From the AGA Journals

Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.

These findings suggest that the flagellin cytometric bead array used in the present study could serve as a simple diagnostic and prognostic tool for patients with CD, and point to a new therapeutic target, lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.

Qing Zhao

Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.

“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.

To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.

Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.

This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.

Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.

“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”

Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.

Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.

These findings suggest that the flagellin cytometric bead array used in the present study could serve as a simple diagnostic and prognostic tool for patients with CD, and point to a new therapeutic target, lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.

Qing Zhao

Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.

“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.

To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.

Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.

This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.

Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.

“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”

Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.

Many patients with Crohn’s disease (CD) have a heightened immune response to flagellins expressed by commensal gut bacteria Lachnospiraceae, with seroreactivity appearing up to 5 years prior to development of Crohn’s complications, according to investigators.

These findings suggest that the flagellin cytometric bead array used in the present study could serve as a simple diagnostic and prognostic tool for patients with CD, and point to a new therapeutic target, lead author Qing Zhao, MD, PhD, of the University of Alabama at Birmingham, and colleagues reported.

Qing Zhao

Previously, Zhao and colleagues found that about 30% of patients with CD had elevated IgG responses to multiple Lachnospiraceae flagellins, and stronger reactivity was associated with higher flagellin-specific CD4+ T cells in circulation.

“In this study, we aimed to identify immunodominant B cell peptide epitopes shared among Lachnospiraceae bacterial flagellins in patients with CD and to correlate this immune reactivity with the clinical disease course,” the investigators wrote in Gastroenterology.

To this end, the investigators analyzed serum samples from adult CD patients, pediatric CD patients, and healthy infants without inflammatory bowel disease, with data derived from multiple sources. Adult patients with CD were part of a regional cohort recruited at the University of Alabama at Birmingham, while pediatric patients with CD came from the RISK Stratification Study, a multisite cohort study across the United States and Canada. Samples from healthy infants were collected from three diverse geographic locations: Uganda, Sweden, and the United States, providing a broad comparison of immune responses to Lachnospiraceae flagellin across populations.

Samples were analyzed via two main methods: a flagellin peptide microarray and a cytometric bead array. The microarray, comprising sequential Lachnospiraceae-derived peptides, enabled identification of IgG responses specific to individual bacterial peptides. The cytometric bead array allowed for multiplexed detection of IgG, IgA, and IgM antibodies to these peptides, quantifying immune reactivity and enabling correlation with clinical disease data.

This approach revealed that nearly half of patients with CD — both adults and children — had a strong IgG immune response targeting a specific bacterial peptide in the Lachnospiraceae flagellin hinge region. This response was linked to an increased risk of disease complications over time, suggesting the peptide’s potential as a biomarker for CD severity and progression, according to the investigators.

Of note, healthy infants also exhibited an elevated IgG response to the same bacterial peptide at around 1 year of age, but this response declined as they grew older, in contrast to its persistence in CD patients. This difference points to a possible failure in immune tolerance in CD, where the natural immune response to gut bacteria in infancy may become dysregulated, Zhao and colleagues explained.

“The flagellin cytometric bead array used in this study holds potential for a simplified yet robust diagnostic and prognostic assay for Crohn’s disease,” they concluded. “Given that reactivity to the dominant flagellin epitope is strongly associated with the development of disease complications, this technique may also assist in identifying patients with Crohn’s disease who would benefit from early therapy.”

Zhao and colleagues also called for future studies to characterize the role of flagellin hinge peptide–specific IgG antibodies in CD pathogenesis, and to explore the hinge peptide as a potential therapeutic target.The study was supported by a Synergy Award from the Kenneth Rainin Foundation, a Career Development Award from the Crohn’s and Colitis Foundation, and grants from the Department of Veterans Affairs, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institute of Diabetes and Digestive and Kidney Diseases. One coauthor and the University of Alabama at Birmingham hold a patent on Lachnospiraceae A4 Fla2, licensed for clinical application by Prometheus Laboratories. Four study coauthors have filed a patent for the flagellin peptide cytometric bead array. One coauthor serves as the founder and chief scientific officer of ImmPrev Bio, a company developing an antigen-directed immunotherapy for Crohn’s disease.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

Semaglutide use is associated with an increased risk of retained solid gastric contents, but colonoscopy prep appears to mitigate this issue, according to investigators.

These findings suggest that patients taking GLP-1 receptor agonists (GLP-1RAs) may benefit from a 24-hour liquid fast before anesthetic procedures without the need for a medication hold, reported lead author Haarika Korlipara, MD, of NewYork–Presbyterian/Weill Cornell Medical Center, New York, and colleagues.

“[T]he effects of delayed gastric emptying in patients on long-acting GLP-1RAs are clinically important in the management of anesthetized patients, who may develop periprocedural complications in the setting of retained solid gastric contents,” the investigators wrote in Techniques and Innovations in Gastrointestinal Endoscopy.

NewYork-Presbyterian/Weill Cornell Medical Center

The researchers retrospectively analyzed clinical data from 1,212 patients undergoing upper endoscopy at a tertiary care center. Among them, 602 were on semaglutide for more than four weeks, while 610 were controls not taking the medication.

The primary outcome was the presence of retained solid gastric contents. Secondary outcomes included the need for intubation, early procedure termination, and recommendations for repeat endoscopy.

Semaglutide use was an independent predictor of retained solid gastric contents (odds ratio [OR], 4.74; 95% CI, 2.40-9.35; P less than .0001). Multivariable propensity-matched analysis showed a 6% absolute increase in retained gastric contents in the semaglutide group compared to controls (P less than .0001).

This increase appeared clinically relevant, as semaglutide use was associated with a higher rate of early procedure termination (OR, 3.09; P = 0.02) and recommendations for repeat endoscopies (OR, 3.61; P = 0.02), “indicating the degree of retained solid gastric contents was enough to limit the intended gastric mucosal examination,” the investigators wrote.

However, patients who underwent same-day colonoscopy, which included a 24-hour clear liquid fast leading up to the procedure, were less likely to have retained gastric contents (OR, 0.41; 95% CI, 0.23-0.73; P = 0.003), suggesting that extended fasting protocols may mitigate the risk of procedural complications.

“Patients with a history of gastroparesis are often advised to stop ingesting solid foods and maintain a clear liquid diet for a longer period than standard ASA guidance before anesthetized procedures,” Dr. Korlipara and colleagues wrote. “In our opinion, this recommendation should be considered in patients on long-term GLP-1RA therapy, in response to the findings reported in this study and others about the protective effects of a 24-hour liquid fast.”

Point-of-care gastric ultrasound may also be considered to evaluate patients at higher risk of retained stomach contents, they added, especially in patients with additional risk factors for delayed gastric emptying.

“Previously published data have linked prolonged gastric emptying delays in patients chronically using these medications,” they wrote. “Considering the effect on blood sugar and associated procedural risk, especially in patients taking this medication for diabetes management, more studies are warranted to determine the effect of medication on periprocedural complications and recommend repeat evaluation.”

After this study was released, new clinical guidance on the use of GLP-1RAs before surgery was co-published by AGA and four other societies. The guidance notes that, in most cases, patients can continue to take GLP-1RAs, but individual risk factors for complications should be assessed prior to surgery. The guidance cautions that patients at high risk for significant GI side effects should follow a liquid diet for 24 hours before a procedure and the anesthesia plan be adjusted accordingly. In rare cases, the procedure should be delayed.

Dr. Korlipara disclosed no conflicts of interest.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

An expert panel has published noninvasive test (NIT) cutoffs to identify patients with metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis who may benefit from resmetirom therapy.

This guidance document allows clinicians to use a variety of NITs to start and monitor resmetirom therapy, precluding the need for a biopsy, lead author Mazen Noureddin, MD, of Houston Research Institute, Houston Methodist Hospital in Texas, and colleagues reported.

Houston Methodist Hospital

“The recent conditional approval by the [Food and Drug Administration] of resmetirom ... presents a much-anticipated therapeutic option for patients with noncirrhotic advanced MASH,” the investigators wrote in Clinical Gastroenterology and Hepatology.

However, the approval also “presents important challenges,” they noted, “including how to noninvasively identify patients with fibrosis stages 2-3, and how to exclude patients with more advanced disease who should not be treated until further data emerge on the use of resmetirom in this population.”

To help identify which patients should get this new intervention, Noureddin and colleagues considered benchmarks from published literature, and conducted a post hoc analysis of phase 3 MASTERO-NASH trial data. Trial enrollment required at least three cardiometabolic risk factors and a vibration-controlled transient elastography (VCTE) prescreening within the past 3 months. The population included 888 patients with F2 or F3 disease.

Recommendations were split into three categories: treat with resmetirom, consider treating with resmetirom, and do not treat with resmetirom.

The recommendation to treat calls for a VCTE of 10-15 kPa, a magnetic resonance elastography (MRE) of 3.3-4.2 kPa, or an Enhanced Liver Fibrosis (ELF) score of 9.2-10.4, with the caveat that an ELF score below 9.8 requires a second NIT for confirmation. Alternatively, a positive composite score such as FibroScan–aspartate aminotransferase (FAST), MRI–AST (MAST), or MRE + Fibrosis-4 (MEFIB) may serve as grounds for treatment. For any of the previous, platelets must concurrently be at least 140 with no evidence of portal hypertension.

The recommendation to consider treatment depends upon a VCTE of 15.1-19.9 kPa, an MRE of 4.3-4.9 kPa, an ELF score of 10.5-11.3, or positive FAST, MAST, or MEFIB. Again, these require a concurrent platelet count of 140 and no portal hypertension.

Finally, patients should not be treated with resmetirom if they have a VCTE of 20 kPa or greater, an MRE of 5 kPa or greater, and an ELF score greater than 11.3.

Noureddin and colleagues also offered guidance on monitoring strategies, including follow-up at 3, 6, and 12 months.

At 3 months, the focus should be safety, including screening for drug-related liver injury and other adverse events that warrant cessation.

At 6 months, alanine aminotransferase (ALT) levels, VCTE, or MRI–proton density fat fraction (PDFF) tests can indicate early response, but treatment should generally continue regardless of results.

At 12 months, efficacy can be fully evaluated. ALT normalization, or improvement of more than 17 IU/L or more than 20%, along with a 30% or greater drop in VCTE, or at least 30% drop in liver fat on MRI-PDFF, serve as grounds for continuation.

Noureddin and colleagues noted that ALT improvement should be paired with corresponding improvements in imaging, such as a 30% reduction in MRI-PDFF. Even if ALT levels do not improve, a 30% or greater reduction in MRI-PDFF can still indicate a positive response; however, VCTE alone may not be sufficient to fully assess treatment response.

“Emerging data, particularly regarding the noninvasive assessment of treatment response, are likely to further modify patient selection, safety signals, and efficacy algorithms,” they concluded.This study was supported by the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, the John C. Martin Foundation, and the National Institute on Alcohol Abuse and Alcoholism. The investigators disclosed additional relationships with Novo Nordisk, Pfizer, Shire, and others.

Noninvasive surveillance with multitarget stool DNA testing or fecal immunochemical testing (FIT) could potentially match colonoscopy for reducing long-term colorectal cancer (CRC) incidence and mortality. It might also reduce colonoscopies by an estimated 15%-41%.

The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.

In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.

“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.

Netherlands Cancer Institute

Stanford University

Study Details

The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.

For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.

A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.

Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:

• 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
• 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR 
• 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold 

Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.

“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.

In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”

He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”

The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.

This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.

Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.

Ladabaum disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Noninvasive surveillance with multitarget stool DNA testing or fecal immunochemical testing (FIT) could potentially match colonoscopy for reducing long-term colorectal cancer (CRC) incidence and mortality. It might also reduce colonoscopies by an estimated 15%-41%.

The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.

In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.

“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.

Netherlands Cancer Institute

Stanford University

Study Details

The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.

For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.

A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.

Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:

• 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
• 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR 
• 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold 

Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.

“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.

In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”

He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”

The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.

This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.

Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.

Ladabaum disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Noninvasive surveillance with multitarget stool DNA testing or fecal immunochemical testing (FIT) could potentially match colonoscopy for reducing long-term colorectal cancer (CRC) incidence and mortality. It might also reduce colonoscopies by an estimated 15%-41%.

The greatest reduction would likely be achieved by annual FIT-based surveillance, especially with FIT FOB-Gold at a threshold of at least 32 µg/g feces, according to findings from the Dutch MOCCAS study published in Gastroenterology.

In this cross-sectional observational study, the multitarget DNA test outperformed FIT for detecting advanced precursor lesions, especially serrated polyps. According to long-term-impact mathematical modeling, however, DNA-based surveillance would be more costly than colonoscopy surveillance, whereas FIT would save costs.

“With the worldwide implementation of FIT-based screening programs, following a positive test, many more people enter surveillance programs after polypectomy. This results in an increased pressure on the colonoscopy capacity and healthcare budgets,” lead author Beatriz Carvalho, PhD, a molecular biologist in the Department of Pathology of the Netherlands Cancer Institute in Amsterdam, said in an interview.

Netherlands Cancer Institute

Stanford University

Study Details

The cross-sectional observational study included individuals aged 50-75 years who provided stool samples for the DNA test and two FITs. Test accuracy was calculated for all surveillance indications.

For the post-polypectomy indication only, which is the most common and associated with a relatively low CRC risk, the long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer model. Stool-based strategies were simulated to tune each test’s positivity threshold to obtain strategies that are at least as effective as colonoscopy surveillance.

A total of 3453 individuals had results for all stool tests and colonoscopy; among them, 2226 had previously undergone polypectomy, 1003 had a history of CRC, and 224 had a familial risk.

Areas under the receiver operating characteristic curve for advanced neoplasia were as follows:

• 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test
• 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR 
• 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold 

Stool-based surveillance was estimated to be at least as effective as colonoscopy surveillance and required 5.6 to 9.5 stool tests over a person’s lifetime. DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs.

“These findings provide a basis to embark on a prospective intervention study to assess the clinical utility of FIT as an alternative to colonoscopy surveillance in a post-polypectomy CRC surveillance population,” the authors wrote.

In the United States, Ladabaum said, it would likely be possible to find FIT-based strategies that closely approximate or match surveillance colonoscopy — “if we could deploy FIT with the required flexibility, for example, by adjusting the threshold and if the reference surveillance standard were somewhat relaxed compared with current guidelines.”

He worries, however, that if FIT for screening and FIT for surveillance were optimized at different hemoglobin detection thresholds, “there could be confusion and room for error in real-world clinical implementation.”

The authors called for research to increase understanding of the mechanisms underlying progression from adenomas to malignancy over time, which may yield better biomarkers to improve stool test accuracy.

This study was funded by the Alpe d’HuZes charity and the Dutch Cancer Society. Exact Sciences provided test equipment and performed multitarget stool DNA test analysis. Sentinel Diagnostics provided equipment and reagents.

Carvalho and Veerle M. H. Coupé, PhD, disclosed several patents pending and/or issued. Other coauthors disclosed multiple financial relationships with private companies, including Exact Sciences and Sentinel, for research support, travel, board membership, advisory or speaker fees, consulting, employment, stock ownership, or patents.

Ladabaum disclosed no competing interests relevant to his comments.

A version of this article appeared on Medscape.com.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is expected to bring a wave of added healthcare costs to Canada, with projections indicating an increase of almost C$2 billion (Canadian dollars) by 2050, according to a new study.

The expected surge reflects the growing prevalence of MASLD and its associated conditions, emphasizing the necessity for a comprehensive approach to address this escalating public health issue, reported lead author K. Ally Memedovich, BHSc, of the University of Calgary in Alberta, Canada, and colleagues.

K. Ally Memedovich

“The costs associated with the management of MASLD in Canada remain unknown but have been estimated as being very high,” the investigators wrote in Gastro Hep Advances. “Specifically, in one study from the United States, the healthcare costs and utilization of those with MASLD was nearly double that of patients without MASLD but with similar health status. This difference was largely due to increases in imaging, hospitalization, liver fibrosis assessment, laboratory tests, and outpatient visits.”

Although projections are available to estimate the future prevalence of MASLD in Canada, no models are available to predict the growing national economic burden, prompting the present study.

Memedovich and colleagues analyzed healthcare usage data from 6,358 patients diagnosed with MASLD disease in Calgary from 2018 to 2020. Using provincial administrative data, they calculated both liver-specific and total healthcare costs associated with different stages of liver fibrosis, ranging from F0/F1 (minimal fibrosis) to F4 (advanced fibrosis or cirrhosis).

The patients’ liver fibrosis stages were determined using liver stiffness measurements obtained through shear wave elastography. Average annual cost per patient was then calculated for each fibrosis stage by analyzing hospitalizations, ambulatory care, and physician claims data.

The annual average liver-specific cost per patient increased with severity of liver fibrosis; costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$7.02, C$35.30, C$60.46, and C$72.55, respectively. By 2050, liver-specific healthcare costs are projected to increase by C$51 million, reaching C$136 million Canada-wide.

Total healthcare costs were markedly higher; annual costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$397.90, C$781.53, C$2,881.84, and C$1,598.82, respectively. As a result, total healthcare costs are expected to rise by nearly C$2 billion, contributing to a Canadian healthcare burden of C$5.81 billion annually by 2050.

The study revealed that over 90% of the healthcare costs for MASLD patients were attributed not to liver disease itself but to the management of associated comorbidities such as diabetes, hypertension, mental illness, and obesity. For instance, diabetes was the most common reason for physician visits among MASLD patients, accounting for 65.2% of cases. One study limitation was exclusion of decompensated cirrhosis, liver cancer, or a liver transplant recipient because of low prevalence in this cohort, potentially contributing to low liver specific healthcare costs.

Memedovich and colleagues noted that chronic diseases account for approximately C$68 billion annually in direct healthcare costs in Canada, representing around 58% of total healthcare expenditures. Estimates suggest that 1% annual reduction in chronic disease prevalence could save C$107 billion over the course of 20 years.

“Therefore, an approach that focuses on preventing and managing chronic diseases overall is needed to reduce the burden of MASLD on the healthcare system,” they wrote. This study was funded by LiveRx via an Alberta Innovates grant. The investigators disclosed relationships with Gilead, Abbott, GSK, and others.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is expected to bring a wave of added healthcare costs to Canada, with projections indicating an increase of almost C$2 billion (Canadian dollars) by 2050, according to a new study.

The expected surge reflects the growing prevalence of MASLD and its associated conditions, emphasizing the necessity for a comprehensive approach to address this escalating public health issue, reported lead author K. Ally Memedovich, BHSc, of the University of Calgary in Alberta, Canada, and colleagues.

K. Ally Memedovich

“The costs associated with the management of MASLD in Canada remain unknown but have been estimated as being very high,” the investigators wrote in Gastro Hep Advances. “Specifically, in one study from the United States, the healthcare costs and utilization of those with MASLD was nearly double that of patients without MASLD but with similar health status. This difference was largely due to increases in imaging, hospitalization, liver fibrosis assessment, laboratory tests, and outpatient visits.”

Although projections are available to estimate the future prevalence of MASLD in Canada, no models are available to predict the growing national economic burden, prompting the present study.

Memedovich and colleagues analyzed healthcare usage data from 6,358 patients diagnosed with MASLD disease in Calgary from 2018 to 2020. Using provincial administrative data, they calculated both liver-specific and total healthcare costs associated with different stages of liver fibrosis, ranging from F0/F1 (minimal fibrosis) to F4 (advanced fibrosis or cirrhosis).

The patients’ liver fibrosis stages were determined using liver stiffness measurements obtained through shear wave elastography. Average annual cost per patient was then calculated for each fibrosis stage by analyzing hospitalizations, ambulatory care, and physician claims data.

The annual average liver-specific cost per patient increased with severity of liver fibrosis; costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$7.02, C$35.30, C$60.46, and C$72.55, respectively. By 2050, liver-specific healthcare costs are projected to increase by C$51 million, reaching C$136 million Canada-wide.

Total healthcare costs were markedly higher; annual costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$397.90, C$781.53, C$2,881.84, and C$1,598.82, respectively. As a result, total healthcare costs are expected to rise by nearly C$2 billion, contributing to a Canadian healthcare burden of C$5.81 billion annually by 2050.

The study revealed that over 90% of the healthcare costs for MASLD patients were attributed not to liver disease itself but to the management of associated comorbidities such as diabetes, hypertension, mental illness, and obesity. For instance, diabetes was the most common reason for physician visits among MASLD patients, accounting for 65.2% of cases. One study limitation was exclusion of decompensated cirrhosis, liver cancer, or a liver transplant recipient because of low prevalence in this cohort, potentially contributing to low liver specific healthcare costs.

Memedovich and colleagues noted that chronic diseases account for approximately C$68 billion annually in direct healthcare costs in Canada, representing around 58% of total healthcare expenditures. Estimates suggest that 1% annual reduction in chronic disease prevalence could save C$107 billion over the course of 20 years.

“Therefore, an approach that focuses on preventing and managing chronic diseases overall is needed to reduce the burden of MASLD on the healthcare system,” they wrote. This study was funded by LiveRx via an Alberta Innovates grant. The investigators disclosed relationships with Gilead, Abbott, GSK, and others.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is expected to bring a wave of added healthcare costs to Canada, with projections indicating an increase of almost C$2 billion (Canadian dollars) by 2050, according to a new study.

The expected surge reflects the growing prevalence of MASLD and its associated conditions, emphasizing the necessity for a comprehensive approach to address this escalating public health issue, reported lead author K. Ally Memedovich, BHSc, of the University of Calgary in Alberta, Canada, and colleagues.

K. Ally Memedovich

“The costs associated with the management of MASLD in Canada remain unknown but have been estimated as being very high,” the investigators wrote in Gastro Hep Advances. “Specifically, in one study from the United States, the healthcare costs and utilization of those with MASLD was nearly double that of patients without MASLD but with similar health status. This difference was largely due to increases in imaging, hospitalization, liver fibrosis assessment, laboratory tests, and outpatient visits.”

Although projections are available to estimate the future prevalence of MASLD in Canada, no models are available to predict the growing national economic burden, prompting the present study.

Memedovich and colleagues analyzed healthcare usage data from 6,358 patients diagnosed with MASLD disease in Calgary from 2018 to 2020. Using provincial administrative data, they calculated both liver-specific and total healthcare costs associated with different stages of liver fibrosis, ranging from F0/F1 (minimal fibrosis) to F4 (advanced fibrosis or cirrhosis).

The patients’ liver fibrosis stages were determined using liver stiffness measurements obtained through shear wave elastography. Average annual cost per patient was then calculated for each fibrosis stage by analyzing hospitalizations, ambulatory care, and physician claims data.

The annual average liver-specific cost per patient increased with severity of liver fibrosis; costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$7.02, C$35.30, C$60.46, and C$72.55, respectively. By 2050, liver-specific healthcare costs are projected to increase by C$51 million, reaching C$136 million Canada-wide.

Total healthcare costs were markedly higher; annual costs for patients with fibrosis stages F0/F1, F2, F3, and F4 were C$397.90, C$781.53, C$2,881.84, and C$1,598.82, respectively. As a result, total healthcare costs are expected to rise by nearly C$2 billion, contributing to a Canadian healthcare burden of C$5.81 billion annually by 2050.

The study revealed that over 90% of the healthcare costs for MASLD patients were attributed not to liver disease itself but to the management of associated comorbidities such as diabetes, hypertension, mental illness, and obesity. For instance, diabetes was the most common reason for physician visits among MASLD patients, accounting for 65.2% of cases. One study limitation was exclusion of decompensated cirrhosis, liver cancer, or a liver transplant recipient because of low prevalence in this cohort, potentially contributing to low liver specific healthcare costs.

Memedovich and colleagues noted that chronic diseases account for approximately C$68 billion annually in direct healthcare costs in Canada, representing around 58% of total healthcare expenditures. Estimates suggest that 1% annual reduction in chronic disease prevalence could save C$107 billion over the course of 20 years.

“Therefore, an approach that focuses on preventing and managing chronic diseases overall is needed to reduce the burden of MASLD on the healthcare system,” they wrote. This study was funded by LiveRx via an Alberta Innovates grant. The investigators disclosed relationships with Gilead, Abbott, GSK, and others.

More evidence suggests there is little risk in administering the live rotavirus vaccine to the babies of mothers on biologics during pregnancy for inflammatory bowel disease (IBD).

No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.

University of Calgary

The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.

“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.

“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.

They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.

Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.

“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.

“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.

The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.

Icahn School of Medicine at Mount Sinai

“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”

She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”

Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
 

The Study

The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.

For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.

The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.

As anticipated, infant immune function was normal regardless of circulating drug levels.

The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.

This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.

A version of this article first appeared on Medscape.com.

More evidence suggests there is little risk in administering the live rotavirus vaccine to the babies of mothers on biologics during pregnancy for inflammatory bowel disease (IBD).

No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.

University of Calgary

The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.

“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.

“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.

They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.

Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.

“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.

“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.

The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.

Icahn School of Medicine at Mount Sinai

“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”

She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”

Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
 

The Study

The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.

For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.

The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.

As anticipated, infant immune function was normal regardless of circulating drug levels.

The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.

This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.

A version of this article first appeared on Medscape.com.

More evidence suggests there is little risk in administering the live rotavirus vaccine to the babies of mothers on biologics during pregnancy for inflammatory bowel disease (IBD).

No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.

University of Calgary

The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.

“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.

“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.

They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.

Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.

“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.

“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.

The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.

Icahn School of Medicine at Mount Sinai

“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”

She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”

Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
 

The Study

The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.

For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.

The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.

As anticipated, infant immune function was normal regardless of circulating drug levels.

The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.

This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.

A version of this article first appeared on Medscape.com.

Potassium-competitive acid blocker vonoprazan is safe and effective for patients with heartburn from nonerosive reflux disease (NERD), according to investigators.

Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.

Yale School of Medicine

“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.

While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.

The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.

The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.

In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).

Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.

The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).

These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.

Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.

“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.

In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.

Potassium-competitive acid blocker vonoprazan is safe and effective for patients with heartburn from nonerosive reflux disease (NERD), according to investigators.

Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.

Yale School of Medicine

“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.

While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.

The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.

The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.

In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).

Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.

The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).

These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.

Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.

“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.

In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.

Potassium-competitive acid blocker vonoprazan is safe and effective for patients with heartburn from nonerosive reflux disease (NERD), according to investigators.

Benefits of vonoprazan were seen as soon as the first day of treatment and persisted through the 20-week extension period, lead author Loren Laine, MD, AGAF, of Yale School of Medicine, New Haven, Connecticut, and colleagues reported.

Yale School of Medicine

“A potential alternative to PPI therapy is a potassium-competitive acid blocker, a new class of antisecretory agents that provide more potent inhibition of gastric acid secretion than PPIs,” the investigators wrote in Clinical Gastroenterology and Hepatology.

While a small observational study found that 18 out of 26 patients (69%) with PPI-resistant NERD had improved symptoms with vonoprazan, subsequent randomized trials in Japan failed to meet their primary endpoints, Laine and colleagues noted. The present randomized trial was therefore conducted to determine how vonoprazan might help a US patient population.

The study involved 772 patients who reported heartburn at least 4 days per week during screening, but without erosive esophagitis on endoscopy. Participants were randomized into three groups: placebo, vonoprazan 10 mg, or vonoprazan 20 mg. These protocols were administered for 4 weeks, followed by a 20-week extension, in which placebo patients were rerandomized to receive one of the two vonoprazan dose levels.

The primary endpoint was the percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days) during the initial 4-week treatment period. The secondary endpoint, assessed during the same timeframe, was percentage of days without need for a rescue antacid.

In the 4-week placebo-controlled period, patients treated with vonoprazan 10 mg and 20 mg showed a significant improvement in heartburn-free days, compared with placebo. The percentage of 24-hour heartburn-free days was 27.7% in the placebo group vs 44.8% in the 10-mg vonoprazan group (least squares mean difference 17.1%; P < .0001) and 44.4% in the 20 mg vonoprazan group (least squares mean difference 16.7%; P < .0001).

Benefits of vonoprazan were seen as early as the first day of treatment, with 8.3% and 11.6% more patients in the 10-mg and 20-mg groups, respectively, experiencing a heartburn-free day, compared with placebo. By day 2, these differences increased to 18.1% and 23.2%, respectively.

The percentage of days without rescue antacid use was also significantly higher in both vonoprazan groups. Patients in the 10 mg and 20 mg groups had 63.3% and 61.2% of days without antacid use, respectively, compared with 47.6% in the placebo group (P < .0001 for both comparisons).

These benefits persisted throughout the 20-week extension period, with similar percentages of heartburn-free days across all groups. Mean percentages of 24-hour heartburn-free days ranged from 61% to 63% in the extension phase, while median percentages spanned 76%-79%.

Adverse events were infrequent and comparable across all groups. The most common adverse event was nausea, occurring slightly more frequently in the vonoprazan groups (2.3% in the 10-mg group and 3.1% in the 20-mg group) vs placebo (0.4%). Serious adverse events were rare and were deemed unrelated to treatment. No new safety signals were identified during the 20-week extension period. Increases in serum gastrin levels, a marker of acid suppression, returned to near baseline after discontinuation of vonoprazan.

“In conclusion, the potassium-competitive acid blocker vonoprazan was efficacious in reducing heartburn symptoms in patients with NERD, with the benefit appearing to begin as early as the first day of therapy,” Laine and colleagues wrote.

In July 2024, the Food and Drug Administration approved vonoprazan for treating heartburn in patients with nonerosive gastroesophageal reflux disease.This study was funded by Phathom Pharmaceuticals. The investigators disclosed additional relationships with Takeda, Medtronic, Carnot, and others.

Primary care screening for celiac disease (CD) in kids could improve health outcomes, and it appears cost effective over time, according to a Dutch analysis.

If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.

courtesy Leiden University

“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.

Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.

“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”

These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.

The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.

The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.

The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.

The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.

For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.

Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.

Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.

“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.

Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.

“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

Primary care screening for celiac disease (CD) in kids could improve health outcomes, and it appears cost effective over time, according to a Dutch analysis.

If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.

courtesy Leiden University

“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.

Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.

“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”

These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.

The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.

The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.

The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.

The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.

For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.

Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.

Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.

“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.

Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.

“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

Primary care screening for celiac disease (CD) in kids could improve health outcomes, and it appears cost effective over time, according to a Dutch analysis.

If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.

courtesy Leiden University

“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.

Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.

“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”

These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.

The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.

The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.

The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.

The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.

For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.

Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.

Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.

“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.

Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.

“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.

Compared with endoscopy, the Baveno VI criteria present a noninvasive and cost-effective method to detect high-risk varices in patients with Child-Pugh A cirrhosis, according to new research.

Although upper gastrointestinal endoscopy continues to be the gold standard for detecting varices, the Baveno VI criteria combine liver stiffness and platelet count values to rule out high-risk varices, which can save on endoscopy costs.

“The Baveno VI criteria can reduce the need for endoscopies in patients with cirrhosis, but it is important to ascertain if they are also cost-effective,” said senior author Emmanuel Tsochatzis, MD, professor of hepatology at the University College London Institute for Liver and Digestive Health and Royal Free Hospital in London.

Andrew McConnell/EASL

“Our findings confirm that the application of these criteria is highly cost-effective, and given the fact that they are also safe, should be considered for widespread implementation,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Baveno VI Criteria Analysis

On the basis of the Baveno VI Consensus, endoscopy screening can be avoided in patients with compensated advanced chronic liver disease and Child-Pugh A cirrhosis who have a platelet count > 150,000/mm³ and a liver stiffness measurement < 20 kPa. 

In addition, expanded Baveno VI criteria have suggested optimized cut-off values to avoid even more endoscopies — at a platelet value of > 110,000/mm³ and a liver stiffness < 25 kPa.

Previous research indicates that the expanded criteria could avoid double the number of endoscopies, the authors wrote, with a risk of missing high-risk varices in 1.6% of patients with the criteria and 0.6% of overall study participants. Both criteria have been validated in large groups of patients with compensated cirrhosis of different etiologies, but the cost-effectiveness hasn’t been analyzed.

Dr. Tsochatzis and colleagues created an analytical decision model to estimate the costs and benefits of using the Baveno VI criteria as compared with endoscopy as the standard of care among a hypothetical cohort of 1000 patients with Child-Pugh A cirrhosis. The research team looked at costs and clinical outcomes based on the United Kingdom National Health Service perspective at 1 year from diagnosis and then estimated the expected costs and outcomes at 5 years and 20 years, including factors such as liver disease progression and variceal bleeding.

As part of the model, the Baveno VI criteria were implemented at annual screenings with targeted endoscopy for patients who met the criteria, as compared with endoscopy as a biannual screening using esophagogastroduodenoscopy for everyone.

In general, the Baveno VI criteria were cost-effective compared with endoscopy in all analyses, including all time points, as well as deterministic and probabilistic sensitivity analyses. The cost of using the criteria was £67 per patient, as compared with £411 per patient for esophagogastroduodenoscopy.

For the 1000 patients, the criteria produced 0.16 additional quality-adjusted life years (QALYs) per patient at an incremental cost of £326, or about $443, over 5 years. This resulted in an incremental cost-effectiveness ratio (ICER) of £2081, or $2830, per additional QALY gained.

In addition, the incremental net monetary benefit of the Baveno VI criteria was £2808, or $3819, over 5 years per patient.

The results were also consistent and cost-effective in Canada and Spain using relevant cost inputs from those countries. In Canada, the ICER per QALY estimates were €3535, or $3712, over 5 years and €4610, or $4841, over 20 years. In Spain, the ICER per QALY estimates were €1966, or $2064, over 5 years and €2225, or $2336, over 20 years.
 

Baveno VI Considerations

Despite the small risk of false negatives, the Baveno VI criteria could avoid unnecessary endoscopies and provide significant cost savings, the study authors wrote.

“It should be mentioned, however, that sparing endoscopies could result in missing the incidental detection of esophageal and gastric cancers, particularly in patients with higher risk, such as those who misuse alcohol,” Dr. Tsochatzis said.

Future studies could investigate ways to broaden the applicability of the Baveno VI criteria to other patient subgroups, identify optimal cut-off points, and incorporate patients with systemic therapies.

“Baveno VI criteria can be safely used to avoid endoscopy in a substantial proportion of patients with compensated cirrhosis,” said Wayne Bai, MBChB, a gastroenterologist at Waikato Hospital and the University of Auckland in New Zealand.

Dr. Bai, who wasn’t involved with this study, has researched the Baveno VI criteria and participated in Baveno VII criteria meetings. In an analysis of more than two dozen studies, he and colleagues found that the Baveno VI criteria had a pooled 99% negative predictive value for ruling out high-risk varices and weren’t affected by the cause of cirrhosis. However, expanding the criteria had suboptimal performance in some cases.

Waikato Hospital

A version of this article first appeared on Medscape.com.

Compared with endoscopy, the Baveno VI criteria present a noninvasive and cost-effective method to detect high-risk varices in patients with Child-Pugh A cirrhosis, according to new research.

Although upper gastrointestinal endoscopy continues to be the gold standard for detecting varices, the Baveno VI criteria combine liver stiffness and platelet count values to rule out high-risk varices, which can save on endoscopy costs.

“The Baveno VI criteria can reduce the need for endoscopies in patients with cirrhosis, but it is important to ascertain if they are also cost-effective,” said senior author Emmanuel Tsochatzis, MD, professor of hepatology at the University College London Institute for Liver and Digestive Health and Royal Free Hospital in London.

Andrew McConnell/EASL

“Our findings confirm that the application of these criteria is highly cost-effective, and given the fact that they are also safe, should be considered for widespread implementation,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Baveno VI Criteria Analysis

On the basis of the Baveno VI Consensus, endoscopy screening can be avoided in patients with compensated advanced chronic liver disease and Child-Pugh A cirrhosis who have a platelet count > 150,000/mm³ and a liver stiffness measurement < 20 kPa. 

In addition, expanded Baveno VI criteria have suggested optimized cut-off values to avoid even more endoscopies — at a platelet value of > 110,000/mm³ and a liver stiffness < 25 kPa.

Previous research indicates that the expanded criteria could avoid double the number of endoscopies, the authors wrote, with a risk of missing high-risk varices in 1.6% of patients with the criteria and 0.6% of overall study participants. Both criteria have been validated in large groups of patients with compensated cirrhosis of different etiologies, but the cost-effectiveness hasn’t been analyzed.

Dr. Tsochatzis and colleagues created an analytical decision model to estimate the costs and benefits of using the Baveno VI criteria as compared with endoscopy as the standard of care among a hypothetical cohort of 1000 patients with Child-Pugh A cirrhosis. The research team looked at costs and clinical outcomes based on the United Kingdom National Health Service perspective at 1 year from diagnosis and then estimated the expected costs and outcomes at 5 years and 20 years, including factors such as liver disease progression and variceal bleeding.

As part of the model, the Baveno VI criteria were implemented at annual screenings with targeted endoscopy for patients who met the criteria, as compared with endoscopy as a biannual screening using esophagogastroduodenoscopy for everyone.

In general, the Baveno VI criteria were cost-effective compared with endoscopy in all analyses, including all time points, as well as deterministic and probabilistic sensitivity analyses. The cost of using the criteria was £67 per patient, as compared with £411 per patient for esophagogastroduodenoscopy.

For the 1000 patients, the criteria produced 0.16 additional quality-adjusted life years (QALYs) per patient at an incremental cost of £326, or about $443, over 5 years. This resulted in an incremental cost-effectiveness ratio (ICER) of £2081, or $2830, per additional QALY gained.

In addition, the incremental net monetary benefit of the Baveno VI criteria was £2808, or $3819, over 5 years per patient.

The results were also consistent and cost-effective in Canada and Spain using relevant cost inputs from those countries. In Canada, the ICER per QALY estimates were €3535, or $3712, over 5 years and €4610, or $4841, over 20 years. In Spain, the ICER per QALY estimates were €1966, or $2064, over 5 years and €2225, or $2336, over 20 years.
 

Baveno VI Considerations

Despite the small risk of false negatives, the Baveno VI criteria could avoid unnecessary endoscopies and provide significant cost savings, the study authors wrote.

“It should be mentioned, however, that sparing endoscopies could result in missing the incidental detection of esophageal and gastric cancers, particularly in patients with higher risk, such as those who misuse alcohol,” Dr. Tsochatzis said.

Future studies could investigate ways to broaden the applicability of the Baveno VI criteria to other patient subgroups, identify optimal cut-off points, and incorporate patients with systemic therapies.

“Baveno VI criteria can be safely used to avoid endoscopy in a substantial proportion of patients with compensated cirrhosis,” said Wayne Bai, MBChB, a gastroenterologist at Waikato Hospital and the University of Auckland in New Zealand.

Dr. Bai, who wasn’t involved with this study, has researched the Baveno VI criteria and participated in Baveno VII criteria meetings. In an analysis of more than two dozen studies, he and colleagues found that the Baveno VI criteria had a pooled 99% negative predictive value for ruling out high-risk varices and weren’t affected by the cause of cirrhosis. However, expanding the criteria had suboptimal performance in some cases.

Waikato Hospital

A version of this article first appeared on Medscape.com.

Compared with endoscopy, the Baveno VI criteria present a noninvasive and cost-effective method to detect high-risk varices in patients with Child-Pugh A cirrhosis, according to new research.

Although upper gastrointestinal endoscopy continues to be the gold standard for detecting varices, the Baveno VI criteria combine liver stiffness and platelet count values to rule out high-risk varices, which can save on endoscopy costs.

“The Baveno VI criteria can reduce the need for endoscopies in patients with cirrhosis, but it is important to ascertain if they are also cost-effective,” said senior author Emmanuel Tsochatzis, MD, professor of hepatology at the University College London Institute for Liver and Digestive Health and Royal Free Hospital in London.

Andrew McConnell/EASL

“Our findings confirm that the application of these criteria is highly cost-effective, and given the fact that they are also safe, should be considered for widespread implementation,” he said.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Baveno VI Criteria Analysis

On the basis of the Baveno VI Consensus, endoscopy screening can be avoided in patients with compensated advanced chronic liver disease and Child-Pugh A cirrhosis who have a platelet count > 150,000/mm³ and a liver stiffness measurement < 20 kPa. 

In addition, expanded Baveno VI criteria have suggested optimized cut-off values to avoid even more endoscopies — at a platelet value of > 110,000/mm³ and a liver stiffness < 25 kPa.

Previous research indicates that the expanded criteria could avoid double the number of endoscopies, the authors wrote, with a risk of missing high-risk varices in 1.6% of patients with the criteria and 0.6% of overall study participants. Both criteria have been validated in large groups of patients with compensated cirrhosis of different etiologies, but the cost-effectiveness hasn’t been analyzed.

Dr. Tsochatzis and colleagues created an analytical decision model to estimate the costs and benefits of using the Baveno VI criteria as compared with endoscopy as the standard of care among a hypothetical cohort of 1000 patients with Child-Pugh A cirrhosis. The research team looked at costs and clinical outcomes based on the United Kingdom National Health Service perspective at 1 year from diagnosis and then estimated the expected costs and outcomes at 5 years and 20 years, including factors such as liver disease progression and variceal bleeding.

As part of the model, the Baveno VI criteria were implemented at annual screenings with targeted endoscopy for patients who met the criteria, as compared with endoscopy as a biannual screening using esophagogastroduodenoscopy for everyone.

In general, the Baveno VI criteria were cost-effective compared with endoscopy in all analyses, including all time points, as well as deterministic and probabilistic sensitivity analyses. The cost of using the criteria was £67 per patient, as compared with £411 per patient for esophagogastroduodenoscopy.

For the 1000 patients, the criteria produced 0.16 additional quality-adjusted life years (QALYs) per patient at an incremental cost of £326, or about $443, over 5 years. This resulted in an incremental cost-effectiveness ratio (ICER) of £2081, or $2830, per additional QALY gained.

In addition, the incremental net monetary benefit of the Baveno VI criteria was £2808, or $3819, over 5 years per patient.

The results were also consistent and cost-effective in Canada and Spain using relevant cost inputs from those countries. In Canada, the ICER per QALY estimates were €3535, or $3712, over 5 years and €4610, or $4841, over 20 years. In Spain, the ICER per QALY estimates were €1966, or $2064, over 5 years and €2225, or $2336, over 20 years.
 

Baveno VI Considerations

Despite the small risk of false negatives, the Baveno VI criteria could avoid unnecessary endoscopies and provide significant cost savings, the study authors wrote.

“It should be mentioned, however, that sparing endoscopies could result in missing the incidental detection of esophageal and gastric cancers, particularly in patients with higher risk, such as those who misuse alcohol,” Dr. Tsochatzis said.

Future studies could investigate ways to broaden the applicability of the Baveno VI criteria to other patient subgroups, identify optimal cut-off points, and incorporate patients with systemic therapies.

“Baveno VI criteria can be safely used to avoid endoscopy in a substantial proportion of patients with compensated cirrhosis,” said Wayne Bai, MBChB, a gastroenterologist at Waikato Hospital and the University of Auckland in New Zealand.

Dr. Bai, who wasn’t involved with this study, has researched the Baveno VI criteria and participated in Baveno VII criteria meetings. In an analysis of more than two dozen studies, he and colleagues found that the Baveno VI criteria had a pooled 99% negative predictive value for ruling out high-risk varices and weren’t affected by the cause of cirrhosis. However, expanding the criteria had suboptimal performance in some cases.

Waikato Hospital

A version of this article first appeared on Medscape.com.