The Advancement of Minimal Hepatic Encephalopathy Diagnosis

Arun B. Jesudian, MD: Great. Just to summarize, overt HE [hepatic encephalopathy] encompasses stage II, III, and IV. And then covert hepatic encephalopathy is the stage I and also something called minimal hepatic encephalopathy. So, Elliot, what is minimal hepatic encephalopathy, and how might you pick that up?

Elliot B. Tapper, MD: Yeah. So I think minimal [hepatic] encephalopathy is the idea that if you provoke a patient through some fancy standardized formal neuropsychiatric test or if you put an EEG [electroencephalogram] machine on them, you might see some changes in brain wave pattern that are manifested predominantly in deficits of executive function. They’re not going to be great at math, essentially. And you can put them through a battery of tests to define that, but that’s predominantly the domain of research, and there [are] a lot of pitfalls in that diagnosis.

But taking a step back, focusing a little bit more on the symptoms or like asking a patient how they’re feeling, I want to bring up a few points. One is that if you’re asking a patient about falls, sleep, [or] irritability, you might be able to identify somebody with these early stages of encephalopathy, or these symptoms are in fact nonspecific. But depending on your index of suspicion that it’s a change in that person, you may be likely to attribute it to hepatic encephalopathy.

So, broadly, HE causes 2 different types of changes in patient-reported outcomes: 1) to the patient and 2) to the caregiver. And it’s important not to forget that that other person in the room with them, their life is being turned upside down by the revolving door of hospitalizations that is often caused by hepatic encephalopathy. There are standard forms that one can do to demonstrate the presence of caregiver distress, but I think in practice it’s important just to say, “Hey, how are you doing” and focus a little bit on perhaps referring the caregiver for their own support. But in general, patients with [hepatic] encephalopathy will experience deficits in their practice, in their work, [and] they’re more likely to present with depression and disability.

Arun B. Jesudian, MD: Thank you. I think that’s such an important point about the caregiver, because this is a condition that is burdensome, not just to the patient who’s affected [but] to the person who has to care for them, to the health care system because they’re so frequently admitted. And that’s why it’s important for us to understand it and know how to treat it effectively. Before we transition into treatment, just a question about…apps that are available that could maybe detect some of this early stage minimal and stage I HE. Are either of you utilizing them? Do you find them to be helpful [and] practical in your practice?

Elliot B. Tapper, MD: Yeah. So what you’re getting at is there are these tools that have been validated in experimental populations of very clean cohorts of well-defined patients with cirrhosis. They’re not drinking alcohol; they’re not on medications that could be sedating. But in general, your performance on some of these apps…[is measured by] the time it takes for you to correctly complete some games. The best one out there is called the EncephalApp Stroop [test]. Essentially, this is a test that goes back many decades, taken from the literature on ADHD [attention-deficit/hyperactivity disorder], actually. I suggest that you download it and do it yourself before you ask a patient to do it.

But we’re doing it in research, and if you’re interested in tracking someone’s cognition, and you’ve got a completely with-it patient or someone who’s got a highly technologically savvy caregiver, it’s not an unreasonable test. I wouldn’t use the cutoffs that are published in the literature to define who has minimal [hepatic] encephalopathy, but within a given person, you can see variance. And if someone is doing much worse than they were at baseline, that could be a sign that they’re getting behind on their treatment, that you may need to change something about their medical care. That’s my particular takeaway from the literature on these tools.

Steven L. Flamm, MD: I agree. Minimal HE right now, I think, is very important. These patient-reported outcomes have been underemphasized in the past. Fortunately, with important researchers like Elliot…making these issues much more clinically relevant, which they are, and giving us data—plus, from a regulatory standpoint, patient-reported outcomes are becoming increasingly important now for approval of medications for many different disease states—this is going to be more important. And I believe in the future, minimal HE will become much more prominent in our care of patients with cirrhosis. And we will use things like these apps for diagnosis because they’re easy and they have been validated.

In the past, we’ve used pencil-and-paper tests, and there are some other computer-based [tests] that have been used, but they’re a little more, I’d say, difficult to administer and grade than some of these apps. So I think we will be using them more. More research will evolve, and when we have definitive therapies for patients with minimal HE to follow, it will become even more important.

David M. Salerno, PharmD: I tend to find that I like the use of apps as a way or a mechanism to try [to] engage patients in their care. And the same goes for their caregiver [who’s] there with them. So more often than not, when I’m counseling a patient, I’m trying to find a way in which they’re going to participate in their care. And I feel that utilization of these apps is one way that you can engage a patient who’s not so participatory in their care, and you can also use it as a mechanism for those patients who really like to take control of their own care.

Arun B. Jesudian, MD: Definitely.

Elliot B. Tapper, MD: If I could add just one thing. Again, minimal [hepatic] encephalopathy [is] largely the domain of research but very important. And if you’re so inclined to treat it, and you think that something is going on with your patient that’s potentially reversible but [are] looking for some concrete evidence, a number that you can track, that app is useful. And if I could put a plug for 1 other test like this, it’s kind of fun. It’s called the animal-naming test. And it takes a minute to do, and you simply ask the patient, and you count how many unique animals they can name. And if they can rattle off dozens of animals, [it’s likely] that they do not have minimal [hepatic] encephalopathy, but you can track the number of animals that your patient is willing to disclose.

Arun B. Jesudian, MD: Yeah, that’s a great one and very easy to do. Doesn’t require any technology, [and it’s] only 60 seconds.

Transcript edited for clarity.