GHAPPcast

In this GHAPP podcast episode, Jordan Mayberry, PA-C, and Patrick Horne, NP, dive deep into the complexities of chronic liver disease and its progression to cirrhosis. Drawing on over 11 years of experience in hepatology, Jordan and Patrick discuss the most common causes of liver disease, including viral hepatitis (Hepatitis B & C), alcohol-related liver disease, and metabolic-associated steatotic liver disease (MASLD) and metabolic-associated steatohepatitis (MASH). They explore the increasing prevalence of these conditions and how the rise in diagnoses is reshaping treatment strategies across the country.

Through their discussion, they explain how chronic liver diseases gradually progress, starting with liver inflammation that leads to fibrosis and eventually to cirrhosis. Understanding this progression is crucial for proper staging of liver disease and determining the right treatment approach. The episode emphasizes the importance of early diagnosis and monitoring, especially as patients transition from compensated cirrhosis (where they show no major complications) to decompensated cirrhosis, which involves severe complications like jaundice, ascites, and hepatic encephalopathy.

Special focus is given to hepatocellular carcinoma (HCC), a major risk in patients with cirrhosis. Jordan and Patrick outline the vital screening practices, including ultrasound imaging and alpha-fetoprotein testing, to detect early-stage liver cancer. With HCC being a cumulative risk, they stress the importance of regular screenings for cirrhotic patients, and the impact early detection can have on treatment outcomes, including potential liver transplant and localized therapies.

Moreover, the hosts emphasize the need for patient education—especially for those newly diagnosed with cirrhosis. Teaching patients to recognize early signs of complications ensures timely intervention and better management of their condition. Jordan and Patrick discuss how healthcare providers can play a key role in improving patient care by educating patients about the disease process, the importance of regular check-ups, and the monitoring protocols that can help manage cirrhosis and prevent further complications.

Whether you’re in hepatology practice or involved in the care of liver disease patients, this episode provides practical, actionable insights for managing chronic liver diseases and cirrhosis effectively. For more resources, visit the GHAPP website or download the GHAPP ACE app for the latest updates in liver disease management.

Thank you to Johnson & Johnson for your support of this Medication Review Video Module.

In this medication review video module, Anne Feldman, NP, from the Cleveland Clinic Foundation, provides an in-depth overview of Guselkumab, an FDA-approved treatment for moderately to severely active ulcerative colitis. Anne explains the mechanism of action of Guselkumab, which is a dual-action monoclonal antibody that targets key pro-inflammatory proteins and their receptors, disrupting the inflammatory cascade responsible for chronic inflammation in conditions like ulcerative colitis, psoriasis, and psoriatic arthritis.

This monoclonal antibody therapy works by inhibiting the IL-23 protein, which plays a pivotal role in immune system activation and inflammation. Guselkumab reduces disease activity and promotes tissue healing by blocking the effects of IL-23, making it an effective treatment option for patients with ulcerative colitis.

Anne also outlines the dosing regimen for Guselkumab, starting with induction doses of 200 mg IV at weeks 0, 4, and 8, followed by maintenance doses either 200 mg every 4 weeks or 100 mg every 8 weeks, depending on the patient's response. It is administered in an infusion center, taking approximately one hour per infusion. Guselkumab is soon expected to be FDA-approved for Crohn’s disease, offering a first-line advanced therapy option or as a subsequent therapy after failure of other treatments.

Safety considerations are highlighted, including the need for vaccination and tuberculosis screening prior to starting the therapy. Patients on Guselkumab should avoid live vaccines due to its potential to suppress the immune system, which can increase the risk of infections. Common side effects include respiratory infections, sore throat, headaches, and injection site reactions. Guselkumab is not approved for use in pediatric patients (under 18 years of age), and its safety during pregnancy or breastfeeding is not fully established.

This detailed review provides essential information for healthcare providers and patients considering Guselkumab as part of their treatment for ulcerative colitis and other autoimmune diseases. For further information, visit the GHAPP website or download the GHAPP ACE app.

Thank you to Johnson & Johnson for your support of this GHAPPcast episode.

In this insightful episode of GHAPPcast, the official podcast of the Gastroenterology and Hepatology Advanced Practice Providers, host Gabriella McCarty, NP-C, delves into the complex yet critical topic of CD64 positive binding and its relevance in inflammatory bowel disease (IBD) treatment, particularly in relation to Interleukin-23 (IL-23) inhibition. Gabriella is joined by Andrea Banty, NP, a respected GHAPP faculty member and expert in gastroenterology, who provides valuable insights into the role of CD64 in the immune system and its impact on diseases like Crohn’s disease and ulcerative colitis.

In this episode, Andrea explains how CD64 receptors, found on immune cells, are upregulated during inflammation and can contribute to IL-23 production. This protein plays a significant role in the pathogenesis of IBD and other inflammatory conditions. By targeting CD64 and inhibiting IL-23, therapies may reduce inflammation and promote healing in the GI mucosal lining, improving patient outcomes in ulcerative colitis and Crohn’s disease.

The podcast also discusses current therapies that target IL-23, including those that work at the P40 and P19 subunits, with an exciting focus on the potential of Guselkumab, a therapy that targets IL-23 at the P19 subunit and also binds CD64. This unique dual-action therapy has shown promise for the treatment of psoriasis and psoriatic arthritis and is anticipated to receive FDA approval for the treatment of IBD as well, offering a new avenue for advanced therapy.

As new therapeutic options emerge, Andrea and Gabriella explore the potential clinical applications of CD64 inhibition and IL-23 targeting, emphasizing the importance of personalized care in IBD management. The discussion highlights how advanced practice providers can make informed therapeutic decisions to improve IBD patient outcomes by considering factors such as efficacy, safety, and patient preferences for treatment routes.

This episode is a must-listen for gastroenterology professionals, advanced practice providers, and anyone interested in the evolving landscape of IBD treatment and immune modulation therapies. Visit the GHAPP website or download the GHAPP ACE app for more information.

Thank you to Johnson & Johnson for your support of this FAQ Video Module.

In this informative FAQ video module, Sarah Enslin, a physician assistant at the University of Rochester Medical Center, discusses the role of Interleukin-23 (IL-23) in treating immune-mediated inflammatory diseases, particularly inflammatory bowel disease (IBD). Sponsored by Johnson & Johnson, this video highlights how IL-23 directed therapies have revolutionized the management of IBD, including Crohn’s disease and ulcerative colitis.

Sarah explains how IL-23, primarily produced by dendritic cells and macrophages, is central to the development of TH17 cells, a subset of CD4+ T cells involved in chronic inflammation. In IBD, IL-23 signaling promotes the activation and differentiation of TH17 cells in the intestinal mucosa, which secrete pro-inflammatory cytokines like IL-17, damaging the intestinal barrier, leading to inflammation and disease progression.

One of the leading therapies in this class is Guselkumab, a monoclonal antibody that selectively targets the p19 subunit of IL-23, inhibiting its signaling pathway. By targeting IL-23 without affecting other immune responses (such as IL-12 driven pathways), Guselkumab can reduce TH17 cell activation and the inflammation they cause, leading to improved disease outcomes. This selective blockade not only benefits the gut but also extends to skin and joints, offering a comprehensive approach to treating IBD.

Clinical trials have demonstrated the efficacy of IL-23 directed therapies, with patients experiencing significant reductions in disease severity, improved clinical symptoms, and an overall enhanced quality of life.

This module is a valuable resource for advanced practice providers, including physician assistants and nurse practitioners, who are looking to expand their knowledge on the latest IBD treatment advancements and IL-23 inhibition therapies. For more information visit the GHAPP website or download the GHAPP ACE app.

Thank you to Johnson & Johnson for your support of this Journal Club Video Module.

In this Journal Club video module, Shayla Scheonoff, a physician assistant from Rochester, Minnesota, provides a comprehensive review of the efficacy and safety of Guselkumab induction therapy for moderately to severely active ulcerative colitis (UC). Sponsored by Johnson & Johnson, this detailed analysis covers both the Phase 2B and Phase 3 QUASAR induction studies for Guselkumab, a dual-acting IL-23 p19 subunit inhibitor that blocks IL-23 and binds to CD64 on cells that produce IL-23. Previously approved for psoriasis and psoriatic arthritis, Guselkumab has shown remarkable promise as a treatment for ulcerative colitis.

The Phase 2B study involved 313 patients with severe UC who had failed previous therapies. Results showed that 61% of patients receiving Guselkumab 200 mg and 60% of patients receiving Guselkumab 400 mg achieved a clinical response at 12 weeks, significantly outperforming the placebo group, where only 27% responded. The study also demonstrated that Guselkumab was well-tolerated, with a 1% rate of serious adverse events compared to 5.7% in the placebo group. The Phase 3 QUASAR study further confirmed Guselkumab's effectiveness, with 22.6% of patients achieving clinical remission at week 12, compared to 7.9% in the placebo group. Secondary endpoints like symptomatic remission, endoscopic improvement, and histologic improvement also showed significant benefits for patients on Guselkumab.

The Guselkumab induction therapy demonstrated consistent safety profiles in both studies, with similar rates of infection and serious infections across both treatment and placebo arms. This Journal Club video provides an in-depth look at the promising results of Guselkumab in treating moderately to severely active ulcerative colitis, offering an innovative therapy option for patients who have not responded to traditional treatments.

For more information on Guselkumab and its role in the treatment of ulcerative colitis, visit the GHAPP website or GHAPP ACE mobile app and access additional resources tailored for advanced practice providers.

Thank you to Johnson & Johnson for your support of this Medication Review Video Module.

Clinical trials play a crucial role in guiding treatment decisions, but the way missing data is handled can significantly impact the results. In this medication review video module, Whitney Steinmetz, NP, from Presbyterian Medical Group in Albuquerque, NM, explains the concept of non-responder imputation (NRI)—a widely used statistical method in clinical trials.

Non-responder imputation is a conservative approach used to address missing data by assuming that participants who drop out or have missing responses did not respond to treatment. This method helps prevent overestimating a therapy’s effectiveness, ensuring that clinical trial results remain reliable. However, it can also underestimate a treatment’s true impact, particularly if patients drop out for reasons unrelated to treatment failure. Understanding how this statistical method influences trial outcomes is essential for healthcare providers, as it directly affects the interpretation of treatment efficacy and patient care decisions.

By reducing bias and offering a straightforward approach to data analysis, non-responder imputation helps maintain the integrity of clinical trial results. However, its conservative nature can sometimes skew findings, making a treatment appear less effective than it actually is. This is why it’s important for clinicians to be aware of how missing data is managed in studies. If non-responder imputation was used, the reported effectiveness of a treatment might be a cautious estimate rather than a complete reflection of its potential benefits.

For more information please visit the GHAPP website or download the GHAPP ACE app.

Thank you to Johnson & Johnson for your support of this FAQ Video Module.

Inflammatory Bowel Disease (IBD) is a complex condition influenced by genetic, environmental, and microbial factors. In this FAQ video module, Amy Stewart, ARNP, from Capital Digestive Care in Washington, DC, explains the critical role of the IL-23/IL-17 axis in the pathogenesis of IBD. Supported by Johnson & Johnson, this discussion explores the cytokine-driven inflammatory pathways that contribute to chronic intestinal inflammation and how they can be targeted for effective treatment.

IL-23 (Interleukin-23) is a pro-inflammatory cytokine primarily produced by macrophages and dendritic cells in response to microbial stimulation. It plays a pivotal role in promoting chronic inflammation in IBD by inducing a unique inflammatory gene signature. This leads to the differentiation of T-helper 17 (Th17) cells, a specialized subset of T cells that drive inflammation. The activation of IL-23 receptors triggers a cascade of immune responses through the JAK-STAT signaling pathway, further amplifying the inflammatory process. Additionally, IL-17, a key cytokine regulated by IL-23, plays a major role in neutrophil activation and immune modulation, influencing both infection resistance and autoimmune pathology.

Given the central role of the IL-23/IL-17 axis in IBD and other autoimmune diseases, understanding these inflammatory pathways is crucial for developing targeted therapies. Many modern biologic treatments for IBD are designed to modulate these specific cytokines, helping to reduce inflammation and improve patient outcomes.

Join Amy Stewart, NP, in this expert discussion to gain deeper insights into the IL-23/IL-17 pathway and its implications for IBD treatment strategies. For more information and to explore the latest advancements in IBD care, visit the GHAPP website.

Thank you to Johnson & Johnson for your support of this FAQ Video Module.

Welcome to this FAQ video module, proudly supported by Johnson & Johnson. In this educational session, Erica Heagy, NP, from Alaska Digestive and Liver Disease, explores the IL-23/IL-17 axis, a crucial pathway in the pathogenesis of inflammatory bowel disease (IBD), psoriasis, psoriatic arthritis, multiple sclerosis, and other immune-mediated disorders.

The IL-23 cytokine plays a pivotal role in promoting Th17 cell differentiation, which in turn produces pro-inflammatory cytokines like IL-17A, IL-17F, tumor necrosis factor (TNF), and IL-6. IL-17, a key driver of chronic inflammation, is overexpressed in patients with autoimmune diseases, contributing to tissue damage, immune dysregulation, and inflammation. These effects are particularly evident in conditions such as Crohn’s disease, ulcerative colitis, and psoriatic arthritis, making the IL-23/IL-17 axis a major target for emerging biologic therapies.

Therapeutic strategies that block IL-23 or its receptor have been FDA-approved for treating psoriasis, psoriatic arthritis, and IBD. By inhibiting this inflammatory pathway, these treatments help reduce disease progression, alleviate symptoms, and improve patient outcomes. Understanding this mechanism is essential for healthcare providers seeking optimized, targeted treatment options for their patients.

For more information on IL-23-targeted therapies and advances in gastroenterology, hepatology, and immune-mediated disease treatment, visit GHAPP.org or download the GHAPP ACE mobile app on Android or IOS. Stay connected with us on LinkedIn, YouTube, X (formerly Twitter), and Instagram for expert insights and updates.

Thank you to Johnson & Johnson for your support of this GHAPPcast episode.

Welcome to GHAPPcast, the official podcast of Gastroenterology and Hepatology Advanced Practice Providers (GHAPP), where we delve into the latest advancements in GI and liver diseases. In this enlightening episode, host Gabriella McCarty, NP-C, from NorthShore Gastroenterology, explores the intricate role of the IL-23/IL-17 axis in inflammatory bowel disease (IBD). This discussion, supported by Johnson & Johnson, offers invaluable insights into how this immunological pathway influences IBD progression and how targeted therapies are shaping the future of treatment.

Joining the conversation is Allison Krustapentus, NP, from Beth Israel Deaconess Medical Center, an expert in IBD patient care and immunology. Together, they break down the IL-23/IL-17 signaling cascade, explaining its impact on immune-mediated inflammation and how disruptions in this pathway contribute to chronic GI conditions like Crohn’s disease and ulcerative colitis. They discuss how IL-23 promotes Th17 cell differentiation, leading to IL-17-driven inflammation, which, when dysregulated, fuels tissue damage, immune overactivity, and chronic inflammation in IBD.

This episode also highlights the therapeutic implications of targeting the IL-23/IL-17 pathway. With the rise of precision medicine, newer biologics are offering more effective, patient-specific treatments that can slow disease progression and improve patient outcomes. The discussion also covers shared decision-making in patient care, emphasizing the importance of educating patients about their disease and available treatment options.

Subscribe to GHAPPcast on your favorite podcast platform for in-depth discussions on IBD, hepatology, and GI innovations. Visit GHAPP.org, download the GHAPP ACE app and follow us on LinkedIn, YouTube, X (formerly Twitter), and Instagram for our latest updates and expert insights.

Thank you to Johnson & Johnson for your support of this Medication Review Video Module.

In this medication review, Whitney Steinmetz, NP, from Presbyterian Medical Group in Albuquerque, New Mexico, explores the mechanism of action of Guselkumab, a promising monoclonal antibody therapy for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD).

IBD is driven by chronic gastrointestinal inflammation, resulting from a complex interplay of genetic predisposition, environmental triggers, and immune system dysregulation. A crucial element in this inflammatory process is interleukin-23 (IL-23), a pro-inflammatory cytokine that promotes the differentiation, expansion, and survival of Th17 cells. These Th17 cells produce additional inflammatory cytokines, such as IL-17 and IL-22, which contribute to intestinal inflammation and disease progression.

Guselkumab, a monoclonal antibody therapy, specifically targets the p19 subunit of IL-23, preventing its interaction with the IL-23 receptor on T cells. By blocking IL-23 signaling, Guselkumab reduces Th17 cell activation and cytokine production, leading to a decrease in gut inflammation. This mechanism positions Guselkumab as a promising treatment option for IBD, aiming to mitigate chronic inflammation, improve mucosal healing, and enhance patient outcomes.

For more information on IL-23 inhibitors, biologic therapies, and advancements in gastroenterology, visit GHAPP.org or download the GHAPP ACE app on IOS and Android. Follow us on LinkedIn, YouTube, X (Twitter), and Instagram for the latest updates and expert insights.