New score challenges old predictors
"MERAGE has superior performance for predicting return to drinking (RTD) compared to HRAR in AH."
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11/20/2025
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by Kerri Miller
The MERAGE score—encompassing Model for End-Stage Liver Disease (MELD), Ethnicity, Race, Age, Gender, and Education—achieved an area under the receiver operating characteristic curve (AUROC) of 0.69 in the validation cohort compared with 0.54 for the High-Risk Alcohol Relapse (HRAR) scale in patients hospitalized for alcohol-associated hepatitis (AH), according to research presented at the annual meeting of the American Association for the Study of Liver Diseases.
"MERAGE has superior performance for predicting return to drinking (RTD) compared to HRAR in AH, as demonstrated through independent validation," the researchers reported. "Including age, race/ethnicity, education, and MELD significantly improve the discriminant power."
The multicenter prospective observational cohort analyzed 347 patients with AH diagnosed per National Institute on Alcohol Abuse and Alcoholism consensus criteria, of whom 98 (28%) returned to drinking within 200 days of follow-up. The mean age was 45 years, with 43% female patients and 84% non-Hispanic White patients. Mean baseline MELD score was 25.
Patients who returned to drinking demonstrated greater numbers of daily drinks (12.7 vs 9.7), more drinking days (21.3 vs 13.6), and greater total drinks in the past 30 days (242.4 vs 133.6) compared with those who maintained abstinence. Baseline MELD scores were slightly lower in the return-to-drinking group (23.3 vs 24.9).
The HRAR scale, originally developed for liver transplantation candidates, incorporates duration of heavy drinking, number of daily drinks, and prior admissions to alcohol use disorder treatment programs. However, its utility in AH patients not undergoing transplantation remained unvalidated.
Researchers employed generalized additive models to capture nonlinear and interactive effects of drinking variables, with typical numbers of daily drinks and drinking days in the past 30 days included as a bivariate function. The bivariate analysis revealed return-to-drinking risk increased substantially in patients with more than 20 drinking days, particularly among those with higher daily intake. Data were split 70% to 30% for model training and validation.
Using an optimal threshold of 0.242 determined by Youden Index, MERAGE demonstrated sensitivity of 0.71, specificity of 0.60, positive predictive value of 0.34, and negative predictive value of 0.88 in the validation sample. By comparison, HRAR (optimal threshold=1.5) showed sensitivity of 0.38, specificity of 0.65, positive predictive value of 0.24, and negative predictive value of 0.78.
MERAGE also demonstrated improved overall predictive accuracy (62% vs 59%) compared with HRAR in the validation cohort. In the training sample, MERAGE showed even stronger performance with AUROC of 0.78 vs 0.55 for HRAR.
"RTD results from multiple clinical and behavioral factors whose nonlinear and interacting influences may determine the level of risk," noted Richard Sterling, MD, of Virginia Commonwealth University, and colleagues.
The researchers acknowledged that independent validation in broader patient populations is needed to establish practical utility.
Author disclosures were not provided in the conference abstract.
Source: AASLD
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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.