Clinical Trial Data for Rifaximin in Treatment of HE

Arun B. Jesudian, MD: Forrifaximin, the FDA-approved indication is preventing recurrent episodes of overt hepatic encephalopathy [HE]. For the audience, a pivotal trial in 2010 New England Journal of Medicine demonstrated that, by and large, patients who took both lactulose and rifaximin had substantial risk reduction in a breakthrough episode of overt hepatic encephalopathy and an HE-related hospitalization over 6 months. Do you find that to be true in your clinical practice? It’s been awhile since that study, and studies have continued to show that patients on dual therapy are less likely to have breakthrough episodes and be in the hospital. Is that your experience as well?

Kimberly A. Brown, MD: Absolutely. Rifaximin was 1 of the best tools that came about in my career for liver disease. It’s interesting to go back to that trial and think through why the FDA recommended what it did. It was because of how the trial was designed. The trial was designed where you had to have 2 episodes before you had it. If you think that through, that’s why. It’s to prevent recurrence after the initial episode. The way I’ve used it clinically is to move it forward. I don’t wait. I don’t place a patient on lactulose and then wait for another episode to occur. I’m often moving rifaximin forward, which wasn’t how the trial was designed, but it makes sense to me. Why would I wait for another episode when we know that the majority of patients on lactulose will have another episode? I move it forward and often discharge patients on both.

Arun B. Jesudian, MD: We do the same mainly because those recurrent episodes, especially if they lead to rehospitalization, are costly in terms of patient outcomes. The mortality is high for patients with decompensated cirrhosis who end up in the hospital. It can be 25% or so. Those who’ve been admitted with HE and are back within a month have much worse outcomes than those who can stay out of the hospital.

Kimberly A. Brown, MD: You’re right. To your point, the risk of death is much higher in patients who have readmission. The other thing that we don’t talk about much, because we don’t have a lot of data, is the long-term effect on the brain in patients who have recurrent episodes. It’s a little scary because this is a completely reversible phenomenon with transplant. But we’ve seen some data with MRI that changes of the brain seem to be permanent. Some testing in the post-transplant setting show that deficits remain. I worry that allowing a patient to have these severe recurrent episodes is not the best plan.

Arun B. Jesudian, MD: I agree.Beyond the hospitalization and the risk of mortality, the cumulative effect on their brain could be long-lasting cognitive decline—even if they get to a transplant, which is our hope for all patients in this situation.

Transcript edited for clarity