Advances in the Treatment of Overt Hepatic Encephalopathy: W

Transcript

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Welcome to CE on ReachMD. This activity is provided by TotalCME and is part of our MinuteCE curriculum.

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Dr. Reau:
This is CE on ReachMD, and I'm Dr. Nancy Reau. Here with me today is Dr. Arun Jesudian.

Arun, what's in the pipeline for treating overt hepatic encephalopathy?

Dr. Jesudian:
Yes, thanks for the question, Nancy. There are therapies being studied that might improve how we take care of these patients. So, for example, could we prevent the first episode of hepatic encephalopathy in patients with cirrhosis?

So we know that microbial dysbiosis in cirrhosis is associated with altered bile acids, and rifaximin is being studied in a newer preparation, the SSD—or soluble solid dispersion—preparation that was formulated specifically to increase water solubility in the GI tract of the rifaximin molecule, and also minimize systemic exposure, as is the case with the current version of rifaximin. And this is particularly important in patients with low bile flow, like our patients with advanced cirrhosis.

And so this preparation is being studied in patients with cirrhosis who have not yet had overt hepatic encephalopathy to see if we can prevent them from having that first episode of overt hepatic encephalopathy and potentially other complications of cirrhosis, because we know that microbial dysbiosis is so important in the pathophysiology of many complications of cirrhosis. So that's one exciting study that's ongoing, and we should be hearing those results soon.

Dr. Reau:
That is really exciting. Now, in our pool of patients that have cirrhosis, many of which have compensated or asymptomatic cirrhosis, some are going to be a little higher risk for decompensation with that first episode of HE, and I think that the RED-C trial pulled a little bit of that in.

So some of the criteria to be a participant in that study included signs of, I think, portal hypertension, right? So that you can take the messaging away from the RED-C trial enrollment and also look at the patient sitting in front of you.

Can you review a little bit of just the very general criteria to participate in RED-C?

Dr. Jesudian:
Yes. These were patients who not only had cirrhosis but they clearly had clinically significant portal hypertension in that they had to have medically controlled ascites. So they were patients who had demonstrated that their portal hypertension was severe enough to cause ascites, but they weren't a patient who was very decompensated. Those patients probably would be difficult to study for this indication, which is prevention of that first episode of overt hepatic encephalopathy.

So medically controlled ascites, and I think what that means for us in practice is that certain patients with cirrhosis don't have any portal hypertension, and certain patients have really severe portal hypertension, refractory ascites, and hepatorenal syndrome, and they really need a transplant more than anything.

But there are these patients who, just as you mentioned, are at such high risk of developing that first episode of overt hepatic encephalopathy, and I think that's who this trial tried to enroll and focus on.

Dr. Reau:
Yeah, so preventative strategies are really important, but we also know we have some patients with encephalopathy who are difficult to control despite using first-line therapy with combination lactulose and rifaximin, so not necessarily in clinical trials. But what are some of the things that you try when you have a patient where standard of care just isn't quite enough?

Dr. Jesudian:
Yes, so we do have some third-line therapies that you could consider. So zinc is one of those. Many of these patients can be deficient in zinc, or even if they're not, zinc is thought to decrease some of the ammonia neurotoxicity. We could also potentially use ammonia scavengers, like those used for urea cycle disorders, to try and decrease the ammonia in the body in general. We've talked about increasing protein intake. And you could also look for spontaneous portosystemic shunts if the patient has those, to close those in certain situations.

Dr. Reau:
If you take one thing away, be aware of treatment options in the pipeline. Every step towards addressing unmet needs counts, and this was one of them.

Thanks so much, and we'll see you next time.

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Details

Episodes

Presenters

Overview
This series of brief episodes focuses on the early recognition and clinical management of hepatic encephalopathy (HE). Drs. Arun Jesudian and Nancy Reau examine subtle signs that may indicate minimal or covert HE and offer strategies for timely diagnosis. The discussion covers practical tools for detection, the role of nutrition and pharmacologic therapy, and evidence-based approaches to prevent progression and hospitalization. Emerging therapies and ongoing clinical trials are also discussed to highlight future directions in HE treatment.
Commercial Support
This activity is supported by an independent educational grant from Bausch Health US, LLC. 
Disclosure of Relevant Financial Relationships
In accordance with the ACCME Standards for Integrity and Independence, it is the policy of Global Learning Collaborative (GLC) that faculty and other individuals who are in the position to control the content of this activity disclose any real or apparent financial relationships relating to the topics of this educational activity. Global Learning Collaborative (GLC) has full policies in place that have identified and mitigated financial relationships and conflicts of interest to ensure independence, objectivity, balance, and scientific accuracy prior to this educational activity.
The following faculty/staff members have reported financial relationships with ineligible companies within the last 24 months.
Faculty:
Arun B. Jesudian, MD
Professor of Clinical Medicine
Weill Cornell Medicine
New York, NY
Research: Salix Pharmaceuticals
Consulting Fees: Madrigal Pharmaceuticals, Mallinckrodt Pharmaceuticals, Salix Pharmaceutical

Nancy Reau, MD
Chief of Internal Medicine
Rush University Medical Center
Chicago, IL
Research: AbbVie Inc., Gilead Sciences, Inc., Salix Pharmaceuticals
Consulting Fees: Arbutus, Gilead Sciences, Inc., Ipsen, Mallinckrodt Pharmaceuticals
Reviewers/Content Planners/Authors: 
- Cindy Davidson has no relevant relationships to disclose. 
- Rosanne Strauss has no relevant relationships to disclose. 
- Brian P. McDonough, MD, FAAFP, has no relevant relationships to disclose. 
Learning Objectives
Upon completion of this activity, learners should be better able to:
- Explain the clinicalimportance of the onset of MHE
- Differentiate the clinical characteristics of covert HE from overt HE
- Determinean appropriate treatment regimen for a patient with HE
- Summarize data from clinical trials of emerging therapeutic approaches to the treatment of HE
Target Audience
This activity has been designed to meet the educational needs of Gastroenterologists and Hepatologists as well as all other physicians, physician assistants, nurse practitioners, nurses, pharmacists, and healthcare providers involved in managing patients with Hepatic Encephalopathy. 
Accreditation and Credit Designation Statements
In support of improving patient care, Global Learning Collaborative (GLC) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team. 

Global Learning Collaborative (GLC) designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Global Learning Collaborative (GLC) designates this activity for 1.0 nursing contact hour(s). Nurses should claim only the credit commensurate with the extent of their participation in the activity.

Global Learning Collaborative (GLC) designates this activity for 1.0 contact hour(s)/0.1 CEUs of pharmacy contact hour(s).

The Universal Activity Number for this program is JA0006235-0000-25-139-H01-P. This learning activity is knowledge-based. Your CE credits will be electronically submitted to the NABP upon successful completion of the activity. Pharmacists with questions can contact NABP customer service (custserv@nabp.net). 

Global Learning Collaborative (GLC) has been authorized by the American Academy of PAs (AAPA) to award AAPA Category 1 CME credit(s) for activities planned in accordance with AAPA CME Criteria. This activity is designated for 1.0 AAPA Category 1 CME credit(s). Approval is valid until December 12, 2026. PAs should claim only the credit commensurate with the extent of their participation in the activity.
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Disclaimer
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information.
Reproduction Prohibited Reproduction of this material is not permitted without written permission from the copyright owner. 
System Requirements
- Supported Browsers (2 most recent versions):
- - Google Chrome for Windows, Mac OS, iOS, and Android
  - Apple Safari for Mac OS and iOS
  - Mozilla Firefox for Windows, Mac OS, iOS, and Android
  - Microsoft Edge for Windows
- Recommended Internet Speed: 5Mbps+
Publication Dates
Release Date: 12/11/2025
Expiration Date: 12/11/2026