Arun Jesudian, MD

Any other things that you counsel your patients about? Certainly, medications can exacerbate hepatic encephalopathy. Do you go through their list in detail, and do you call out certain classes of medicines?

I do, particularly those patients who are taking any kind of narcotics. Oftentimes we struggle because those patients have often been on narcotics for a long period of time. Trying to work with their providers to see if there are alternatives and trying to help them understand that more narcotics are just not good. A dose of narcotics they may have been fine with 8 months ago may be too much for them now in terms of precipitating encephalopathy.

We try to avoid sleeping pills. I know it’s hard. You know, we tend to use the shortest-acting ones if we can—but recognizing that patients with liver disease don’t metabolize things well so they may have untoward effects from that. I think even with antidepressants, oftentimes doses might need to be adjusted in patients with advanced liver disease. Those are the biggest things.

I try to have them avoid supplements if they don’t know what’s in them because even though it’s over the counter, somehow patients think it’s safe. Oftentimes, it may not be safe, depending on what it is. I try to supplement vitamins in all of my patients, just a general multivitamin. And then, as you know, in patients who have more cholestatic liver disease or high bilirubin, they can become deficient in fat-soluble vitamins. I personally think that vitamin D is important. I know we’re not supposed to check it in all patients routinely, but I do check it in my patients with advanced liver disease. I think there’s lots of evidence that vitamin D, at least normal levels, are beneficial in patients for a variety of reasons. Those are the biggest things that I do.

People will often ask and probably ask you as well: What about milk thistle? Can I take it? What I tell them is that the studies that showed any benefit gave it in intravenous form for completely different reasons. So whether it works for their condition in oral form, I don’t really have an opinion, but I don’t think it’s harmful. Other things I think could potentially be harmful, but I think milk thistle is not harmful; but I’m not convinced it’s helpful.

That’s virtually identical to how I counsel my patients about milk thistle. But the other supplements for sure I try and dissuade them from, especially if it’s some sort of herbal supplement or multiple ingredients, because the last thing we want is some sort of liver toxicity on top of their end-stage liver disease. That would really be a bad combination.

Thank you to Dr Brown for this rich and informative discussion, and thank you to our viewing audience. We hope you found this 

® discussion to be useful and informative. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming programs and other great content right in your inbox.

Videos

Hepatology experts discuss educating patients with hepatic encephalopathy on managing medications and supplements.

Counseling Patients on Managing Medication in HE

Is there a way that you educate your patients about [hepatic encephalopathy]? I find this to be challenging. Even for you and me today, it’s tough to talk through the pathophysiology. We kind of wave our hands and say we don’t fully understand it. How do you explain the conditions to your patients and why they should be taking those medications?

I have 40 minutes with a new patient. I would say 30 minutes is spent with a diagram talking about cirrhosis and portal hypertension because everything they experience is related to portal hypertension, including encephalopathy—so helping them understand sort of why these things are happening and then helping them understand how we try to mitigate those effects with sodium restriction, water pills, rifaximin, or variceal banding. So just trying to help them understand why it’s happening and then for each of those conditions, how best to manage it.

Yes, I feel the same way, and unfortunately, I’m not always able to…draw out a diagram for them, but I think it is extremely helpful when they can see a pictorial representation of portal hypertension and why these problems are happening. And when it comes to the medications themselves, do you counsel them about anything in particular? Certainly, too much lactulose would cause diarrhea, which is problematic. Do you tell them anything else so that you might improve their likelihood of staying on the medications?

I think the biggest point to try to get across is that this is not an intermittent treatment; it’s a preventative treatment. Sometimes patients walk away with a medication, and they think they’re only supposed to take it if X, Y, and Z happens—but in fact, we’re trying to prevent X, Y, and Z. So, it’s mostly adherence. With lactulose trying to really not be constipated, try to have those bowel movements every day, to take extra doses if they do become constipated, and to hold it if they get sick. We don’t want them to have ongoing diarrhea if they’re ill and losing fluids because that by itself can precipitate an event. And for rifaximin, making sure that they take it twice a day, don’t miss doses, and keep taking it to try to prevent those episodes.

And when you come across the patient who’s clearly adherent but has persistent or refractory hepatic encephalopathy, what do you do at that point? Do you conduct any further diagnostic work-up? Do you add on third-line therapies? What’s your approach?

I don’t think I have a third-line therapy, but what I do is I look for large shunts. So I will often either go back to their original cross-sectional image or repeat a cross-sectional image to look. I have had a handful of patients in whom we’ve been able to occlude very large shunts in their groin or elsewhere in the abdomen that has helped. So that’s really the next step for me. Hopefully, these patients are listed for transplantation. Unfortunately, as you know, you can’t get an exception for encephalopathy.

It’s interesting, having sat on the [Liver and Intestinal Organ Transplant Committee] , we talked about MELD [Model for End-Stage Liver Disease] exceptions and how we’ve standardized those. And really, if you look back at the philosophy, we’ve altered the way we’ve allowed exceptions based on mortality risk for the patient. I think moving forward, we’re going to see that there is a mortality difference in patients with recurrent encephalopathy. Hopefully those data can support MELD exceptions, but currently they don’t.

Right. I agree completely with you. This is such a stressful type of patient to manage. When you have that patient whom you know has brittle encephalopathy, they make you very nervous about their clinical course, particularly if their MELD score is low and if their access to transplant is low.

I also agree with imaging for spontaneous shunts as a cause of refractory encephalopathy. We found that although we’re getting MRIs usually every 6 months for HCC [hepatocellular carcinoma] screening, the radiologist is not always looking for shunts. We often have to look ourselves or ask them to revisit the images and see [whether] they can see a splenorenal shunt, for example, that we might embolize in a situation where the encephalopathy is really refractory and where we can tolerate some worsening of the portal hypertension.

Have you ever used BRTO [balloon‐occluded retrograde transvenous obliteration]?

I guess we have, but usually when there’s a combination of a bleeding problem and we find large shunts where the patient can benefit. I have not, that I can recall, used it exclusively for encephalopathy. Have you?

I thought about it in one patient. Unfortunately, that individual had an untoward event, so it was difficult to understand whether it would have been effective. But it does actually increase portal flow to the liver, so you might think it might lessen shunting. It’s just something that I’ve thought about in the past for these patients who have bad recurrent encephalopathy.

I think certainly as interventional radiologists become more comfortable with these advanced procedures, we’ll probably be utilizing them more and more than we have been traditionally. Especially if you can improve the usual flow through the liver. It has to benefit the patient in a number of ways that we might not see until after the fact.

Thinking holistically about these patients, nutrition is certainly important. Do you counsel them about nutrition? If so, what do you tell them, or…do you have a dietician or a nutritionist who’s involved?

Yeah, great points. We do have a dietician that sees all of our patients with liver disease. But one of the things that I’ve been saying for years—again, you and I were both at a meeting recently, and Jennifer Lai, MD, said out loud—eat 6 meals a day and especially the meal at night right before bed. What I do tell patients, all of my patients, is we all need glucose for our hearts and our brains. If we are not taking nutrition, our livers make it for us. And the building blocks for that are our muscle stores, those amino acids.

If it takes you and me a long period of time to move into a fasting state, it sometimes takes patients with advanced liver disease just a few hours. And so it’s critical, in my opinion, that they eat small meals throughout the day, and the most important one is that one at bedtime. In fact, we just saw some information that nighttime feedings were actually more beneficial than daytime feedings for patients with advanced liver disease. Now I don’t know exactly why that is, why night would be better than day, but I think the important point here is your longest period of fasting is going to be between bed and breakfast. So I do counsel all of my patients on that.

Certainly, sodium restriction is important. I try to help them understand how much salt they’re eating. The story that I tell is that if you’re a normal American, you’re eating about 7000 mg of salt a day. If you simply take away the saltshaker, it’s about 4000 mg. I’m asking them to get to 2000 mg, and they think that’s a big number. In some patients, in the absence of water pills, I can only get them to urinate about 600 mg out a day. So, I say do the math: You’re taking in 2000 mg, you’re peeing out 600 mg, so that means you’re going to retain salt and water every day. Water pills can only do so much. We talk about protein too. I try really hard to emphasize that protein should be taken in some form at every meal. People don’t know what protein is, so that’s where the dietitian is helpful.

Yes, I agree completely. These patients oftentimes find it difficult to eat large meals, they’re full of ascites, they’re taking lactulose, which doesn’t taste very good and bloats them, and they generally feel ill. And I think talking about what those small meals should consist of is important because usually they can only accommodate a small amount at a time. But if they’re doing that frequently and doing that before bedtime, you can offset at least some of this muscle breakdown, which is so deleterious in terms of encephalopathy, their overall trajectory, and—if they are going to become a transplant candidate—their ability to get through the surgery and recover in a timely manner after that major surgery.

Kimberly A. Brown, MD, shares approaches to educating patients on management of hepatic encephalopathy and the importance of medication adherence and nutrition.

Patient Education of HE

Jim, I want to close by discussing how patients are discharged, which is usually outside your purview. I don’t anticipate you discharge many of these patients, but I want to talk about the admission fully. If a patient who is admitted with HE [hepatic encephalopathy] is nearing discharge, some things that are important to keep in mind are how we can strategize for them to get appropriate, follow-up, treatment, and hopefully not end up back in the emergency department [ED] within a month or so. At my institution [Weill Cornell Medical College], we try and educate the patient about the disease. It’s not necessarily straightforward for them to understand why their brain is affected by cirrhosis and how that has a lot to do with bacteria in their intestines. The medications lactulose and rifaximin help prevent that, but we try to discuss the basics of the pathophysiology of hepatic encephalopathy, how ammonia plays a role in having adequate bowel movements, and how taking this antibiotic can help prevent them from ending up back in the hospital.

We prescribe them the medications they need. Rifaximin often requires prior authorization, so we want to make those prescriptions clear in terms, saying that the indication is overt hepatic encephalopathy and they were hospitalized with it. If they’re intolerant of lactulose or if they failed lactulose, it’s important to include the right ICD-10 [International Classification of Diseases, Tenth Revision] code. We try to start that process early so that they don’t run into a lapse in medications. That brings up a question for you. Do you see patients whose major reason for coming in is that they didn’t have access to medication?

 That’s a challenge for a lot of patients, particularly those living on their own. Perhaps they don’t have a strong support network. Maybe they did have a strong support network, but recurrent HE sometimes exhausts family members and leaves patients on their own. It’s a challenge if they can’t get support, don’t know how to get it, or won’t get it. The No. 1 thing we can do is provide good follow-up for these patients.

I imagine you have a great case manager network at your facility. We have it at our facility too, although I don’t discharge most of these patients. On the backside, when hospitalists discharge them, we have case managers calling these patients to make sure they’re getting their medication and to see how they’re doing. Those 2 open-ended questions—are you getting your medications? How are things going?—are helpful to minimize progression for relapse.

In the emergency department, the most important thing we can do to help with this continuity of understanding of HE and ongoing treatment is to diagnose HE. Rather than admitting the patient with a diagnosis of a generic altered mental status, which doesn’t help much, try to refine it: yes, they did have a GI [gastrointestinal] bleed plus or minus SBP [spontaneous bacterial peritonitis], but also mention hepatic encephalopathy explicitly because that will help them then get the medication as an inpatient but also as an outpatient.

Such important points. I completely agree with the case-management aspect. We can prevent a significant subset of admissions by someone just calling them and picking up on early encephalopathy that can be managed at home. For example, sometimes patients need to take a little extra lactulose. That could avoid an emergency department visit or an admission that can be costly in a number of ways: outcome, days in the hospital, dollars spent. Sometimes they need a sooner follow-up appointment than what’s been scheduled for them. If someone is checking in the first few days and they recognize that, that can potentially be a way of keeping them out of the hospital. Thank you for bringing that up and the importance of attaching that diagnosis to their hospitalization, even though they might have several diagnoses. These patients are medically complex, but in terms of access to medications, having that HE diagnosis—both in the hospitalization and potentially on the prescription—is important.

We learned this decades ago with congestive heart failure as it proliferated: when we have close follow-up with case management, we can minimize any recurrence of ED visits or hospitalizations and access to medications. That’s key. No. 1 you have to make the diagnosis, and No. 2, you have to take your medication to treat it.

Exactly. If we can do that reliably or achieve that on behalf of our patients, we’ll be taking much better care of them and preventing a lot of admissions, or at least the preventable ones.

 Thank you for this rich and informative discussion. Before we conclude, I’d like to get final thoughts from you. Dr Williams, is there anything you want to add?

It’s been a pleasure having this conversation with you and our colleagues. Thank you for the opportunity. My final thought is that in the emergency department, when you have complex patients with altered mental status, you have to at least consider hepatic encephalopathy, as not just the sole diagnosis but often a joint diagnosis. You have to treat both aggressively and start early just as you would any other patient in the emergency department. Remember, it’s not a unifying diagnosis of a singular diagnosis of sepsis. We typically have to treat sepsis and HE aggressively. Even if it’s subtle, if it’s not over. With HE, which is easy to diagnose, you want to start treatment early and don’t want to depend on your serum ammonia level. It’s a clinical diagnosis.

 I like that as a closing thought: don’t depend on your serum ammonia level. Thank you. To our viewing audience, we hope you found this 

 to be useful and informative. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming 

Drs Arun Jesudian and James William discuss approaches for proper discharge planning and transition of care and how this can reduce readmission for patients with hepatic encephalopathy.

Discharge Planning and Transition of Care in HE

I want to ask you to grade emergency medicine. What are some things that are missed sometimes? What would you tell all the emergency physicians to consider in these patients?

First and foremost, the approach that you suggested is an ideal 1 for emergency medicine physicians. I completely understand that there’s so much going on in your typical emergency department, with many types of patients coming through the door. By no means do I want someone to think exactly the way I do in terms of liver disease. Keeping hepatic encephalopathy [HE] on the differential diagnosis for any patient is important because this might be their first episode, and they might have undiagnosed cirrhosis. That’s important to be aware of as you’re assessing patients with altered mental status. Look for signs of chronic liver disease that might tip you off to that diagnosis.

Everything we’ve discussed are the important elements of an initial evaluation: ruling out other causes, not necessarily relying on a serum pneumonia level, and going through that checklist of potentially precipitating events. This is probably the most important part of this evaluation because you’ll find a lot of life-threatening diseases that way: serious infections, variceal or other gastrointestinal bleeding, hepatorenal syndrome, significant electrolyte disturbances, even liver cancer, hepatocellular carcinoma. Those can be picked up relatively quickly.

It’s important to initiate treatment early. If those things happened in patients with HE in the emergency department, we’d be in a much better situation nationwide in terms of outcomes, length of stay, and probably readmissions. It seems straightforward when you and I are talking, but it’s tougher in the real world. I can’t imagine how many patients you see during a shift and how many different diseases you encounter. Hopefully, we’re raising some awareness about hepatic encephalopathy, which is an increasingly encountered diagnosis in the hospital.

You’re right. When you talk about the increasing incidences, it’s going to be dramatic, particularly with nonalcoholic steatohepatitis. And obesity is such a challenge in our country; one-third of Americans are not just overweight but obese. This could potentially be a dramatically increasing concern.

It is. I’m sure you’ve encountered what we have, which is that over the past few years with the COVID-19 pandemic, we’ve also seen an increasing number of patients with alcohol-associated cirrhosis and alcoholic hepatitis, both of which can cause hepatic encephalopathy. We’re seeing more sick patients with end-stage-type liver disease. The 2 major drivers of that are fatty liver disease, and there’s quite a bit of alcohol-associated liver disease.

A transplant hepatologist shares advice for emergency department physicians and clinicians to improve the diagnosis and treatment of hepatic encephalopathy.

Arun Jesudian, MD

Articles