Importance of Early Recognition and Treatment of Hepatic Encephalopathy - Episode 8

Use of Lactulose and Rifaximin in HE Treatment

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Kimberly A. Brown, MD, reviews the use of lactulose and rifaximin as first-line treatment of hepatic encephalopathy.

Arun B. Jesudian, MD: In terms of treatment for hepatic encephalopathy, give us a sense of the first- and second-line therapies, lactulose and rifaximin. How do they work, and how do you use them clinically in your outpatients?

Kimberly A. Brown, MD: When you look at our guidelines, historically, we’ve gone to lactulose as a first-line therapy. How it works is a mystery to most of us. We know it increases bowel movements. That’s 1 of the best effects. If I can teach my primary care colleagues anything, it’s that you have to keep patients stooling. Once they become constipated, they become encephalopathic. But we also know that lactulose changes the pH in the gut and probably has effects in that way as well.

We don’t use lactulose appropriately. There was a study years ago to suggest that as high as 60% of patients who are prescribed lactulose don’t take it. It’s not particularly appealing to patients. It causes a lot of gas, and it’s sweet and syrupy. Even though we might be prescribing it, they might not be taking it. I prescribe lactulose as a first-line agent to try to increase bowel movements, and I recommend 3 to 4 a day. I also spend a lot of time telling patients that this is 1 of the medications they adjust themselves and how to adjust it. They don’t wait for me to adjust it. They adjust it at home because it’s important that they’re achieving 3 to 4 bowel movements a day.

Rifaximin has been a great tool. It’s 1 of the game changers for hepatology because of how it works, how easy it is to take for patients, and how effective it is. I add it to lactulose very quickly in my patient population because, as we know, the primary benefit of rifaximin is to prevent recurrence. That’s what it does. We see that in clinical practice. Patients have longer periods before they get another episode, and hopefully they don’t have another episode that lands them in the hospital.

Arun B. Jesudian, MD: I agree completely. I commonly use the 2 together, especially if a patient has declared themselves as having a major episode that required hospitalization. They’ve put themselves in that category where their risk of having a recurrent episode or a recurrent hospitalization is so high that it’s helpful to be on both lactulose and rifaximin. Lactulose is a bit difficult to prescribe because it’s less about what we write on the prescription and more about what it takes for that individual patient to have the goal number of bowel movements. Sometimes we’ll say 2 to 3 or 3 to 4, depending on the patient. It’s tough because they have to titrate it themselves, and if the disorder impairs them, that can affect their ability to take the appropriate amount of lactulose.

But it works when taken appropriately, probably because of those effects that you mentioned: decreasing the bacterial burden through bowel movements so there is less ammonia generation, and shifting that pH balance so that form of ammonia isn’t crossing the blood-brain barrier. Or so we think. It’s clearly beneficial beyond the laxative effect, which is why we continue to use lactulose despite the fact that patients hate the taste, the bloating, and everything that goes along with it.

Kimberly A. Brown, MD: I’m at a large center, as you are. Many patients who come in have never been treated for liver disease. If encephalopathy is their presenting event, I’ve started lactulose and rifaximin at the same time and then tried to continue them as an outpatient. But if I have an outpatient who starts with those subtle signs, if they can tolerate lactulose, I try that. Sometimes they can’t, and I’ll try rifaximin alone in those patients. Some of our patients have baseline diarrhea, and they’re not going to take lactose. I will go to rifaximin immediately for those patients.

Arun B. Jesudian, MD: I do the same. If someone is intolerant of lactulose for 1 reason or another—and oftentimes, the number of bowel movements they’re already having is that reason—then I’ll use rifaximin by itself. In my experience, that can work in that situation. I’d love for patients to be on both, but they can be on the monotherapy rifaximin if needed. In patients who you might suspect have covert or minimal hepatic encephalopathy, do you have a treatment preference?

Kimberly A. Brown, MD: In those patients, I often don’t know what it is. You get very subtle signs. I’ve given them a trial of rifaximin to see if that can sort it out clinically. Do they feel better? Are they are able to think more clearly? If the answer is yes, then I keep them on it. The reason I’d go to that first is that it’s not an emergency. They’re not in the hospital or encephalopathic, so I don’t need to wake them up quickly. But I worry that if I try lactulose in patients with very subtle symptoms, they won’t get a good trial because they’ll be taking this medication they don’t like and they’re not sure why they’re taking it.

Arun Jesudian, MD: I’ve done the same because this might be an accountant who feels a little brain fogginess, and it doesn’t seem right to have them running to the bathroom 3 times a day to see if we can improve that. Rifaximin in that situation is something I’ve tried.

Transcript edited for clarity