Prevention of Recurrence in Hepatic Encephalopathy

Arun B. Jesudian, MD: Elliot, I know you’ve done some work on protocolizing inpatient care of patients with cirrhosis. And how do you and your team [at the] Michigan [Medicine Hepatology Clinic] take care of hepatic encephalopathy patients, and what recommendations might you have for providers out there who are not in a transplant center who don’t have hepatologists [or] specialized care?

Elliot B. Tapper, MD: Yeah, I think the key thing is that if you’re coming to a well-oiled machine, like Northwestern [Memorial] Hospital, when you come in you’re going to get that 4-pronged approach to care, and the patients are more often than not likely to be very well served. And the typical experience that we see is that someone presenting with pure hepatic encephalopathy ought to wake up very quickly. So...a few years ago, I noticed that some nurses were independently requesting additional doses of lactulose in the throes of overt encephalopathy, and their patients were waking up and going home earlier.

Anecdotally, but what we decided to do was to protocolize the care of hepatic encephalopathy. And what that does is it helps you in a context [in which] you might not have a hepatologist on staff, or the house staff [members] are rotating in and out and often like these templated notes about what to do for a given situation. So we gave a lot of lactulose up front, and we started rifaximin early not because we would expect it to [affect] in-hospital changes. But we [did] for 2 reasons. One is that oftentimes there’s the work of prior approval that must be done prior to the patient’s discharge. And two, the episode of care for hepatic overt hepatic encephalopathy does not end at the time of discharge. Because these patients have a risk of readmission that can exceed 30% [or] 40%. And you have to do everything you can to take the data that Dr. Flamm and his colleagues gave us to reduce that risk of another episode. And starting that therapy in hospitals is one of the best ways to make sure it gets done as an outpatient.

Arun B. Jesudian, MD: Steve, how effective [are] lactulose and rifaximin at preventing those episodes, preventing rehospitalizations?

Steven L. Flamm, MD: Another great question, Arun. You know this study, this pivotal study that was published in the New England Journal of Medicine in March 2010, was a very well-done study, which is why it was published in the New England Journal of Medicine. And the first, the primary outcome, metric, was recurrence of hepatic encephalopathy in these high-risk patients. Again, just to remind the audience, lactulose and rifaximin versus lactulose and placebo, 90% of the patients. The other 10% or so were rifaximin versus placebo because they weren’t on lactulose.

And in this 6-month period, the reduction in recurrence of encephalopathy in the rifaximin group, compared [with] placebo, was 58%, and it was highly statistically significant. This is a pretty remarkable reduction in a relatively short amount of time for a very bad thing, keeping in mind that rifaximin really again had no difference [adverse]-effect-wise compared [with] placebo. So that was the primary outcome measure.

Now the secondary outcome measure, there were many, but the most important one I would submit was hospitalizations related to encephalopathy—not just having encephalopathy, which was the primary outcome. And the reduction in hospitalizations [for] encephalopathy was 50%. Again, highly statistically significant. Again, a remarkable outcome with rifaximin for prophylaxis in a high-risk group. And consequently, this was adopted by the guidelines, which I mentioned earlier were published in late 2014 and really [are] now the standard of care around the world. In patients that have had encephalopathy, they should be maintained on rifaximin, usually with lactulose, because the study had most of the patients treated that way, for prevention of recurrence. Is it perfect? No. There were patients [who] still had recurrence and still were hospitalized. But there was a marked reduction, and that should be the standard.

And I do want to mention one last thing. That’s not happening a lot—I shouldn’t say a lot. It’s not happening enough around the nation in the United States. There are data to suggest that patients who should be on rifaximin for prophylaxis are not, for one reason or another. And we in the health care field who take care of these patients—hospitalists, primary care doctors, gastroenterologists—must, to optimize care for our care for our patients, treat these types of patients the way they should with a standard of care, and that would include rifaximin. Any thoughts, Elliot?

Elliot B. Tapper, MD: Yeah. I second that entirely. You know, after that pivotal randomized trial, there have been 2 observational studies. One from my center as a result of our protocol, and another from England, which was a multicenter study of before and after [that] used the rifaximin. And in both of those studies, you see an adjusted 40% reduced reduction in the rate of readmission.

You know, readmissions are one of the worst things that can happen to a patient and to a hospital. But cirrhosis is almost unique in a way in that there’s a pill to reduce the risk of readmission. And that doesn’t mean everybody should be on rifaximin, right? But it means that people who are at risk for readmission should be on the optimal therapy for hepatic encephalopathy, which in my opinion includes teaching and adequate dosing of their lactulose and cotherapy with rifaximin.

David M. Salerno, PharmD: One other point I would add is something we’ve been doing in New York, trying to increase the amount of medicines that make it to the patient’s bedside before discharge. Because as you alluded to before, Elliot, talking about the transitions of care to prevent these patients from coming back to the hospital is so important. So if we could give the patient not only the education but all the tools and the things that they’re going to need to be at home in order to prevent readmission, such as bringing the medicines to the bedside, showing the caregivers how to use [them], giving them a medication list, getting [all of those prior authorizations and] making sure [those] things are taken care of before the patient leaves the hospital is one of the important points of making sure that rifaximin is going to be able to do its job.

Arun B. Jesudian, MD: Absolutely. So secondary prophylaxis of these episodes is of paramount importance. So being on the right therapy and making sure the patient actually has the medication and knows how to take it properly.

Transcript edited for clarity.