE are reversible.

Bajaj and colleagues[6] undertook this task in the current study (Capsule

Summary). The investigators randomized 42 patients with cirrhosis and MHE to

receive either rifaximin or placebo for 8 weeks in a double-blinded fashion.

Driving performance was assessed with a driving simulator at baseline and at the

end of 8 weeks of therapy. Importantly, the investigators found that driving

could be improved with rifaximin treatment. Indeed, the investigators reported a

significantly greater decrease in total driving errors between the rifaximin and

placebo arms (decrease in errors of 76% vs 33%; P = .013). This decrease

consisted of significant reductions in the number of speeding tickets (81% vs

33%; P = .005) and illegal turns (62% vs 19%; P = .012) for patients treated

with rifaximin vs placebo. Reductions in collisions, another component of total

driving errors, did not significantly differ between the rifaximin and placebo

arms at Week 8 (43% vs 33%; P = .751).

Another interesting finding of the Bajaj and colleagues study was that patient

quality of life showed little improvement with rifaximin. According to scores on

the Sickness Impact Profile (SIP) conducted at baseline and Week 8, only scores

on the psychosocial dimension improved significantly within the rifaximin arm (P

= .04); the total score and scores on the physical dimension and individual

dimensions of work, sleep and rest, eating, home management, and recreation and

pastimes remained unchanged. These findings contrast with those of a study by

Prasad and colleagues,[7] which reported significant improvements in the mean

total SIP score among patients treated with lactulose vs placebo for 3 months.

However, as discussed in the present paper, the difference in quality-of-life

outcomes may be due to the fact that patients were treated for longer in the

Prasad and colleagues study (3 vs 2 months), along with the fact that the Prasad

study was not double-blinded like the Bajaj study.

The study by Bajaj and colleagues establishes that patients who are diagnosed

with MHE based on a battery of psychometric tests do appear to have driving

problems. Although hepatologists are not well equipped to measure patients’

driving ability, they are in a position to establish whether MHE is present and

address the potential for driving difficulties. Importantly, driving problems

are reversible with HE therapy, suggesting that they are part of the spectrum of

hepatic encephalopathy.

Minimal hepatic encephalopathy is a very subtle condition associated with slight

changes in cognitive dysfunction that are typically detectable only with

specialized cognitive tests. Otherwise, the condition is almost undetectable by

normal clinical means. Although it is important to detect MHE since it predicts

later development of overt hepatic encephalopathy, there has never been any

strong indication to treat MHE patients with this minimal degree of cognitive

disorder. Accordingly, there are no guidelines recommending treatment for this

group of patients. The findings by Bajaj and colleagues may alter the treatment

landscape by prompting routine screening for and treatment of MHE. By drawing

attention to the possibility of driving problems among patients with MHE,

clinicians may be more inclined to automatically treat MHE even if driving

problems have not been rigorously established since it is now known that these

difficulties can be reversed safely and effectively.

References

1. Bajaj JS, Hafeezullah M, Hoffmann RG, et al. Navigation skill impairment:

another dimension of the driving difficulties in minimal hepatic encephalopathy.

Hepatology. 2008;47:596-604.

2. Kircheis G, Knoche A, Hilger N, et al. Hepatic encephalopathy and fitness to

drive. Gastroenterology. 2009;137:1706-1715.

3. Schomerus H, Hamster W, Blunck H, Reinhard U, Mayer K, Dölle W. Latent

portasystemic encephalopathy. I. Nature of cerebral functional defects and their

effect on fitness to drive. Dig Dis Sci. 1981;26:622-630.

4. Watanabe A, Tuchida T, Yata Y, Kuwabara Y. Evaluation of neuropsychological

function in patients with liver cirrhosis with special reference to their

driving ability. Metab Brain Dis. 1995;10:239-248.

5. Bajaj JS, Hafeezullah M, Zadvornova Y, et al. The effect of fatigue on

driving skills in patients with hepatic encephalopathy. Am J Gastroenterol.

2009;104:898-905.

6. Bajaj JS, Heuman DM, Wade JB, et al. Rifaximin improves driving simulator

performance in a randomized trial of patients with minimal hepatic

encephalopathy. Gastroenterology. 2011;140:478-487.

7. Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R. Lactulose

improves cognitive functions and health-related quality of life in patients with

cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007;45:549-559.

Link to the original abstract:

http://www.ncbi.nlm.nih.gov/pubmed/20849805?dopt=Abstract