CHICAGO – It has been an exciting time to be a hepatologist. During my career, I have witnessed some of the miracles in modern medicine. The most notable is the progress from discovery of the hepatitis C virus (previously non-A, non-B hepatitis) in 1989 to a near 100% cure with 8-12 weeks of oral medications in just 30 years, culminating in the The Nobel Prize in Physiology or Medicine in 2020.
This remarkable feat is matched by the progress from discovery of the hepatitis B virus (initially coined Australia antigen) and a 1976 Nobel Prize to an effective vaccine in 1981, to a list of antiviral drugs approved beginning in 1992 (with currently available nucleos(t)ide analogues associated with near zero risk of antiviral drug resistance even when used as monotherapy), to demonstration that both hepatitis B vaccine and antivirals can prevent liver cancer. Other major breakthroughs include blood-based and image-based noninvasive assessment of liver fibrosis obviating the need for liver biopsy to stage liver disease, and multiple systemic therapies for advanced liver cancer.
However, there remain many challenges. While we have the tools to eliminate hepatitis B and hepatitis C, resources and coordinated efforts are needed to realize this feasible goal. Development of a vaccine for hepatitis C and a cure for hepatitis B will facilitate this goal.
The biggest present-day challenges in hepatology are the epidemics of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD), particularly since both are increasingly impacting young people, socially disadvantaged populations, and those with mental health problems. Social isolation and mental and financial stressors associated with the COVID pandemic have aggravated both NAFLD and ALD, which have now become the leading indications for liver transplantation. Multi-pronged approaches, including public policies and education, destigmatization, easy access to mental health care, provider training, and provision of multi-disciplinary care, are needed to curb this tsunami. NAFLD affects more than 30% of the global population, and screening with simple biomarker(s) followed by liver stiffness measurement using elastography has been proposed to identify patients with or at high risk of advanced fibrosis or cirrhosis for specialist care. NAFLD is a heterogeneous disease and the requirement for paired liver biopsies to demonstrate benefit have made drug development challenging. Better phenotyping of disease and surrogates for outcomes are needed. Liver cancer is one of the top cancer killers globally, but it is also a preventable cancer making prevention and early treatment of liver disease a top public health priority.
Dr. Lok is director of clinical hepatology and assistant dean for clinical research, University of Michigan Medical School, Ann Arbor. She disclosed research grants with AstraZeneca, Kowa, and Target. She has served as a consultant/adviser to Abbott, Chroma, GlaxoSmithKline, Roche, Virion, and Novo Nordisk. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
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Developed a paper-based colorimetric sensor array for chemical threat detection.
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Can detect 12 chemical agents, including industrial toxins.
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Production cost is under 20 cents per chip.
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Utilizes dye-loaded silica particles on self-adhesive paper.
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Provides rapid, simultaneous identification through image analysis.
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Inspired by the mammalian olfactory system for pattern recognition.
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Future developments include a machine learning-enabled reader device.
The guidelines emphasize four-hour gastric emptying studies over two-hour testing. How do you see this affecting diagnostic workflows in practice?
Dr. Staller: Moving to a four-hour solid-meal scintigraphy will actually simplify decision-making. The two-hour reads miss a meaningful proportion of delayed emptying; standardizing on four hours reduces false negatives and the “maybe gastroparesis” purgatory that leads to repeat testing. Practically, it means closer coordination with nuclear medicine (longer slots, consistent standardized meal), updating order sets to default to a four-hour protocol, and educating front-line teams so patients arrive appropriately prepped. The payoff is fewer equivocal studies and more confident treatment plans.
Metoclopramide and erythromycin are the only agents conditionally recommended for initial therapy. How does this align with what is being currently prescribed?
Dr. Staller: This largely mirrors real-world practice. Metoclopramide remains the only FDA-approved prokinetic for gastroparesis, and short “pulsed” erythromycin courses are familiar to many of us—recognizing tachyphylaxis limits durability. Our recommendation is “conditional” because the underlying evidence is modest and patient responses are heterogeneous, but it formalizes what many clinicians already do: start with metoclopramide (lowest effective dose, limited duration, counsel on neurologic adverse effects) and reserve erythromycin for targeted use (exacerbations, bridging).
Several agents, including domperidone and prucalopride, received recommendations against first-line use. How will that influence discussions with patients who ask about these therapies?
Dr. Staller: Two points I share with patients: evidence and access/safety. For domperidone, the data quality is mixed, and US access is through an FDA IND mechanism; you’re committing patients to EKG monitoring and a non-trivial administrative lift. For prucalopride, the gastroparesis-specific evidence isn’t strong enough yet to justify first-line use. So, our stance is not “never,” it’s just “not first.” If someone fails or cannot tolerate initial therapy, we can revisit these options through shared decision-making, setting expectations about benefit, monitoring, and off-label use. The guideline language helps clinicians have a transparent, evidence-based conversation at the first visit.
The guidelines suggest reserving procedures like G-POEM and gastric electrical stimulation for refractory cases. In your practice, how do you decide when a patient is “refractory” to medical therapy?
Dr. Staller: I define “refractory” with three anchors.
1. Adequate trials of foundational care: dietary optimization and glycemic control; an antiemetic; and at least one prokinetic at appropriate dose/duration (with intolerance documented if stopped early).
2. Persistent, function-limiting symptoms: ongoing nausea/vomiting, weight loss, dehydration, ER visits/hospitalizations, or malnutrition despite the above—ideally tracked with a validated instrument (e.g., GCSI) plus nutritional metrics.
3. Objective correlation: delayed emptying on a standardized 4-hour solid-meal study that aligns with the clinical picture (and medications that slow emptying addressed).
At that point, referral to a center with procedural expertise for G-POEM or consideration of gastric electrical stimulation becomes appropriate, with multidisciplinary evaluation (GI, nutrition, psychology, and, when needed, surgery).
What role do you see dietary modification and glycemic control playing alongside pharmacologic therapy in light of these recommendations?
Dr. Staller: They’re the bedrock. A small-particle, lower-fat, calorie-dense diet—often leaning on nutrient-rich liquids—can meaningfully reduce symptom burden. Partnering with dietitians early pays dividends. For diabetes, tighter glycemic control can improve gastric emptying and symptoms; I explicitly review medications that can slow emptying (e.g., opioids; consider timing/necessity of GLP-1 receptor agonists) and encourage continuous glucose monitor-informed adjustments. Pharmacotherapy sits on top of those pillars; without them, medications will likely underperform.
The guideline notes “considerable unmet need” in gastroparesis treatment. Where do you think future therapies or research are most urgently needed?
Dr. Staller: I see three major areas.
1. Truly durable prokinetics: agents that improve emptying and symptoms over months, with better safety than legacy options (e.g., next-gen motilin/ghrelin agonists, better-studied 5-HT4 strategies).
2. Endotyping and biomarkers: we need to stop treating all gastroparesis as one disease. Clinical, physiologic, and microbiome/omic signatures that predict who benefits from which therapy (drug vs G-POEM vs GES) would transform care.
3. Patient-centered trials: larger, longer RCTs that prioritize validated symptom and quality-of-life outcomes, include nutritional endpoints, and reflect real-world medication confounders.
Our guideline intentionally highlights these gaps to hopefully catalyze better trials and smarter referral pathways.
Dr. Staller is with the Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston.