Clinical Programs Update

Celiac disease is a prevalent autoimmune disorder affecting approximately 1 in 100 people globally. In those with this condition, the immune system reacts adversely to gluten—a protein found in many grains—resulting in inflammation and damage to the small intestine. This can lead to distressing symptoms such as abdominal pain, nausea, and diarrhea.

When patients present with these symptoms, Dr. Nielsen Fernandez-Becker, head of Stanford Health Care’s celiac disease program, often relies on blood tests and intestinal biopsies for diagnosis. However, these tests can be hit or miss, especially if patients have already eliminated gluten from their diets, which can mask signs of intestinal damage. There is no fool proof test to diagnose celiac disease in patients already on a gluten free diet without re-introducing gluten.

Hope is on the horizon! Dr. Fernandez-Becker and his collaborator, Dr. Chaitan Khosla, a professor of chemistry at Stanford, are pioneering a novel approach to celiac detection with support from Stanford’s Innovative Medicines Accelerator (IMA). They recently launched a clinical trial using HB2121, a fluorescent compound that illuminates a specific molecule linked to celiac disease. This innovative method allows for clear identification of active tissue transglutaminase 2 (TG2) during endoscopic procedures, providing definitive answers about gluten's role in a patient's symptoms. Furthermore, it may be an important tool for monitoring the health of the small intestine over time. Finally, the mechanism of action of this has the potential to treat celiac disease, offering a promising non-dietary therapy.

The trial aims to enhance diagnosis, monitor disease progression, and evaluate treatment efficacy. With this groundbreaking fluorescent probe, the team hopes to revolutionize celiac disease management, offering patients a clearer understanding of their condition and the effectiveness of their gluten-free diet.

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Celiac disease is a prevalent autoimmune disorder affecting approximately 1 in 100 people worldwide. In individuals with this condition, the immune system reacts adversely to gluten, a protein found in many grains, leading to inflammation and damage in the small intestine. This can result in distressing symptoms such as abdominal pain, nausea, and diarrhea.

When patients present with these symptoms, Dr. Nielsen Fernandez-Becker, head of Stanford Health Care’s celiac disease program, often relies on blood tests and intestinal biopsies for diagnosis. However, these tests can be unreliable, particularly if patients have already eliminated gluten from their diets, which can obscure signs of intestinal damage. Currently, there is no foolproof method to diagnose celiac disease in patients on a gluten-free diet without reintroducing gluten.

But hope is on the horizon! Dr. Fernandez-Becker and his collaborator, Dr. Chaitan Khosla, a professor of chemistry at Stanford, are pioneering a novel approach to celiac detection with support from Stanford’s Innovative Medicines Accelerator (IMA). They have recently launched a clinical trial using HB2121, a fluorescent compound that binds to active tissue transglutaminase 2 (TG2)—the enzyme central to celiac disease that modifies gluten into a toxic form. This innovative method allows for the clear identification of active TG2 during endoscopic procedures, providing definitive answers about gluten's role in a patient's symptoms.

Moreover, HB2121 not only has diagnostic potential but also serves as a valuable tool for monitoring the health of the small intestine over time. Its mechanism of action may even offer a promising non-dietary treatment for celiac disease.

The trial aims to enhance diagnosis, monitor disease progression, and evaluate treatment efficacy. With this groundbreaking fluorescent probe, the team hopes to revolutionize celiac disease management, providing patients with a clearer understanding of their condition and the effectiveness of their gluten-free diet.

Through the integration of clinical excellence and translational innovation, Stanford’s Celiac Disease Clinical Program is redefining how this condition is diagnosed, managed, and studied. The team’s ultimate goal is to empower patients with clearer answers, personalized care, and improved quality of life thus bringing us closer to a future where celiac disease can be detected earlier, treated more effectively, and, one day, cured.

The use of liver grafts from donors after circulatory death (DCD) has been part of liver transplantation practice for more than two decades but remained underutilized until recently. Historically, two major complications limited broader adoption: (1) primary non-function (PNF), an immediate post-transplant graft failure due to severe ischemic injury, and (2) ischemic cholangiopathy (IC), a biliary complication that typically manifests within 1–3 months after transplant and often necessitates re-transplantation.

Both complications stem from ischemic injury that occurs after withdrawal of life-sustaining therapy but before organ perfusion with preservation solutions. As experience accumulated, transplant centers developed strategies to reduce these risks, most notably careful graft selection based on donor warm ischemia time—the interval between withdrawal of support and cold perfusion—and improved donor–recipient matching. These refinements significantly decreased the incidence of PNF.

However, IC continued to represent a major barrier to wider use of DCD grafts, with historical rates as high as 15–20%. The introduction of normothermic machine perfusion (NMP) has been transformative, allowing continuous oxygenated blood flow and metabolic assessment of graft viability prior to implantation. NMP has reduced the rate of IC to below 5% in several recent series, bringing post-transplant outcomes closer to those achieved with donation-after-brain-death grafts.

The broader implementation of NMP, together with refinements in allocation policy and surgical technique, has led to a steady increase in DCD liver transplantation across the United States (Figure 1). At Stanford University, DCD grafts were incorporated into our program beginning in 2023, aligning with national trends. Although our utilization rate remains slightly below the national average, we have already observed marked reductions in waitlist time and waitlist mortality over the past three years (Figure 2). These gains have become particularly evident in 2025 as experience and confidence with the technique have grown.

While DCD grafts continue to carry a small but measurable risk of IC, their use represents a strategic advance to expand access to transplantation and reduce mortality among patients with end-stage liver disease. Importantly, current national allocation discussions include potential prioritization for patients who develop IC following DCD transplantation, offering an additional safeguard that supports continued expansion of this lifesaving practice.

With advances in organ preservation and donor selection, the risk profile of these grafts has shifted significantly. Early referral of appropriate candidates—even those with borderline liver function or previously long wait times—can now improve the likelihood of timely transplantation. Our team welcomes collaboration to identify patients who may benefit from these expanded donor opportunities.