Positive trends in chronic HCV mortality
“DAAs have revolutionized the management of HCV by making it a curable disease.”
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11/21/2025
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by Doug Brunk
Since the introduction of direct-acting antiviral (DAA) therapies in 2014, mortality from hepatitis C-related cirrhosis has declined by about 8.2% per year, according to an analysis of public health data.
“DAAs have revolutionized the management of HCV by making it a curable disease,” presenting author Ashraf Ullah, MD, an internal medicine resident at Guthrie Robert Packer Hospital, Pennsylvania, and colleagues wrote in an abstract presented during the annual meeting of the American Association for the Study of Liver Diseases. “Despite these breakthroughs, hepatitis C remains a significant public health burden in the United States, particularly among historically underserved populations. Understanding mortality trends over time can provide critical insight into the effectiveness of public health interventions and identify persistent health care disparities.”
The researchers analyzed U.S. mortality data from the CDC WONDER database, focusing on cirrhosis as the underlying cause of death and hepatitis C virus (HCV) as a contributing cause. They calculated age-adjusted mortality rates per 100,000 and used Joinpoint regression to identify trends, focusing on annual percentage changes (APCs) from 1999 to 2023.
From 1999 to 2024, HCV-related cirrhosis accounted for 175,712 deaths. Mortality rates rose from 2.9 in 1999 to 3.8 in 2013, but things changed after DAAs were introduced. Rates began to fall, dropping from 3.8 in 2014 to 2.3 in 2024, an 8.2% decrease each year. Men consistently had higher mortality rates than women. For men, rates increased by about 1.5% per year until 2014, then fell by 9% annually through 2021. For women, rates went up by 1.4% each year until 2013 and then declined by 8.8% annually from 2014 to 2019.
In other findings, mortality rates began to decline across all racial groups after 2013, with the steepest decline seen in non-Hispanic Black populations (APC: -11%). In 2022, non-Hispanic American Indian/Alaska Native populations had the highest mortality rate (5.1 per 100,000), followed by Hispanics (2.5 per 100,000), non-Hispanic Black (2.4 per 100,000), non-Hispanic White (1.7 per 100,000), and non-Hispanic Asian populations (0.8 per 100,000).
Mortality rates for HCV were highest among men, people aged 55–74, American Indian or Alaska Native individuals, those living in the Western U.S., and residents of medium to small metropolitan areas.
The researchers did not disclose any conflicts of interest.
Source: AASLD
Summary content
7 Key Takeaways
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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.