GI and Hepatology News

The US National Institute of Standards and Technology (NIST) has developed precisely measured human fecal material to foster a new era in gut microbiome research. 

According to AGA’s Center for Gut Microbiome Research & Education, this critical resource will help advance the utility and reproducibility of microbiome-based diagnostics — “which still remain relatively meaningless clinically, although patients continue to buy direct-to-consumer tests, and a standard reference material will mean there’s a better way to ensure quality control and accuracy.” 

Though not a therapeutic, Human Fecal Material RM is expected to speed up gastrointestinal (GI) therapeutics since many microbiome-based drugs are inspired by fecal transplants with human stool as the developmental starting point. A standardized reference material will be an important resource as industry develops and tests new drugs. It can be purchased online at the NIST Store (shop.nist.gov).

The product consists of eight frozen vials of exhaustively studied human feces suspended in aqueous solution. Available are more than 25 pages of data identifying the key microbes and biomolecules in the material. Scientists, including those working at biopharmaceutical and biotech companies, can use this material to further their research and develop new drugs that target the microbiome, including treatments that contain living bacteria. 

 

Development

According to NIST, the stool material is “the most precisely measured, scientifically analyzed, and richly characterized human fecal standard ever produced. 

“The project ran for about 6 years from start to finish, the last 2 for manufacturing, characterization, and writing,” said NIST molecular geneticist Scott A. Jackson, PhD, who helped develop the product. “We hope our reference material will lay the foundation for gut microbiome research to thrive and reach its full potential.” 

As founder of NIST’s Complex Microbial Systems Group, Jackson is leading international efforts to improve microbiome and metagenomic measurements by organizing inter-lab studies and refining reference materials and methods. 

The project collected stool from two cohorts of donors, ie, vegetarians and omnivores, with each cohort comprising four to six donors. Material from each cohort was pooled and homogenized before being aliquoted into 5000 vials per cohort. About 300 tubes from each cohort were picked, and aliquots then underwent multiomic analyses. 

Offering his perspective on the new product, Sudhir K. Dutta, MBBS, associate professor in the Division of Gastroenterology and Hepatology at Johns Hopkins University School of Medicine, Baltimore, said, “This tool will be 100% useful for microbiome research.”

And according to Lori Holtz, MD, MSPH, professor of pediatric gastroenterology, hepatology, and nutrition at Washington University School of Medicine in St. Louis, Missouri, the material will aid microbiome research by allowing interpretability and repeatability across studies. “Microbiome research is a relatively new field, and protocols differ from group to group and lab to lab, so it’s been difficult to compare results across studies,” she told GI & Hepatology News. “A standard stool product will allow for greater comparability in preclinical studies and later clinical trials testing interventions to alter the microbiome.”

The NIST developers are looking forward to reaction from the GI research community. “Over the last several years, we’ve released smaller pilot batches of material to smaller groups of stakeholders,” said Jackson. “We’ve used the feedback on these earlier batches to inform the manufacturing and characterization of the final batch that was released in March, but we don’t yet have any feedback yet on the current material.”

Jackson, Dutta, and Holtz disclosed having no relevant competing interests.

A version of this article appeared on Medscape.com.

The US National Institute of Standards and Technology (NIST) has developed precisely measured human fecal material to foster a new era in gut microbiome research. 

According to AGA’s Center for Gut Microbiome Research & Education, this critical resource will help advance the utility and reproducibility of microbiome-based diagnostics — “which still remain relatively meaningless clinically, although patients continue to buy direct-to-consumer tests, and a standard reference material will mean there’s a better way to ensure quality control and accuracy.” 

Though not a therapeutic, Human Fecal Material RM is expected to speed up gastrointestinal (GI) therapeutics since many microbiome-based drugs are inspired by fecal transplants with human stool as the developmental starting point. A standardized reference material will be an important resource as industry develops and tests new drugs. It can be purchased online at the NIST Store (shop.nist.gov).

The product consists of eight frozen vials of exhaustively studied human feces suspended in aqueous solution. Available are more than 25 pages of data identifying the key microbes and biomolecules in the material. Scientists, including those working at biopharmaceutical and biotech companies, can use this material to further their research and develop new drugs that target the microbiome, including treatments that contain living bacteria. 

 

Development

According to NIST, the stool material is “the most precisely measured, scientifically analyzed, and richly characterized human fecal standard ever produced. 

“The project ran for about 6 years from start to finish, the last 2 for manufacturing, characterization, and writing,” said NIST molecular geneticist Scott A. Jackson, PhD, who helped develop the product. “We hope our reference material will lay the foundation for gut microbiome research to thrive and reach its full potential.” 

As founder of NIST’s Complex Microbial Systems Group, Jackson is leading international efforts to improve microbiome and metagenomic measurements by organizing inter-lab studies and refining reference materials and methods. 

The project collected stool from two cohorts of donors, ie, vegetarians and omnivores, with each cohort comprising four to six donors. Material from each cohort was pooled and homogenized before being aliquoted into 5000 vials per cohort. About 300 tubes from each cohort were picked, and aliquots then underwent multiomic analyses. 

Offering his perspective on the new product, Sudhir K. Dutta, MBBS, associate professor in the Division of Gastroenterology and Hepatology at Johns Hopkins University School of Medicine, Baltimore, said, “This tool will be 100% useful for microbiome research.”

And according to Lori Holtz, MD, MSPH, professor of pediatric gastroenterology, hepatology, and nutrition at Washington University School of Medicine in St. Louis, Missouri, the material will aid microbiome research by allowing interpretability and repeatability across studies. “Microbiome research is a relatively new field, and protocols differ from group to group and lab to lab, so it’s been difficult to compare results across studies,” she told GI & Hepatology News. “A standard stool product will allow for greater comparability in preclinical studies and later clinical trials testing interventions to alter the microbiome.”

The NIST developers are looking forward to reaction from the GI research community. “Over the last several years, we’ve released smaller pilot batches of material to smaller groups of stakeholders,” said Jackson. “We’ve used the feedback on these earlier batches to inform the manufacturing and characterization of the final batch that was released in March, but we don’t yet have any feedback yet on the current material.”

Jackson, Dutta, and Holtz disclosed having no relevant competing interests.

A version of this article appeared on Medscape.com.

The US National Institute of Standards and Technology (NIST) has developed precisely measured human fecal material to foster a new era in gut microbiome research. 

According to AGA’s Center for Gut Microbiome Research & Education, this critical resource will help advance the utility and reproducibility of microbiome-based diagnostics — “which still remain relatively meaningless clinically, although patients continue to buy direct-to-consumer tests, and a standard reference material will mean there’s a better way to ensure quality control and accuracy.” 

Though not a therapeutic, Human Fecal Material RM is expected to speed up gastrointestinal (GI) therapeutics since many microbiome-based drugs are inspired by fecal transplants with human stool as the developmental starting point. A standardized reference material will be an important resource as industry develops and tests new drugs. It can be purchased online at the NIST Store (shop.nist.gov).

The product consists of eight frozen vials of exhaustively studied human feces suspended in aqueous solution. Available are more than 25 pages of data identifying the key microbes and biomolecules in the material. Scientists, including those working at biopharmaceutical and biotech companies, can use this material to further their research and develop new drugs that target the microbiome, including treatments that contain living bacteria. 

 

Development

According to NIST, the stool material is “the most precisely measured, scientifically analyzed, and richly characterized human fecal standard ever produced. 

“The project ran for about 6 years from start to finish, the last 2 for manufacturing, characterization, and writing,” said NIST molecular geneticist Scott A. Jackson, PhD, who helped develop the product. “We hope our reference material will lay the foundation for gut microbiome research to thrive and reach its full potential.” 

As founder of NIST’s Complex Microbial Systems Group, Jackson is leading international efforts to improve microbiome and metagenomic measurements by organizing inter-lab studies and refining reference materials and methods. 

The project collected stool from two cohorts of donors, ie, vegetarians and omnivores, with each cohort comprising four to six donors. Material from each cohort was pooled and homogenized before being aliquoted into 5000 vials per cohort. About 300 tubes from each cohort were picked, and aliquots then underwent multiomic analyses. 

Offering his perspective on the new product, Sudhir K. Dutta, MBBS, associate professor in the Division of Gastroenterology and Hepatology at Johns Hopkins University School of Medicine, Baltimore, said, “This tool will be 100% useful for microbiome research.”

And according to Lori Holtz, MD, MSPH, professor of pediatric gastroenterology, hepatology, and nutrition at Washington University School of Medicine in St. Louis, Missouri, the material will aid microbiome research by allowing interpretability and repeatability across studies. “Microbiome research is a relatively new field, and protocols differ from group to group and lab to lab, so it’s been difficult to compare results across studies,” she told GI & Hepatology News. “A standard stool product will allow for greater comparability in preclinical studies and later clinical trials testing interventions to alter the microbiome.”

The NIST developers are looking forward to reaction from the GI research community. “Over the last several years, we’ve released smaller pilot batches of material to smaller groups of stakeholders,” said Jackson. “We’ve used the feedback on these earlier batches to inform the manufacturing and characterization of the final batch that was released in March, but we don’t yet have any feedback yet on the current material.”

Jackson, Dutta, and Holtz disclosed having no relevant competing interests.

A version of this article appeared on Medscape.com.

Dear colleagues,

Many of us diagnose and treat patients with Barrett’s esophagus, estimated to affect up to 5.6% of the US adult population. There has been an expanding array of tools to help diagnose and effectively treat Barrett’s esophagus with dysplasia and malignancy. In particular, endoscopic submucosal dissection (ESD) has emerged as an important method for treating early cancer in the gastrointestinal tract.

But how do we incorporate ESD into our algorithm for management, especially with the popularity and effectiveness of endoscopic mucosal resection (EMR)? In this issue of Perspectives we aim to provide context for the use of ESD, as compared with EMR. Dr. Silvio de Melo discusses his preferred EMR technique and its many advantages in the management of BE, including for residual or refractory areas. In contrast, Dr. Mohamed Othman reviews the power of ESD and when we should consider this approach over EMR. We hope these discussions will facilitate your care for patients with Barrett’s esophagus.

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Endoscopic Mucosal Resection: The ‘Workhorse’ for Patient Care

BY SILVIO W. DE MELO JR, MD, AGAF

Barrett’s esophagus (BE) remains an important clinical problem, being one of the modifiable risk factors for esophageal adenocarcinoma. The care for BE is complex and requires several steps to correctly formulate a therapeutic plan. It starts with a proper endoscopic examination. It is recommended to spend at least 1 minute inspecting and evaluating every centimeter of the salmon-colored epithelium, looking for change in vascular pattern, erosions/ulcers, nodules, and/or masses. After the inspection, random biopsies every 1-2 cm plus targeted biopsies will guide you. It is still controversial if the addition of other sampling strategies, such as brushings or confocal endomicroscopy, is needed.

The introduction of radiofrequency ablation (RFA) was paramount in popularizing the treatment options for BE and sunsetting the previous dominant modality, photodynamic therapy (PDT). RFA proved to have a superior clinical efficacy in replacing the intestinal metaplasia/BE with neosquamous epithelium while boosting a much better safety profile, compared with PDT. However, RFA is most efficacious for “flat BE” and it is not an effective, nor recommended, method to treat nodular BE or early cancer, such as carcinoma in situ or nodular high-grade dysplasia. Endoscopic mucosal resection (EMR) is utilized to overcome those limitations.

There are several techniques utilized for EMR:

• The lift and snare technique.
• The snare-in-cap technique.
• The Band-snare technique.

The free-hand submucosal lift and snare is not frequently used in the esophagus. It is difficult to maintain visualization while being confident that one has the whole lesion inside the snare and that the distal (anal side) part of the lesion is free of any unwanted tissue (to minimize complications such as perforations or unwelcomed gastric resections). It is difficult after the first resection to lift an adjacent area, as the fluid easily leaks from the first resected spot, thus removing larger lesions in piece-meal fashion is challenging. This technique can be used in small (in my personal experience, less than 5 mm) lesions, but, given that there are better and safer alternatives, I almost never use this technique for my esophageal EMR cases. I prefer to use the band-snare technique even for lesions under 5 mm.

The snare-in-cap technique has been utilized in the esophagus. In this technique, a cap is attached to the distal end of the scope and the size of the resection is determined by the size of the cap, usually under 1.5 cm. Because of the risk of perforation without previous lifting, it is required that the lesion is lifted with a submucosal fluid, saline or any Food and Drug Administration–approved EMR solution. The lesion is then suctioned inside the cap where the snare had been previously opened inside the cap, the snare is closed, and the tissue is resected. The same limitations regarding the inability to remove larger lesions (greater than 1.5 cm) because of the challenge in lifting the adjacent area applies here. However, the perforation risk for this technique is higher than the traditional lift and the band and snare techniques. Thus, this technique has fallen out of favor for most endoscopists.

The third technique (band-snare EMR) is the one that most endoscopists use for endoscopic mucosal resection. It is a small variation of the already time-tested and very familiar procedure of esophageal variceal band ligation (EVL). There are multiple commercially available kits for esophageal EMR. The kit contains the chamber with the bands and a proprietary hexagonal snare used to resect the specimen.

The advantages of this technique are:

• It is widely commercially available.
• It builds on a familiar procedure, EVL, therefore the learning curve is short.
• The set-up is quick and the procedure can be completed safely and effectively.
• There is no need for injecting the submucosal with a lifting solution.
• Despite the band having a size limitation of 1 cm, one can remove larger lesions by repeating the band and resect process, using the rosette technique.

Band-snare EMR also has limitations:

• There are only six bands on each chamber. Depending on the size of the lesion, one may need to use multiple kits.
• It is not suitable for en bloc resection of lesions greater than 1 cm.

My experience with band EMR is that we can complete the procedure in under 1 hour. The dreaded complication of perforation occurs in under 1% of cases, most bleeding episodes can easily be controlled endoscopically, and the risk of post-EMR stricture is minimal. Therefore, band EMR is the most used technique for esophageal endoscopic resections.

Esophageal EMR is also effective for other indications in BE therapy, such as residual and recurrent BE. Band-snare EMR can be used for an en bloc resection or rosette technique for the areas resistant to ablation therapies with great success and safety.

From a financial standpoint, comparing EMR with endoscopic submucosal dissection (ESD), EMR is the superior strategy given that EMR is widely available, has a much shorter learning curve, has a greater safety profile, is applicable to a wider variety of indications, and has a more favorable return on investment. EMR should be the workhorse for the care of patients with BE, reserving ESD for specific indications.

In summary, there is no “one-size-fits-all” endoscopic therapy in the care of BE. Most Barrett’s patients can be successfully treated with a combination of ablation plus EMR, reserving ESD for select cases.

Dr. de Melo is section chief of gastroenterology at the Orlando VA Healthcare System, Orlando, Florida. He declares no conflicts of interest.

ESD Over EMR for Resecting Esophageal Lesions

BY MOHAMED O. OTHMAN, MD, AGAF

Although endoscopic submucosal dissection (ESD) is the preferred endoscopic resection method in the East, the adoption of this technique in the West, particularly in the United States, has faced many hurdles. Many endoscopists who routinely perform piecemeal endoscopic mucosal resection (EMR) question the utility of ESD, arguing that EMR is just as effective. While this may hold true in certain situations, the global trend in the endoscopic treatment of early esophageal squamous cell carcinoma, nodular Barrett’s esophagus (BE), and early esophageal adenocarcinoma (EAC) has clearly shifted toward ESD. In this perspective, I will summarize why ESD is preferred over EMR for these indications and explore why ESD has yet to gain widespread adoption in the United States.

The superiority of ESD over EMR has been well established in multiple publications from both Eastern and Western literature. Mejia-Perez et al, in a multicenter cohort study from eight centers in North America, compared outcomes of ESD vs EMR for BE with high-grade dysplasia (HGD) or T1a adenocarcinoma in 243 patients. ESD achieved significantly higher en bloc resection rates (89% vs 43%) and R0 resection rates (73% vs 56%), compared with EMR, along with a substantially lower recurrence/residual disease rate on follow-up (3.5% in the ESD group vs 31.4% in EMR group). Additionally, more patients required repeat endoscopic resection after EMR to treat residual or recurrent disease (EMR, 24.2% vs ESD, 3.5%; P < .001).

Han et al conducted a meta-analysis of 22 studies comparing ESD and EMR for early esophageal neoplasia, including both squamous cell carcinoma (SCC) and BE-associated lesions. ESD was associated with significantly higher curative resection rates than EMR (OR, 9.74; 95% CI, 4.83-19.62; P < .0001). Of note, lesion size was a critical factor in determining the advantage of ESD. For lesions ≤ 10 mm, curative resection rates were comparable between ESD and EMR. However, for lesions > 10 mm, ESD achieved significantly higher curative resection rates. This size-based recommendation has been adopted by the American Society of Gastrointestinal Endoscopy (ASGE) in their recent guidelines on ESD indications for esophageal lesions. ASGE guidelines favors ESD over EMR for SCC lesions > 15 mm and for nodular BE with dysplasia or early EAC > 20 mm.

ESD is particularly beneficial in patients who develop early adenocarcinoma after RFA or EMR. Mesureur et al evaluated the efficacy of salvage ESD for Barrett’s recurrence or residual BE following RFA. In their multicenter retrospective study of 56 patients, salvage ESD achieved an en bloc resection rate of 89.3%, despite significant fibrosis, with an R0 resection rate of 66%. At a median follow-up of 14 months, most patients remained in endoscopic remission without the need for esophagectomy.

Combining ESD with RFA has also been shown to accelerate the eradication of BE with dysplasia while reducing the number of required sessions. Our group demonstrated the high efficacy of ESD followed by RFA in 18 patients, most of whom had long-segment BE with HGD or EAC. On average, patients required only one to two RFA sessions after ESD to achieve complete eradication of intestinal metaplasia (CE-IM). Over a median follow-up of 42.5 months (IQR, 28-59.25), complete eradication of early esophageal cancer was achieved in 13 patients (100%), eradication of dysplasia in 15 patients (100%), and CE-IM in 14 patients (77.8%).

Despite the overwhelming evidence supporting ESD and the strong endorsement from professional societies, adoption in the West continues to lag. Several factors contribute to this gap. First, ESD has a steep learning curve. Our data showed that, on average, an untutored practitioner achieved competency after 150-250 procedures, a finding corroborated by other US groups.

Second, there is no specific CPT code for ESD in the United States. Physicians are forced to bill the procedure as EMR or use an unlisted code, resulting in reimbursement that does not reflect the time and complexity of the procedure. Our group showed that physician reimbursement for ESD is highly variable, ranging from $50 to $800 per case, depending on insurance type.

Third, the increasing emphasis on productivity and RVU generation in academic settings has hindered the growth of ESD training in many institutions. Still, the outlook for ESD in the United States remains encouraging. Multiple industry-sponsored training courses are held annually, and professional societies are investing heavily in expanding access to structured education in ESD. Industry is also innovating devices that improve procedural efficiency and safety. Adopting novel approaches, such as traction-assisted ESD, has made the technique more appealing to endoscopists concerned about long procedure times. For example, our group proposed a standardized esophageal ESD technique that incorporates specimen self-retraction. This method improves both safety and speed and has helped address several procedural challenges. We’ve demonstrated that consistency in technique can substantially expedite esophageal ESD.

Fast forward 5 years: We anticipate a dedicated CPT code for ESD, broader access to advanced resection tools, and an expanding number of fellowships offering structured ESD training. These developments are poised to eliminate many of the current barriers. In summary, with robust data supporting the efficacy of ESD in early esophageal cancer, the focus in the United States should shift toward mastering and integrating the technique, rather than dismissing it in favor of piecemeal EMR.

Dr. Othman is chief of the gastroenterology and hepatology section at Baylor College of Medicine and Medicine Subspecialities Service Line Chief at Baylor St Luke’s Medical Center, both in Houston. He declares no conflicts of interest.

Dear colleagues,

Many of us diagnose and treat patients with Barrett’s esophagus, estimated to affect up to 5.6% of the US adult population. There has been an expanding array of tools to help diagnose and effectively treat Barrett’s esophagus with dysplasia and malignancy. In particular, endoscopic submucosal dissection (ESD) has emerged as an important method for treating early cancer in the gastrointestinal tract.

But how do we incorporate ESD into our algorithm for management, especially with the popularity and effectiveness of endoscopic mucosal resection (EMR)? In this issue of Perspectives we aim to provide context for the use of ESD, as compared with EMR. Dr. Silvio de Melo discusses his preferred EMR technique and its many advantages in the management of BE, including for residual or refractory areas. In contrast, Dr. Mohamed Othman reviews the power of ESD and when we should consider this approach over EMR. We hope these discussions will facilitate your care for patients with Barrett’s esophagus.

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Endoscopic Mucosal Resection: The ‘Workhorse’ for Patient Care

BY SILVIO W. DE MELO JR, MD, AGAF

Barrett’s esophagus (BE) remains an important clinical problem, being one of the modifiable risk factors for esophageal adenocarcinoma. The care for BE is complex and requires several steps to correctly formulate a therapeutic plan. It starts with a proper endoscopic examination. It is recommended to spend at least 1 minute inspecting and evaluating every centimeter of the salmon-colored epithelium, looking for change in vascular pattern, erosions/ulcers, nodules, and/or masses. After the inspection, random biopsies every 1-2 cm plus targeted biopsies will guide you. It is still controversial if the addition of other sampling strategies, such as brushings or confocal endomicroscopy, is needed.

The introduction of radiofrequency ablation (RFA) was paramount in popularizing the treatment options for BE and sunsetting the previous dominant modality, photodynamic therapy (PDT). RFA proved to have a superior clinical efficacy in replacing the intestinal metaplasia/BE with neosquamous epithelium while boosting a much better safety profile, compared with PDT. However, RFA is most efficacious for “flat BE” and it is not an effective, nor recommended, method to treat nodular BE or early cancer, such as carcinoma in situ or nodular high-grade dysplasia. Endoscopic mucosal resection (EMR) is utilized to overcome those limitations.

There are several techniques utilized for EMR:

• The lift and snare technique.
• The snare-in-cap technique.
• The Band-snare technique.

The free-hand submucosal lift and snare is not frequently used in the esophagus. It is difficult to maintain visualization while being confident that one has the whole lesion inside the snare and that the distal (anal side) part of the lesion is free of any unwanted tissue (to minimize complications such as perforations or unwelcomed gastric resections). It is difficult after the first resection to lift an adjacent area, as the fluid easily leaks from the first resected spot, thus removing larger lesions in piece-meal fashion is challenging. This technique can be used in small (in my personal experience, less than 5 mm) lesions, but, given that there are better and safer alternatives, I almost never use this technique for my esophageal EMR cases. I prefer to use the band-snare technique even for lesions under 5 mm.

The snare-in-cap technique has been utilized in the esophagus. In this technique, a cap is attached to the distal end of the scope and the size of the resection is determined by the size of the cap, usually under 1.5 cm. Because of the risk of perforation without previous lifting, it is required that the lesion is lifted with a submucosal fluid, saline or any Food and Drug Administration–approved EMR solution. The lesion is then suctioned inside the cap where the snare had been previously opened inside the cap, the snare is closed, and the tissue is resected. The same limitations regarding the inability to remove larger lesions (greater than 1.5 cm) because of the challenge in lifting the adjacent area applies here. However, the perforation risk for this technique is higher than the traditional lift and the band and snare techniques. Thus, this technique has fallen out of favor for most endoscopists.

The third technique (band-snare EMR) is the one that most endoscopists use for endoscopic mucosal resection. It is a small variation of the already time-tested and very familiar procedure of esophageal variceal band ligation (EVL). There are multiple commercially available kits for esophageal EMR. The kit contains the chamber with the bands and a proprietary hexagonal snare used to resect the specimen.

The advantages of this technique are:

• It is widely commercially available.
• It builds on a familiar procedure, EVL, therefore the learning curve is short.
• The set-up is quick and the procedure can be completed safely and effectively.
• There is no need for injecting the submucosal with a lifting solution.
• Despite the band having a size limitation of 1 cm, one can remove larger lesions by repeating the band and resect process, using the rosette technique.

Band-snare EMR also has limitations:

• There are only six bands on each chamber. Depending on the size of the lesion, one may need to use multiple kits.
• It is not suitable for en bloc resection of lesions greater than 1 cm.

My experience with band EMR is that we can complete the procedure in under 1 hour. The dreaded complication of perforation occurs in under 1% of cases, most bleeding episodes can easily be controlled endoscopically, and the risk of post-EMR stricture is minimal. Therefore, band EMR is the most used technique for esophageal endoscopic resections.

Esophageal EMR is also effective for other indications in BE therapy, such as residual and recurrent BE. Band-snare EMR can be used for an en bloc resection or rosette technique for the areas resistant to ablation therapies with great success and safety.

From a financial standpoint, comparing EMR with endoscopic submucosal dissection (ESD), EMR is the superior strategy given that EMR is widely available, has a much shorter learning curve, has a greater safety profile, is applicable to a wider variety of indications, and has a more favorable return on investment. EMR should be the workhorse for the care of patients with BE, reserving ESD for specific indications.

In summary, there is no “one-size-fits-all” endoscopic therapy in the care of BE. Most Barrett’s patients can be successfully treated with a combination of ablation plus EMR, reserving ESD for select cases.

Dr. de Melo is section chief of gastroenterology at the Orlando VA Healthcare System, Orlando, Florida. He declares no conflicts of interest.

ESD Over EMR for Resecting Esophageal Lesions

BY MOHAMED O. OTHMAN, MD, AGAF

Although endoscopic submucosal dissection (ESD) is the preferred endoscopic resection method in the East, the adoption of this technique in the West, particularly in the United States, has faced many hurdles. Many endoscopists who routinely perform piecemeal endoscopic mucosal resection (EMR) question the utility of ESD, arguing that EMR is just as effective. While this may hold true in certain situations, the global trend in the endoscopic treatment of early esophageal squamous cell carcinoma, nodular Barrett’s esophagus (BE), and early esophageal adenocarcinoma (EAC) has clearly shifted toward ESD. In this perspective, I will summarize why ESD is preferred over EMR for these indications and explore why ESD has yet to gain widespread adoption in the United States.

The superiority of ESD over EMR has been well established in multiple publications from both Eastern and Western literature. Mejia-Perez et al, in a multicenter cohort study from eight centers in North America, compared outcomes of ESD vs EMR for BE with high-grade dysplasia (HGD) or T1a adenocarcinoma in 243 patients. ESD achieved significantly higher en bloc resection rates (89% vs 43%) and R0 resection rates (73% vs 56%), compared with EMR, along with a substantially lower recurrence/residual disease rate on follow-up (3.5% in the ESD group vs 31.4% in EMR group). Additionally, more patients required repeat endoscopic resection after EMR to treat residual or recurrent disease (EMR, 24.2% vs ESD, 3.5%; P < .001).

Han et al conducted a meta-analysis of 22 studies comparing ESD and EMR for early esophageal neoplasia, including both squamous cell carcinoma (SCC) and BE-associated lesions. ESD was associated with significantly higher curative resection rates than EMR (OR, 9.74; 95% CI, 4.83-19.62; P < .0001). Of note, lesion size was a critical factor in determining the advantage of ESD. For lesions ≤ 10 mm, curative resection rates were comparable between ESD and EMR. However, for lesions > 10 mm, ESD achieved significantly higher curative resection rates. This size-based recommendation has been adopted by the American Society of Gastrointestinal Endoscopy (ASGE) in their recent guidelines on ESD indications for esophageal lesions. ASGE guidelines favors ESD over EMR for SCC lesions > 15 mm and for nodular BE with dysplasia or early EAC > 20 mm.

ESD is particularly beneficial in patients who develop early adenocarcinoma after RFA or EMR. Mesureur et al evaluated the efficacy of salvage ESD for Barrett’s recurrence or residual BE following RFA. In their multicenter retrospective study of 56 patients, salvage ESD achieved an en bloc resection rate of 89.3%, despite significant fibrosis, with an R0 resection rate of 66%. At a median follow-up of 14 months, most patients remained in endoscopic remission without the need for esophagectomy.

Combining ESD with RFA has also been shown to accelerate the eradication of BE with dysplasia while reducing the number of required sessions. Our group demonstrated the high efficacy of ESD followed by RFA in 18 patients, most of whom had long-segment BE with HGD or EAC. On average, patients required only one to two RFA sessions after ESD to achieve complete eradication of intestinal metaplasia (CE-IM). Over a median follow-up of 42.5 months (IQR, 28-59.25), complete eradication of early esophageal cancer was achieved in 13 patients (100%), eradication of dysplasia in 15 patients (100%), and CE-IM in 14 patients (77.8%).

Despite the overwhelming evidence supporting ESD and the strong endorsement from professional societies, adoption in the West continues to lag. Several factors contribute to this gap. First, ESD has a steep learning curve. Our data showed that, on average, an untutored practitioner achieved competency after 150-250 procedures, a finding corroborated by other US groups.

Second, there is no specific CPT code for ESD in the United States. Physicians are forced to bill the procedure as EMR or use an unlisted code, resulting in reimbursement that does not reflect the time and complexity of the procedure. Our group showed that physician reimbursement for ESD is highly variable, ranging from $50 to $800 per case, depending on insurance type.

Third, the increasing emphasis on productivity and RVU generation in academic settings has hindered the growth of ESD training in many institutions. Still, the outlook for ESD in the United States remains encouraging. Multiple industry-sponsored training courses are held annually, and professional societies are investing heavily in expanding access to structured education in ESD. Industry is also innovating devices that improve procedural efficiency and safety. Adopting novel approaches, such as traction-assisted ESD, has made the technique more appealing to endoscopists concerned about long procedure times. For example, our group proposed a standardized esophageal ESD technique that incorporates specimen self-retraction. This method improves both safety and speed and has helped address several procedural challenges. We’ve demonstrated that consistency in technique can substantially expedite esophageal ESD.

Fast forward 5 years: We anticipate a dedicated CPT code for ESD, broader access to advanced resection tools, and an expanding number of fellowships offering structured ESD training. These developments are poised to eliminate many of the current barriers. In summary, with robust data supporting the efficacy of ESD in early esophageal cancer, the focus in the United States should shift toward mastering and integrating the technique, rather than dismissing it in favor of piecemeal EMR.

Dr. Othman is chief of the gastroenterology and hepatology section at Baylor College of Medicine and Medicine Subspecialities Service Line Chief at Baylor St Luke’s Medical Center, both in Houston. He declares no conflicts of interest.

Dear colleagues,

Many of us diagnose and treat patients with Barrett’s esophagus, estimated to affect up to 5.6% of the US adult population. There has been an expanding array of tools to help diagnose and effectively treat Barrett’s esophagus with dysplasia and malignancy. In particular, endoscopic submucosal dissection (ESD) has emerged as an important method for treating early cancer in the gastrointestinal tract.

But how do we incorporate ESD into our algorithm for management, especially with the popularity and effectiveness of endoscopic mucosal resection (EMR)? In this issue of Perspectives we aim to provide context for the use of ESD, as compared with EMR. Dr. Silvio de Melo discusses his preferred EMR technique and its many advantages in the management of BE, including for residual or refractory areas. In contrast, Dr. Mohamed Othman reviews the power of ESD and when we should consider this approach over EMR. We hope these discussions will facilitate your care for patients with Barrett’s esophagus.

We also welcome your thoughts on this topic — join the conversation on X at @AGA_GIHN. 

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, and chief of endoscopy at West Haven VA Medical Center, both in Connecticut. He is an associate editor for GI & Hepatology News.

Endoscopic Mucosal Resection: The ‘Workhorse’ for Patient Care

BY SILVIO W. DE MELO JR, MD, AGAF

Barrett’s esophagus (BE) remains an important clinical problem, being one of the modifiable risk factors for esophageal adenocarcinoma. The care for BE is complex and requires several steps to correctly formulate a therapeutic plan. It starts with a proper endoscopic examination. It is recommended to spend at least 1 minute inspecting and evaluating every centimeter of the salmon-colored epithelium, looking for change in vascular pattern, erosions/ulcers, nodules, and/or masses. After the inspection, random biopsies every 1-2 cm plus targeted biopsies will guide you. It is still controversial if the addition of other sampling strategies, such as brushings or confocal endomicroscopy, is needed.

The introduction of radiofrequency ablation (RFA) was paramount in popularizing the treatment options for BE and sunsetting the previous dominant modality, photodynamic therapy (PDT). RFA proved to have a superior clinical efficacy in replacing the intestinal metaplasia/BE with neosquamous epithelium while boosting a much better safety profile, compared with PDT. However, RFA is most efficacious for “flat BE” and it is not an effective, nor recommended, method to treat nodular BE or early cancer, such as carcinoma in situ or nodular high-grade dysplasia. Endoscopic mucosal resection (EMR) is utilized to overcome those limitations.

There are several techniques utilized for EMR:

• The lift and snare technique.
• The snare-in-cap technique.
• The Band-snare technique.

The free-hand submucosal lift and snare is not frequently used in the esophagus. It is difficult to maintain visualization while being confident that one has the whole lesion inside the snare and that the distal (anal side) part of the lesion is free of any unwanted tissue (to minimize complications such as perforations or unwelcomed gastric resections). It is difficult after the first resection to lift an adjacent area, as the fluid easily leaks from the first resected spot, thus removing larger lesions in piece-meal fashion is challenging. This technique can be used in small (in my personal experience, less than 5 mm) lesions, but, given that there are better and safer alternatives, I almost never use this technique for my esophageal EMR cases. I prefer to use the band-snare technique even for lesions under 5 mm.

The snare-in-cap technique has been utilized in the esophagus. In this technique, a cap is attached to the distal end of the scope and the size of the resection is determined by the size of the cap, usually under 1.5 cm. Because of the risk of perforation without previous lifting, it is required that the lesion is lifted with a submucosal fluid, saline or any Food and Drug Administration–approved EMR solution. The lesion is then suctioned inside the cap where the snare had been previously opened inside the cap, the snare is closed, and the tissue is resected. The same limitations regarding the inability to remove larger lesions (greater than 1.5 cm) because of the challenge in lifting the adjacent area applies here. However, the perforation risk for this technique is higher than the traditional lift and the band and snare techniques. Thus, this technique has fallen out of favor for most endoscopists.

The third technique (band-snare EMR) is the one that most endoscopists use for endoscopic mucosal resection. It is a small variation of the already time-tested and very familiar procedure of esophageal variceal band ligation (EVL). There are multiple commercially available kits for esophageal EMR. The kit contains the chamber with the bands and a proprietary hexagonal snare used to resect the specimen.

The advantages of this technique are:

• It is widely commercially available.
• It builds on a familiar procedure, EVL, therefore the learning curve is short.
• The set-up is quick and the procedure can be completed safely and effectively.
• There is no need for injecting the submucosal with a lifting solution.
• Despite the band having a size limitation of 1 cm, one can remove larger lesions by repeating the band and resect process, using the rosette technique.

Band-snare EMR also has limitations:

• There are only six bands on each chamber. Depending on the size of the lesion, one may need to use multiple kits.
• It is not suitable for en bloc resection of lesions greater than 1 cm.

My experience with band EMR is that we can complete the procedure in under 1 hour. The dreaded complication of perforation occurs in under 1% of cases, most bleeding episodes can easily be controlled endoscopically, and the risk of post-EMR stricture is minimal. Therefore, band EMR is the most used technique for esophageal endoscopic resections.

Esophageal EMR is also effective for other indications in BE therapy, such as residual and recurrent BE. Band-snare EMR can be used for an en bloc resection or rosette technique for the areas resistant to ablation therapies with great success and safety.

From a financial standpoint, comparing EMR with endoscopic submucosal dissection (ESD), EMR is the superior strategy given that EMR is widely available, has a much shorter learning curve, has a greater safety profile, is applicable to a wider variety of indications, and has a more favorable return on investment. EMR should be the workhorse for the care of patients with BE, reserving ESD for specific indications.

In summary, there is no “one-size-fits-all” endoscopic therapy in the care of BE. Most Barrett’s patients can be successfully treated with a combination of ablation plus EMR, reserving ESD for select cases.

Dr. de Melo is section chief of gastroenterology at the Orlando VA Healthcare System, Orlando, Florida. He declares no conflicts of interest.

ESD Over EMR for Resecting Esophageal Lesions

BY MOHAMED O. OTHMAN, MD, AGAF

Although endoscopic submucosal dissection (ESD) is the preferred endoscopic resection method in the East, the adoption of this technique in the West, particularly in the United States, has faced many hurdles. Many endoscopists who routinely perform piecemeal endoscopic mucosal resection (EMR) question the utility of ESD, arguing that EMR is just as effective. While this may hold true in certain situations, the global trend in the endoscopic treatment of early esophageal squamous cell carcinoma, nodular Barrett’s esophagus (BE), and early esophageal adenocarcinoma (EAC) has clearly shifted toward ESD. In this perspective, I will summarize why ESD is preferred over EMR for these indications and explore why ESD has yet to gain widespread adoption in the United States.

The superiority of ESD over EMR has been well established in multiple publications from both Eastern and Western literature. Mejia-Perez et al, in a multicenter cohort study from eight centers in North America, compared outcomes of ESD vs EMR for BE with high-grade dysplasia (HGD) or T1a adenocarcinoma in 243 patients. ESD achieved significantly higher en bloc resection rates (89% vs 43%) and R0 resection rates (73% vs 56%), compared with EMR, along with a substantially lower recurrence/residual disease rate on follow-up (3.5% in the ESD group vs 31.4% in EMR group). Additionally, more patients required repeat endoscopic resection after EMR to treat residual or recurrent disease (EMR, 24.2% vs ESD, 3.5%; P < .001).

Han et al conducted a meta-analysis of 22 studies comparing ESD and EMR for early esophageal neoplasia, including both squamous cell carcinoma (SCC) and BE-associated lesions. ESD was associated with significantly higher curative resection rates than EMR (OR, 9.74; 95% CI, 4.83-19.62; P < .0001). Of note, lesion size was a critical factor in determining the advantage of ESD. For lesions ≤ 10 mm, curative resection rates were comparable between ESD and EMR. However, for lesions > 10 mm, ESD achieved significantly higher curative resection rates. This size-based recommendation has been adopted by the American Society of Gastrointestinal Endoscopy (ASGE) in their recent guidelines on ESD indications for esophageal lesions. ASGE guidelines favors ESD over EMR for SCC lesions > 15 mm and for nodular BE with dysplasia or early EAC > 20 mm.

ESD is particularly beneficial in patients who develop early adenocarcinoma after RFA or EMR. Mesureur et al evaluated the efficacy of salvage ESD for Barrett’s recurrence or residual BE following RFA. In their multicenter retrospective study of 56 patients, salvage ESD achieved an en bloc resection rate of 89.3%, despite significant fibrosis, with an R0 resection rate of 66%. At a median follow-up of 14 months, most patients remained in endoscopic remission without the need for esophagectomy.

Combining ESD with RFA has also been shown to accelerate the eradication of BE with dysplasia while reducing the number of required sessions. Our group demonstrated the high efficacy of ESD followed by RFA in 18 patients, most of whom had long-segment BE with HGD or EAC. On average, patients required only one to two RFA sessions after ESD to achieve complete eradication of intestinal metaplasia (CE-IM). Over a median follow-up of 42.5 months (IQR, 28-59.25), complete eradication of early esophageal cancer was achieved in 13 patients (100%), eradication of dysplasia in 15 patients (100%), and CE-IM in 14 patients (77.8%).

Despite the overwhelming evidence supporting ESD and the strong endorsement from professional societies, adoption in the West continues to lag. Several factors contribute to this gap. First, ESD has a steep learning curve. Our data showed that, on average, an untutored practitioner achieved competency after 150-250 procedures, a finding corroborated by other US groups.

Second, there is no specific CPT code for ESD in the United States. Physicians are forced to bill the procedure as EMR or use an unlisted code, resulting in reimbursement that does not reflect the time and complexity of the procedure. Our group showed that physician reimbursement for ESD is highly variable, ranging from $50 to $800 per case, depending on insurance type.

Third, the increasing emphasis on productivity and RVU generation in academic settings has hindered the growth of ESD training in many institutions. Still, the outlook for ESD in the United States remains encouraging. Multiple industry-sponsored training courses are held annually, and professional societies are investing heavily in expanding access to structured education in ESD. Industry is also innovating devices that improve procedural efficiency and safety. Adopting novel approaches, such as traction-assisted ESD, has made the technique more appealing to endoscopists concerned about long procedure times. For example, our group proposed a standardized esophageal ESD technique that incorporates specimen self-retraction. This method improves both safety and speed and has helped address several procedural challenges. We’ve demonstrated that consistency in technique can substantially expedite esophageal ESD.

Fast forward 5 years: We anticipate a dedicated CPT code for ESD, broader access to advanced resection tools, and an expanding number of fellowships offering structured ESD training. These developments are poised to eliminate many of the current barriers. In summary, with robust data supporting the efficacy of ESD in early esophageal cancer, the focus in the United States should shift toward mastering and integrating the technique, rather than dismissing it in favor of piecemeal EMR.

Dr. Othman is chief of the gastroenterology and hepatology section at Baylor College of Medicine and Medicine Subspecialities Service Line Chief at Baylor St Luke’s Medical Center, both in Houston. He declares no conflicts of interest.

In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper.

Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant listing in young adults aged 18-40 years, said corresponding author Jennifer A. Panganiban, MD, Children’s Hospital of Philadelphia, Philadelphia.

The paper, published in Obesity Pillars, represents “a call to action that has been long overdue,” Panganiban told GI & Hepatology News.

The goal of the authors was to bring global awareness to the recent changes in the pediatric MASLD landscape — especially in medication use — and to empower clinicians treating the disease, she explained.

The recommendations are based on a combination of the latest published evidence and clinical expertise from eight hepatologists/gastroenterologists and two physicians from the Obesity Medicine Association, Centennial, Colorado.

One of the major barriers to MASLD management in children is suboptimal screening resulting in underdiagnosis, said Panganiban. “Unfortunately, only up to 30% of children are being screened in their pediatrician’s office.”

The new guideline outlines the patient care process from screening, referral to a subspecialist, and workup; however, the primary focus is on treatment with medication options that were previously not available or underutilized, she said.

 

Successful and Sustainable Weight Loss

Adiposity and weight gain make MASLD worse, but weight reduction has been shown to improve the condition, the authors noted. Previous strategies for curbing MASLD in children with obesity have focused mainly on lifestyle changes, but with limited success.

Nevertheless, the authors recommend continuing physical activity and nutrition as treatments for MASLD in children, with a plan tailored specifically to the patient.

In addition, however, they suggest that anti-obesity medications started early in the disease may help reduce costs and improve future outcomes.

Although glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have not yet been studied specifically for pediatric MASLD, data from studies of pediatric obesity, diabetes, and other retrospective studies are encouraging, the authors wrote.

The GLP-1 RAs liraglutide and semaglutide are both approved by the US Food and Drug Administration (FDA) for managing obesity in children and adolescents aged 12 years or older, they noted. And a recent phase 3a randomized trial showed that liraglutide, not yet approved for children younger than 12 years, led to a mean change in body mass index of 5.8% from baseline to 56 weeks in children aged 6-11 years with obesity.

GLP-1 RAs not only are effective for weight management but also improve other metabolic dysfunction indicators including cholesterol and blood pressure, which makes these medications an even more beneficial option for individuals with obesity and MASLD, Panganiban and colleagues wrote.

For example, a recent single-center study of 111 children with MASLD (mean age, 15 years) showed a significant improvement in alanine aminotransferase levels with the use of GLP-1 RAs, although body mass index and weight were unchanged.

Regaining weight after discontinuing GLP-1 RAs is the main barrier to their use for MASLD, the authors noted. In addition, GLP-1 RAs are contraindicated in some situations, such as in those with a history of serious hypersensitivity, and in patients with a personal or family history of either medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 based on animal studies showing an association with the medications and thyroid C–cell tumors.

Other FDA-approved medication options for obesity in children include metformin, topiramate, and phentermine, as well as bupropion, lisdexamfetamine, and setmelanotide, the authors said.

Resmetirom, a thyroid hormone receptor-beta agonist, which is another significant breakthrough in MASLD for adults, has not yet been tested or approved for pediatric use.

In addition to medications, metabolic bariatric surgery has shown effectiveness in children with obesity and/or MASLD by reducing liver fat and reversing fibrosis, as shown in the Teen-LABS study, the authors wrote. However, long-term data on fibrosis reversal are limited, and cost and access remain barriers.

 

More Research Needed

The joint expert review is intended as an educational tool that may require updates and should not be interpreted as rules for individual patient care, the authors cautioned. And physical activity and nutrition remain the primary treatment of MASLD and should be continued in conjunction with other treatment modalities, they emphasized.

Looking ahead, research is needed to develop accurate and reliable noninvasive biomarkers to diagnose and assess obesity treatment efficacy, Panganiban told GI & Hepatology News.

Also needed are multicenter randomized control trials in children with obesity involving different medications that have been successful in the treatment of metabolic dysfunction–associated steatohepatitis/fibrosis in adults, such as GLP-1 RAs or resmetirom, she added.

 

Educating Clinicians on Early Identification

When obesity occurs in childhood, it starts a process of additional complications that arise in earlier ages in adults, said Saul J. Karpen, MD, chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, in an interview.“Given the epidemic of obesity, altered diets, and reduced physical activities during younger ages, it is not easy to identify which children are at greater risk of MASLD,” said Karpen.

“It requires insight from the care providers and often imaging, a blood test, or a referral to a pediatric hepatologist, and not every region has easy access to such expertise,” Karpen said.

The new review is important because it highlights the fact that obesity and its consequences are not limited to adulthood, and that educated clinicians are in a position to get an early start on treatment in children, Karpen noted.

The guideline received no outside funding. Panganiban and Karpen had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper.

Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant listing in young adults aged 18-40 years, said corresponding author Jennifer A. Panganiban, MD, Children’s Hospital of Philadelphia, Philadelphia.

The paper, published in Obesity Pillars, represents “a call to action that has been long overdue,” Panganiban told GI & Hepatology News.

The goal of the authors was to bring global awareness to the recent changes in the pediatric MASLD landscape — especially in medication use — and to empower clinicians treating the disease, she explained.

The recommendations are based on a combination of the latest published evidence and clinical expertise from eight hepatologists/gastroenterologists and two physicians from the Obesity Medicine Association, Centennial, Colorado.

One of the major barriers to MASLD management in children is suboptimal screening resulting in underdiagnosis, said Panganiban. “Unfortunately, only up to 30% of children are being screened in their pediatrician’s office.”

The new guideline outlines the patient care process from screening, referral to a subspecialist, and workup; however, the primary focus is on treatment with medication options that were previously not available or underutilized, she said.

 

Successful and Sustainable Weight Loss

Adiposity and weight gain make MASLD worse, but weight reduction has been shown to improve the condition, the authors noted. Previous strategies for curbing MASLD in children with obesity have focused mainly on lifestyle changes, but with limited success.

Nevertheless, the authors recommend continuing physical activity and nutrition as treatments for MASLD in children, with a plan tailored specifically to the patient.

In addition, however, they suggest that anti-obesity medications started early in the disease may help reduce costs and improve future outcomes.

Although glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have not yet been studied specifically for pediatric MASLD, data from studies of pediatric obesity, diabetes, and other retrospective studies are encouraging, the authors wrote.

The GLP-1 RAs liraglutide and semaglutide are both approved by the US Food and Drug Administration (FDA) for managing obesity in children and adolescents aged 12 years or older, they noted. And a recent phase 3a randomized trial showed that liraglutide, not yet approved for children younger than 12 years, led to a mean change in body mass index of 5.8% from baseline to 56 weeks in children aged 6-11 years with obesity.

GLP-1 RAs not only are effective for weight management but also improve other metabolic dysfunction indicators including cholesterol and blood pressure, which makes these medications an even more beneficial option for individuals with obesity and MASLD, Panganiban and colleagues wrote.

For example, a recent single-center study of 111 children with MASLD (mean age, 15 years) showed a significant improvement in alanine aminotransferase levels with the use of GLP-1 RAs, although body mass index and weight were unchanged.

Regaining weight after discontinuing GLP-1 RAs is the main barrier to their use for MASLD, the authors noted. In addition, GLP-1 RAs are contraindicated in some situations, such as in those with a history of serious hypersensitivity, and in patients with a personal or family history of either medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 based on animal studies showing an association with the medications and thyroid C–cell tumors.

Other FDA-approved medication options for obesity in children include metformin, topiramate, and phentermine, as well as bupropion, lisdexamfetamine, and setmelanotide, the authors said.

Resmetirom, a thyroid hormone receptor-beta agonist, which is another significant breakthrough in MASLD for adults, has not yet been tested or approved for pediatric use.

In addition to medications, metabolic bariatric surgery has shown effectiveness in children with obesity and/or MASLD by reducing liver fat and reversing fibrosis, as shown in the Teen-LABS study, the authors wrote. However, long-term data on fibrosis reversal are limited, and cost and access remain barriers.

 

More Research Needed

The joint expert review is intended as an educational tool that may require updates and should not be interpreted as rules for individual patient care, the authors cautioned. And physical activity and nutrition remain the primary treatment of MASLD and should be continued in conjunction with other treatment modalities, they emphasized.

Looking ahead, research is needed to develop accurate and reliable noninvasive biomarkers to diagnose and assess obesity treatment efficacy, Panganiban told GI & Hepatology News.

Also needed are multicenter randomized control trials in children with obesity involving different medications that have been successful in the treatment of metabolic dysfunction–associated steatohepatitis/fibrosis in adults, such as GLP-1 RAs or resmetirom, she added.

 

Educating Clinicians on Early Identification

When obesity occurs in childhood, it starts a process of additional complications that arise in earlier ages in adults, said Saul J. Karpen, MD, chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, in an interview.“Given the epidemic of obesity, altered diets, and reduced physical activities during younger ages, it is not easy to identify which children are at greater risk of MASLD,” said Karpen.

“It requires insight from the care providers and often imaging, a blood test, or a referral to a pediatric hepatologist, and not every region has easy access to such expertise,” Karpen said.

The new review is important because it highlights the fact that obesity and its consequences are not limited to adulthood, and that educated clinicians are in a position to get an early start on treatment in children, Karpen noted.

The guideline received no outside funding. Panganiban and Karpen had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper.

Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant listing in young adults aged 18-40 years, said corresponding author Jennifer A. Panganiban, MD, Children’s Hospital of Philadelphia, Philadelphia.

The paper, published in Obesity Pillars, represents “a call to action that has been long overdue,” Panganiban told GI & Hepatology News.

The goal of the authors was to bring global awareness to the recent changes in the pediatric MASLD landscape — especially in medication use — and to empower clinicians treating the disease, she explained.

The recommendations are based on a combination of the latest published evidence and clinical expertise from eight hepatologists/gastroenterologists and two physicians from the Obesity Medicine Association, Centennial, Colorado.

One of the major barriers to MASLD management in children is suboptimal screening resulting in underdiagnosis, said Panganiban. “Unfortunately, only up to 30% of children are being screened in their pediatrician’s office.”

The new guideline outlines the patient care process from screening, referral to a subspecialist, and workup; however, the primary focus is on treatment with medication options that were previously not available or underutilized, she said.

 

Successful and Sustainable Weight Loss

Adiposity and weight gain make MASLD worse, but weight reduction has been shown to improve the condition, the authors noted. Previous strategies for curbing MASLD in children with obesity have focused mainly on lifestyle changes, but with limited success.

Nevertheless, the authors recommend continuing physical activity and nutrition as treatments for MASLD in children, with a plan tailored specifically to the patient.

In addition, however, they suggest that anti-obesity medications started early in the disease may help reduce costs and improve future outcomes.

Although glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have not yet been studied specifically for pediatric MASLD, data from studies of pediatric obesity, diabetes, and other retrospective studies are encouraging, the authors wrote.

The GLP-1 RAs liraglutide and semaglutide are both approved by the US Food and Drug Administration (FDA) for managing obesity in children and adolescents aged 12 years or older, they noted. And a recent phase 3a randomized trial showed that liraglutide, not yet approved for children younger than 12 years, led to a mean change in body mass index of 5.8% from baseline to 56 weeks in children aged 6-11 years with obesity.

GLP-1 RAs not only are effective for weight management but also improve other metabolic dysfunction indicators including cholesterol and blood pressure, which makes these medications an even more beneficial option for individuals with obesity and MASLD, Panganiban and colleagues wrote.

For example, a recent single-center study of 111 children with MASLD (mean age, 15 years) showed a significant improvement in alanine aminotransferase levels with the use of GLP-1 RAs, although body mass index and weight were unchanged.

Regaining weight after discontinuing GLP-1 RAs is the main barrier to their use for MASLD, the authors noted. In addition, GLP-1 RAs are contraindicated in some situations, such as in those with a history of serious hypersensitivity, and in patients with a personal or family history of either medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 based on animal studies showing an association with the medications and thyroid C–cell tumors.

Other FDA-approved medication options for obesity in children include metformin, topiramate, and phentermine, as well as bupropion, lisdexamfetamine, and setmelanotide, the authors said.

Resmetirom, a thyroid hormone receptor-beta agonist, which is another significant breakthrough in MASLD for adults, has not yet been tested or approved for pediatric use.

In addition to medications, metabolic bariatric surgery has shown effectiveness in children with obesity and/or MASLD by reducing liver fat and reversing fibrosis, as shown in the Teen-LABS study, the authors wrote. However, long-term data on fibrosis reversal are limited, and cost and access remain barriers.

 

More Research Needed

The joint expert review is intended as an educational tool that may require updates and should not be interpreted as rules for individual patient care, the authors cautioned. And physical activity and nutrition remain the primary treatment of MASLD and should be continued in conjunction with other treatment modalities, they emphasized.

Looking ahead, research is needed to develop accurate and reliable noninvasive biomarkers to diagnose and assess obesity treatment efficacy, Panganiban told GI & Hepatology News.

Also needed are multicenter randomized control trials in children with obesity involving different medications that have been successful in the treatment of metabolic dysfunction–associated steatohepatitis/fibrosis in adults, such as GLP-1 RAs or resmetirom, she added.

 

Educating Clinicians on Early Identification

When obesity occurs in childhood, it starts a process of additional complications that arise in earlier ages in adults, said Saul J. Karpen, MD, chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, in an interview.“Given the epidemic of obesity, altered diets, and reduced physical activities during younger ages, it is not easy to identify which children are at greater risk of MASLD,” said Karpen.

“It requires insight from the care providers and often imaging, a blood test, or a referral to a pediatric hepatologist, and not every region has easy access to such expertise,” Karpen said.

The new review is important because it highlights the fact that obesity and its consequences are not limited to adulthood, and that educated clinicians are in a position to get an early start on treatment in children, Karpen noted.

The guideline received no outside funding. Panganiban and Karpen had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.