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MASH Driving Global Epidemic of Primary Liver Cancer
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Reviewing this study for GI & Hepatology News, but not involved in it, Scott L. Friedman, MD, AGAF, chief emeritus of the Division of Liver Diseases at Mount Sinai Health System in New York City and director of the newly established multidisciplinary Mount Sinai Institute for Liver Research, said the increase in primary liver cancer burden revealed by the research has been recognized for several years, especially among liver specialists, and is worsening, particularly in America.
“This is most evident in the changing composition of liver transplant waiting lists, which include a diminishing number of patients with chronic viral hepatitis, and a growing fraction of patients with steatotic liver disease, either from MASH alone or with concurrent alcohol-associated liver disease,” Friedman said. He noted that apart from the brain, the liver is the body’s least understood organ.
Friedman said that an urgent need exists for increased awareness of and screening for steatotic liver disease in primary care and general medicine practices – especially in patients with type 2 diabetes, about 70% of whom typically have steatosis – as well as those with features of the metabolic syndrome, with obesity, type 2 diabetes, lipid abnormalities and hypertension. “Awareness of metabolic-associated liver disease and MASH among patients and providers is still inadequate,” he said. “However, now that there’s a newly approved drug, Rezdiffra [resmetirom] – and more likely in the coming years – early detection and treatment of MASH will become essential to prevent its progression to cirrhosis and PLC through specific medications.”
Once patients with MASH have more advanced fibrosis, Friedman noted, regular screening for PLC is essential to detect early cancers that are still curable either by liver resection, liver transplant, or direct ablation of small tumors. “Unfortunately, it is not unusual for patients to present with an incurable PLC without realizing they had any underlying liver disease, since MASH is not associated with specific liver symptoms.”
Friedman disclosed no competing interests relevant to his comments.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
Although the incidence of PLC from most etiologies is declining, MASH and alcohol-related liver disease (ALD) are exceptions.
A recent analysis in Clinical Gastroenterology and Hepatology found a near doubling of cases in from 2000 to 2021 in data from the 2024 Global Burden of Disease study.
The analysis assessed age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.
The burden of MASH-associated primary liver cancer (PLC) is rising rapidly while, thanks to effective suppressive treatments, the incidence of PLC from viral hepatitis is declining.
“Given the shifting epidemiology and limited global data, this analysis was timely to provide updated, comprehensive estimates using the GBD 2021 database,” lead authors Ju Dong Yang, MD, MS, and Karn Wijarnpreecha, MD, MPH, told GI & Hepatology News in a joint email. Yang is an associate professor and medical director of the Liver Cancer Program at Cedars-Sinai Medical Center in Los Angeles, and Wijarnpreecha is a transplant hepatologist in the of Division of Gastroenterology at University of Arizona College of Medicine in Phoenix. “Our study helps identify regions, populations, and sex-specific trends that are most affected and informs global policy response.”
Interestingly,the United States ranks among the top three countries worldwide in terms of MASH-associated PLC burden, with nearly 3,400 newly diagnosed cases reported in 2021 alone. The Americas in general experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%, 95% CI, 2.02–2.16), age-standardized death rate (APC, 1.96%; 95% CI, 1.69–2.23), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63–2.30) from MASH-associated PLC.
Globally, there were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period.
Among different etiologies, the global study found that only MASH-associated PLC had increased mortality rates, for an annual percent change of +0.46 (95% confidence interval [CI], .33%–.59%). Africa and low-sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC.
MASH promotes PLC through chronic liver inflammation, oxidative stress, lipotoxicity, and fibrosis, which together create a procarcinogenic environment even in the absence of cirrhosis. “This distinct pathway makes MASH-associated PLC harder to detect early, especially when cirrhosis is not yet evident,” Yang and Wijarnpreecha said.
By gender, DALYs increased in females (APC, .24%, 95% CI, .06–.42) but remained stable in males. “Males have higher absolute rates of MASH-associated PLC in terms of incidence and DALYs. However, our study found that the rate of increase in MASH-associated PLC-related disability is steeper in females. This suggests a growing burden among women, possibly related to aging, hormonal changes, and cumulative metabolic risk,” the authors said. In terms of age, “while our study did not assess age at onset, separate analyses have shown that both MASH-associated and alcohol-associated liver cancer are rising among younger individuals.”
Yang and Wijarnpreecha emphasized the need for a multi-pronged remedial strategy, including broad public health policies targeting obesity and metabolic syndrome and better risk stratification tools such as no-invasive biomarkers and genetic profiling. They called for investment in liver cancer surveillance, especially in populations at risk, and special attention to sex disparities and health equity across regions.
“We’re entering a new era of liver cancer epidemiology, where MASLD is taking center stage. Clinicians must recognize that MASH can progress to liver cancer even without cirrhosis,” they said. “Early diagnosis and metabolic intervention may be the best tools to curb this trend, and sex-based approaches to risk stratification and treatment may be essential moving forward.”
Yang’s research is supported by the National Institutes of Health. He consults for AstraZeneca, Eisai, Exact Sciences, and FujiFilm Medical Sciences.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Colonoscopy Screening Effective in 45- to 49-Year-Olds
Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.
The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.
The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma.
About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.
There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.
Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.
The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.
Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.
The Kaiser research is “really powerful information,” she said.
“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.
The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.
Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.
But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.
Patel said that estimate is “spot on” in terms of other estimates.
“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.
Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.
Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.
Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.
Calderwood and Patel reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.
The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.
The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma.
About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.
There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.
Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.
The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.
Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.
The Kaiser research is “really powerful information,” she said.
“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.
The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.
Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.
But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.
Patel said that estimate is “spot on” in terms of other estimates.
“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.
Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.
Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.
Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.
Calderwood and Patel reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Researchers at Kaiser Permanente Northern California sought to compare yields between the two age groups to assess how a change in guidance in 2021 urging screening in the younger cohort was borne out in a real-world setting.
The researchers published their findings in JAMA, concluding that the results supported screening colonoscopy in 45- to 49-year-olds.
The study compared 4380 individuals aged 45-49 years, with 7651 who were aged 50-54. All of them underwent their first colonoscopy during 2021 to 2024. Thirty-five percent of the younger group and 40% of the older group had any adenoma.
About 4% of each group had an advanced adenoma, 10% had any sessile serrated lesion, a little under 2% had an advanced serrated lesion, and 0.1% in each group had colorectal cancer.
There were no significant differences in neoplasia prevalence between the groups by sex. The authors did note that the study group included more Asian individuals (30%) than in the general population.
Swati G. Patel, MD, MS, director of the Gastrointestinal Hereditary Cancer Program at the University of Colorado Anschutz Medical Center, Denver, said the Kaiser study is important because its data was aggregated after the US Preventive Services Task Force lowered the screening age in 2021.
The Kaiser research “validates the initial studies” done to support that recommendation and the 2022 consensus statement by the US Multi-Society Task Force on Colorectal Cancer, which also advocated screening in 45- to 49-year-olds.
Even though the new JAMA study found a similar rate of cancers and precursor lesions as in previous trials, it provides “reinforcement of the rationale for decreasing the screening age,” Patel, the lead author on the consensus statement, told GI & Hepatology News.
The Kaiser research is “really powerful information,” she said.
“It certainly validates our current guidance to start screening for colorectal cancer at age 45,” said Audrey Calderwood, MD, director of the GI Cancer Risk and Prevention Clinic at the Geisel School of Medicine, Dartmouth, New Hampshire.
The Kaiser data provides granular information to share with younger patients who might think that they don’t need screening because they are healthy and don’t have symptoms, said Calderwood, also director of the Comprehensive Gastroenterology Center at Dartmouth Hitchcock Medical Center.
Colon cancer rates for Americans under age 50 have been steadily rising for the past decade, hitting about 10 cases per 100,000 in 2022, according to the National Cancer Institute (NCI). In 2023, about 73% of eligible 50- to 75-year-olds received colorectal cancer screening based on the most recent guidelines, according to the NCI.
But screening rates in the under-50 age group are much lower. Researchers estimated in a study that only about 34.5% of those aged 45-49 received colorectal cancer screening, which included colonoscopy, stool-based tests, and CT colonography.
Patel said that estimate is “spot on” in terms of other estimates.
“I think there’s a perception that it’s a cancer of older adults and that young healthy people don’t need to worry about it,” she said, adding that getting the word out to younger Americans is a “PR challenge,” in part because of squeamishness about discussing anything to do with stool and changes in how they access information.
Calderwood agreed. Younger people “aren’t chatting to their friends about” colon cancer screening the way they might about mammography, said Calderwood.
Both she and Patel noted that educating the public was an ongoing project, but that a physician’s recommendation was key.
Patel said she hoped that data provided in the Kaiser study might help “dismantle the systemic skepticism around decreasing the age recommendation” for screening.
Calderwood and Patel reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
Less Invasive Screening May Identify Barrett’s Esophagus Earlier
, a small comparative study in US veterans found.
BE is up to three times more prevalent in veterans than in the general population.
This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.
Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.
Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.
“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”
The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.
Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.
Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.
Study Details
The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.
Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.
“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”
All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.
“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.
Procedural Anxiety
Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.
Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”
Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”
The Bottom Line
“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.
This study was funded by a Department of Defense award.
Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.
A version of this article appeared on Medscape.com.
, a small comparative study in US veterans found.
BE is up to three times more prevalent in veterans than in the general population.
This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.
Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.
Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.
“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”
The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.
Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.
Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.
Study Details
The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.
Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.
“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”
All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.
“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.
Procedural Anxiety
Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.
Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”
Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”
The Bottom Line
“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.
This study was funded by a Department of Defense award.
Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.
A version of this article appeared on Medscape.com.
, a small comparative study in US veterans found.
BE is up to three times more prevalent in veterans than in the general population.
This and other minimally invasive approaches may reduce patient anxiety and increase screening rates, according to investigators led by Katarina B. Greer, MD, MS, of the VA Northeast Ohio Healthcare System and Case Western University in Cleveland. Such screening platforms are expected to open a window on improved prognosis for EAC by offering well-tolerated, office-based testing, the authors wrote in The American Journal of Gastroenterology.
Greer and colleagues compared standard upper endoscopy with EsoCheck (EC), a nonendoscopic esophageal balloon cell-sampling device coupled with EsoGuard (EG), a DNA-based precancer screening assay, with standard upper endoscopy, an FDA-approved minimally invasive alternative.
Sensitivity and specificity of combined EC/EG for esophagogastroduodenoscopy (EGD)-detected BE/EAC were 92.9% (95% CI, 66.1-99.8) and 72.2% (95% CI, 62.1-80.8), respectively. Positive and negative predictive values were 32.5% (95% CI, 18.6-49.1) and 98.6% (95% CI, 92.4-100), respectively.
“With its strong negative predictive power, this screening modality could be a first-line tool available to a greater number of patients,” Greer and associates wrote. “Data from this test support the notion that EC could be performed as a triaging test to increase the yield of diagnostic upper endoscopy 2.5-fold.”
The US rates of EAC have increased more than six-fold in the past four decades and continue to rise. In 2023, 21,560 cases of EAC were diagnosed here. The prognosis for EAC is still poor, with fewer than 22% of patients surviving beyond 5 years.
Current guidelines recommend sedated EGD for patients with chronic gastroesophageal reflux disease (GERD) and additional BE risk factors such as smoking, obesity, and family history. This strategy, however, often fails to detect BE when symptoms are well controlled with over-the-counter or physician-prescribed therapies, Greer and colleagues noted. It also fails to detect BE in individuals without GERD, who comprise 40% of those who develop EAC.
Fewer than 5% of EACs are diagnosed as early-stage lesions caught by surveillance of patients with previously detected BE.
Study Details
The researchers recruited veterans meeting American College of Gastroenterology criteria for endoscopic BE and EAC screening at the Louis Stokes Cleveland Veterans Affairs Medical Center.
Of 782 eligible veterans, 130 (16.6%) entered the study and 124 completed screening. Common reasons for nonparticipation included completion of upper endoscopy outside of the VA healthcare system, lack of interest in joining a research study, and no recommendation for screening from referring gastroenterology or primary care providers. Eligible candidates had gastroesophageal reflux disorder plus three additional risk factors, such as smoking, higher BMI, male sex, age 50 years or older, and family history. The mean number of risk factors was 4.1.
“Available data suggest that family history is the strongest predictor of BE diagnosis, as prevalence of BE among those with family history was 23%,” Greer’s group wrote. “This points to high priority of pursuing screening in patients with family history of the condition, followed by patients who share multiple risk factors.”
All participants completed unsedated EC-guided distal esophageal sampling followed by a sedated EGD on the same day. The prevalence of BE/EAC was 12.9% (n = 14/2), based on standard EGD.
“The study was not powered to prospectively determine EC diagnostic accuracy for subgroups of nondysplastic and dysplastic BE and EAC. These data are reported for this device in development studies but not available for our study population,” the authors wrote. In comparison, they noted, the Cytosponge-TFF3, another nonendoscopic screening device for EAC and BE, exhibited lower sensitivity of 79.5%-87.2%, depending on lesion length, but higher specificity of 92.4%.
Procedural Anxiety
Baseline scores on the short-form six-item Spielberger State-Trait Anxiety Inventory-6 (STAI-6) revealed notable levels of periprocedural anxiety. STAI-6 scores range from 20 to 80, with higher scores indicating more severe anxiety. In the VA study, scores ranged from 20 to 60, and most domains constituting the scores were the same before and after the procedure. Participants did, however, report a statistically significant decrease in sense of worry after EC and reported good tolerability for both EC and EG.
Offering an outsider’s perspective on the study, Joshua Sloan, DO, an esophageal gastroenterologist at University of Minnesota Medical Center in Minneapolis, said that with the acceleration of US rates of EAC, developing a nonendoscopic screening tool to improve identification of Barrett’s and perhaps early EAC is important. “The study by Greer et al helps support the use of nonendoscopic screening with EsoCheck and EsoGuard to identify these conditions,” he told GI & Hepatology News. “It will be interesting to see similar studies in the non-VA population as well. As the study notes, veterans are an enriched population with a higher prevalence of Barrett’s esophagus.”
Ultimately, Sloan added, “the hope is to increase our ability to identify and manage BE before it becomes EAC. Nonendoscopic screening tools have the potential to increase diagnosis and funnel the appropriate patients for endoscopic surveillance.”
The Bottom Line
“Calculations regarding effectiveness of the two-step screening strategy afforded by EC indicate that the burden of screening would be reduced by at least half (53%),” the authors wrote. Since the estimated size of the US screen-eligible population ranges from 19.7 million to 120.1 million, noninvasive tools could significantly decrease EGD procedures. A formal cost effectiveness analysis is being conducted and will be published separately.
This study was funded by a Department of Defense award.
Co-Author Chak reported device patents assigned to Case Western Reserve University and licensed to Lucid Diagnostics. The other authors had no competing interests to declare. Sloan disclosed speaking and/or advisory work for Sanofi-Regeneron, Phathom Pharmaceuticals, and Takeda Pharmaceuticals unrelated to his comments.
A version of this article appeared on Medscape.com.
Intestinal Ultrasound Shows Promise in Prognosis of Early Crohn’s Disease
, a prospective, population-based cohort of newly diagnosed patients in Denmark reported.
Adding to the growing body of evidence on the utility of this noninvasive imaging tool in monitoring disease activity in the newly diagnosed, the multicenter study published in Clinical Gastroenterology and Hepatology characterized ultrasonographic features at diagnosis and evaluated IUS’s prognostic value. Existing literature has focused on patients with long-standing disease.
Investigators led by first author Gorm R. Madsen, MD, PhD, of the Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults at Copenhagen University Hospital, observed continued improvement in most IUS parameters throughout the first year. “Our findings thereby emphasize the role of IUS in improving patient management, and its use in patient risk stratification already at diagnosis,” the investigators wrote.
Some 38% of patients reached ultrasonic transmural remission within 3 months of diagnosis, an achievement associated with higher rates of sustained steroid-free clinical remission and reduced need for treatment escalation.
“Ultrasonic transmural remission is achievable early in Crohn’s disease and is associated with favorable outcomes, underscoring the value of intestinal ultrasound in early disease management,” the researchers wrote.
Study Details
While IUS is increasingly recognized for monitoring CD, little was known about its prognostic value early in the disease course. “We aimed to determine whether sonographic inflammation at diagnosis — and particularly the achievement pftransmural remission after 3 months — could predict future outcomes,” Madsen told GI & Hepatology News. “This is important, as early identification of patients at risk of surgery or treatment escalation may help guide therapy decisions more effectively.”
From May 2021 to April 2023, 201 patients (mean age, 35 years; 54.2% men) with new adult-onset CD were followed by IUS and monitored with symptomatic, biochemical, and endoscopic evaluations.
After 3 months, transmural remission was achieved more often by patients with colonic disease, and no associations were found between sonographic inflammation at diagnosis and diagnostic delay.
“We were positively surprised. Nearly 40% of newly diagnosed Crohn’s patients achieved transmural remission within 3 months — a higher proportion than seen in earlier studies, which mostly focused on long-standing or trial-selected populations,” Madsen said. “It was also striking how strongly early IUS findings predicted the need for surgery, outperforming endoscopy and biomarkers.”
In other findings, transmural remission at 3 months was significantly associated with steroid-free clinical remission at both 3 months and all subsequent follow-ups within the first year. It was also linked to a lower risk for treatment escalation during the follow-up through to 12 months: 26% vs 53% (P =.003). At 12 months, 41% had achieved transmural remission.
Higher baseline body mass index significantly reduced the likelihood of 12-month transmural remission. For overweight, the odds ratio (OR) was 0.34 (95% CI, 0.12-0.94), while for obesity, the OR was 0.16 (95% CI, 0.04-0.73).
The International Bowel Ultrasound Segmental Activity Score in the terminal ileum at diagnosis emerged as the best predictor of ileocecal resection during the first year, with an optimal threshold of 63 (area under the curve, 0.92; sensitivity, 100%; specificity, 73%).
The use of IUS has expanded considerably in the past 3 years, and in 2024, the American Gastroenterological Association updated its clinical practice guidance on the role of this modality in inflammatory bowel disease.
IUS is noninvasive, radiation-free, inexpensive, and doable at the bedside with immediate results, Madsen said. “For patients, this means less anxiety and discomfort. For healthcare systems, it enables faster clinical decisions, reduced need for endoscopy or MRI, and closer disease monitoring, particularly valuable in treat-to-target strategies.”
In terms of limitations, however, IUS is operator-dependent and consistent training is crucial, he added. “Certain anatomical regions, particularly the proximal small bowel, can be more challenging to evaluate. Additionally, while IUS is highly effective for assessing inflammatory activity, it becomes more difficult to accurately assess disease involvement when inflammation extends beyond approximately 20 cm of the small bowel.”
Key Insights
Commenting on the Danish study from a US perspective, Anna L. Silverman, MD, a gastroenterology fellow at Icahn School of Medicine at Mount Sinai in New York City, agreed the findings in adult patients with newly diagnosed, rather than long-standing, CD contribute to the growing body of evidence supporting IUS’s applicability for both treatment monitoring and prognosis.
“By focusing on early-stage CD, the study provides clearer insights into initial disease activity and response to therapy, reinforcing the value of this noninvasive, point-of-care modality,” she told GI & Hepatology News. “These findings enhance our understanding of IUS as a tool to help guide early management decisions in CD.”
Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital and an associate professor at Harvard Medical School, both in Boston, concurred that this is an important study. “It includes newly diagnosed patients — so a very ‘clean’ cohort in terms of not being influenced by confounders,” he told GI & Hepatology News.
“We don’t fully know yet the best treatment target in CD, and this study highlights the importance of early transmural healing in determining outcomes at 1 year,” he noted. In addition, the study highlighted a convenient tool that can increasingly be applied at point of care in the United States. “Colonoscopy at 3 months is not practical and has low patient acceptability, so using IUS in this circumstance would have value and impact.”
Ananthakrishnan pointed to several unanswered questions, however. “Are there patients who may not have healing early but may take some extra time to achieve transmural remission, and if so, what are their outcomes? What is the best timepoint for transmural healing assessment? What is the incremental value of measuring it at 3 vs 6 months?”
In addition, he wondered, how much is the added value of IUS over clinical symptoms and/or markers such as calprotectin and C-reactive protein? “In the subset of patients with clinical and transmural remission, there was no difference in endoscopic outcomes at 1 year, so this is an unanswered question,” Ananthakrishnan said.
This study was funded by an unrestricted grant from the Novo Nordisk Foundation.
Madsen reported receiving a speaker’s fee from Tillotts. Multiple coauthors disclosed having various financial relationships with numerous private-sector companies, including Novo Nordisk. Silverman and Ananthakrishnan reported having no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
, a prospective, population-based cohort of newly diagnosed patients in Denmark reported.
Adding to the growing body of evidence on the utility of this noninvasive imaging tool in monitoring disease activity in the newly diagnosed, the multicenter study published in Clinical Gastroenterology and Hepatology characterized ultrasonographic features at diagnosis and evaluated IUS’s prognostic value. Existing literature has focused on patients with long-standing disease.
Investigators led by first author Gorm R. Madsen, MD, PhD, of the Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults at Copenhagen University Hospital, observed continued improvement in most IUS parameters throughout the first year. “Our findings thereby emphasize the role of IUS in improving patient management, and its use in patient risk stratification already at diagnosis,” the investigators wrote.
Some 38% of patients reached ultrasonic transmural remission within 3 months of diagnosis, an achievement associated with higher rates of sustained steroid-free clinical remission and reduced need for treatment escalation.
“Ultrasonic transmural remission is achievable early in Crohn’s disease and is associated with favorable outcomes, underscoring the value of intestinal ultrasound in early disease management,” the researchers wrote.
Study Details
While IUS is increasingly recognized for monitoring CD, little was known about its prognostic value early in the disease course. “We aimed to determine whether sonographic inflammation at diagnosis — and particularly the achievement pftransmural remission after 3 months — could predict future outcomes,” Madsen told GI & Hepatology News. “This is important, as early identification of patients at risk of surgery or treatment escalation may help guide therapy decisions more effectively.”
From May 2021 to April 2023, 201 patients (mean age, 35 years; 54.2% men) with new adult-onset CD were followed by IUS and monitored with symptomatic, biochemical, and endoscopic evaluations.
After 3 months, transmural remission was achieved more often by patients with colonic disease, and no associations were found between sonographic inflammation at diagnosis and diagnostic delay.
“We were positively surprised. Nearly 40% of newly diagnosed Crohn’s patients achieved transmural remission within 3 months — a higher proportion than seen in earlier studies, which mostly focused on long-standing or trial-selected populations,” Madsen said. “It was also striking how strongly early IUS findings predicted the need for surgery, outperforming endoscopy and biomarkers.”
In other findings, transmural remission at 3 months was significantly associated with steroid-free clinical remission at both 3 months and all subsequent follow-ups within the first year. It was also linked to a lower risk for treatment escalation during the follow-up through to 12 months: 26% vs 53% (P =.003). At 12 months, 41% had achieved transmural remission.
Higher baseline body mass index significantly reduced the likelihood of 12-month transmural remission. For overweight, the odds ratio (OR) was 0.34 (95% CI, 0.12-0.94), while for obesity, the OR was 0.16 (95% CI, 0.04-0.73).
The International Bowel Ultrasound Segmental Activity Score in the terminal ileum at diagnosis emerged as the best predictor of ileocecal resection during the first year, with an optimal threshold of 63 (area under the curve, 0.92; sensitivity, 100%; specificity, 73%).
The use of IUS has expanded considerably in the past 3 years, and in 2024, the American Gastroenterological Association updated its clinical practice guidance on the role of this modality in inflammatory bowel disease.
IUS is noninvasive, radiation-free, inexpensive, and doable at the bedside with immediate results, Madsen said. “For patients, this means less anxiety and discomfort. For healthcare systems, it enables faster clinical decisions, reduced need for endoscopy or MRI, and closer disease monitoring, particularly valuable in treat-to-target strategies.”
In terms of limitations, however, IUS is operator-dependent and consistent training is crucial, he added. “Certain anatomical regions, particularly the proximal small bowel, can be more challenging to evaluate. Additionally, while IUS is highly effective for assessing inflammatory activity, it becomes more difficult to accurately assess disease involvement when inflammation extends beyond approximately 20 cm of the small bowel.”
Key Insights
Commenting on the Danish study from a US perspective, Anna L. Silverman, MD, a gastroenterology fellow at Icahn School of Medicine at Mount Sinai in New York City, agreed the findings in adult patients with newly diagnosed, rather than long-standing, CD contribute to the growing body of evidence supporting IUS’s applicability for both treatment monitoring and prognosis.
“By focusing on early-stage CD, the study provides clearer insights into initial disease activity and response to therapy, reinforcing the value of this noninvasive, point-of-care modality,” she told GI & Hepatology News. “These findings enhance our understanding of IUS as a tool to help guide early management decisions in CD.”
Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital and an associate professor at Harvard Medical School, both in Boston, concurred that this is an important study. “It includes newly diagnosed patients — so a very ‘clean’ cohort in terms of not being influenced by confounders,” he told GI & Hepatology News.
“We don’t fully know yet the best treatment target in CD, and this study highlights the importance of early transmural healing in determining outcomes at 1 year,” he noted. In addition, the study highlighted a convenient tool that can increasingly be applied at point of care in the United States. “Colonoscopy at 3 months is not practical and has low patient acceptability, so using IUS in this circumstance would have value and impact.”
Ananthakrishnan pointed to several unanswered questions, however. “Are there patients who may not have healing early but may take some extra time to achieve transmural remission, and if so, what are their outcomes? What is the best timepoint for transmural healing assessment? What is the incremental value of measuring it at 3 vs 6 months?”
In addition, he wondered, how much is the added value of IUS over clinical symptoms and/or markers such as calprotectin and C-reactive protein? “In the subset of patients with clinical and transmural remission, there was no difference in endoscopic outcomes at 1 year, so this is an unanswered question,” Ananthakrishnan said.
This study was funded by an unrestricted grant from the Novo Nordisk Foundation.
Madsen reported receiving a speaker’s fee from Tillotts. Multiple coauthors disclosed having various financial relationships with numerous private-sector companies, including Novo Nordisk. Silverman and Ananthakrishnan reported having no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
, a prospective, population-based cohort of newly diagnosed patients in Denmark reported.
Adding to the growing body of evidence on the utility of this noninvasive imaging tool in monitoring disease activity in the newly diagnosed, the multicenter study published in Clinical Gastroenterology and Hepatology characterized ultrasonographic features at diagnosis and evaluated IUS’s prognostic value. Existing literature has focused on patients with long-standing disease.
Investigators led by first author Gorm R. Madsen, MD, PhD, of the Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults at Copenhagen University Hospital, observed continued improvement in most IUS parameters throughout the first year. “Our findings thereby emphasize the role of IUS in improving patient management, and its use in patient risk stratification already at diagnosis,” the investigators wrote.
Some 38% of patients reached ultrasonic transmural remission within 3 months of diagnosis, an achievement associated with higher rates of sustained steroid-free clinical remission and reduced need for treatment escalation.
“Ultrasonic transmural remission is achievable early in Crohn’s disease and is associated with favorable outcomes, underscoring the value of intestinal ultrasound in early disease management,” the researchers wrote.
Study Details
While IUS is increasingly recognized for monitoring CD, little was known about its prognostic value early in the disease course. “We aimed to determine whether sonographic inflammation at diagnosis — and particularly the achievement pftransmural remission after 3 months — could predict future outcomes,” Madsen told GI & Hepatology News. “This is important, as early identification of patients at risk of surgery or treatment escalation may help guide therapy decisions more effectively.”
From May 2021 to April 2023, 201 patients (mean age, 35 years; 54.2% men) with new adult-onset CD were followed by IUS and monitored with symptomatic, biochemical, and endoscopic evaluations.
After 3 months, transmural remission was achieved more often by patients with colonic disease, and no associations were found between sonographic inflammation at diagnosis and diagnostic delay.
“We were positively surprised. Nearly 40% of newly diagnosed Crohn’s patients achieved transmural remission within 3 months — a higher proportion than seen in earlier studies, which mostly focused on long-standing or trial-selected populations,” Madsen said. “It was also striking how strongly early IUS findings predicted the need for surgery, outperforming endoscopy and biomarkers.”
In other findings, transmural remission at 3 months was significantly associated with steroid-free clinical remission at both 3 months and all subsequent follow-ups within the first year. It was also linked to a lower risk for treatment escalation during the follow-up through to 12 months: 26% vs 53% (P =.003). At 12 months, 41% had achieved transmural remission.
Higher baseline body mass index significantly reduced the likelihood of 12-month transmural remission. For overweight, the odds ratio (OR) was 0.34 (95% CI, 0.12-0.94), while for obesity, the OR was 0.16 (95% CI, 0.04-0.73).
The International Bowel Ultrasound Segmental Activity Score in the terminal ileum at diagnosis emerged as the best predictor of ileocecal resection during the first year, with an optimal threshold of 63 (area under the curve, 0.92; sensitivity, 100%; specificity, 73%).
The use of IUS has expanded considerably in the past 3 years, and in 2024, the American Gastroenterological Association updated its clinical practice guidance on the role of this modality in inflammatory bowel disease.
IUS is noninvasive, radiation-free, inexpensive, and doable at the bedside with immediate results, Madsen said. “For patients, this means less anxiety and discomfort. For healthcare systems, it enables faster clinical decisions, reduced need for endoscopy or MRI, and closer disease monitoring, particularly valuable in treat-to-target strategies.”
In terms of limitations, however, IUS is operator-dependent and consistent training is crucial, he added. “Certain anatomical regions, particularly the proximal small bowel, can be more challenging to evaluate. Additionally, while IUS is highly effective for assessing inflammatory activity, it becomes more difficult to accurately assess disease involvement when inflammation extends beyond approximately 20 cm of the small bowel.”
Key Insights
Commenting on the Danish study from a US perspective, Anna L. Silverman, MD, a gastroenterology fellow at Icahn School of Medicine at Mount Sinai in New York City, agreed the findings in adult patients with newly diagnosed, rather than long-standing, CD contribute to the growing body of evidence supporting IUS’s applicability for both treatment monitoring and prognosis.
“By focusing on early-stage CD, the study provides clearer insights into initial disease activity and response to therapy, reinforcing the value of this noninvasive, point-of-care modality,” she told GI & Hepatology News. “These findings enhance our understanding of IUS as a tool to help guide early management decisions in CD.”
Ashwin Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital and an associate professor at Harvard Medical School, both in Boston, concurred that this is an important study. “It includes newly diagnosed patients — so a very ‘clean’ cohort in terms of not being influenced by confounders,” he told GI & Hepatology News.
“We don’t fully know yet the best treatment target in CD, and this study highlights the importance of early transmural healing in determining outcomes at 1 year,” he noted. In addition, the study highlighted a convenient tool that can increasingly be applied at point of care in the United States. “Colonoscopy at 3 months is not practical and has low patient acceptability, so using IUS in this circumstance would have value and impact.”
Ananthakrishnan pointed to several unanswered questions, however. “Are there patients who may not have healing early but may take some extra time to achieve transmural remission, and if so, what are their outcomes? What is the best timepoint for transmural healing assessment? What is the incremental value of measuring it at 3 vs 6 months?”
In addition, he wondered, how much is the added value of IUS over clinical symptoms and/or markers such as calprotectin and C-reactive protein? “In the subset of patients with clinical and transmural remission, there was no difference in endoscopic outcomes at 1 year, so this is an unanswered question,” Ananthakrishnan said.
This study was funded by an unrestricted grant from the Novo Nordisk Foundation.
Madsen reported receiving a speaker’s fee from Tillotts. Multiple coauthors disclosed having various financial relationships with numerous private-sector companies, including Novo Nordisk. Silverman and Ananthakrishnan reported having no competing interests relevant to their comments.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
EoE Prevalence in US Reaches 1 in 700, Costs $1B Annually
, according to recent research.
Although EoE has been considered a rare disease, the chronic condition is becoming more common, and healthcare providers should expect to encounter EoE in clinical settings, the study authors wrote.
“Our last assessment of the prevalence and burden of EoE was more than 10 years ago, and we had a strong suspicion we would continue to see increased numbers of patients with EoE and an increasing cost burden related to the condition in the United States,” said senior author Evan S. Dellon, MD, MPH, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill, North Carolina.
“EoE is becoming more common,” Dellon said. “Healthcare providers should expect to see EoE in their practices, including in the primary care setting, emergency departments, allergy practices, GI [gastrointestinal] practices, ENT clinics, and endoscopy suites.”
The study was published in Clinical Gastroenterology and Hepatology.
Estimating EoE Prevalence
Dellon and colleagues analyzed the Merative MarketScan Commercial Claims and Encounters and Medicare Fee-for-Service databases to calculate the annual prevalence of EoE, as well as age- and sex-stratified estimates standardized to the US population. They also calculated healthcare utilization, including medications and endoscopic procedures, to estimate annual EoE-associated costs. Since the EoE billing code was introduced in 2008, the analysis included 2009-2022 MarketScan and 2009-2017 Medicare data.
In the MarketScan database, the research team identified 20,435 EoE cases in 2022, with a mean age of 38 years, 16% younger than 18 years, 62% men, and 41% with a comorbid allergic disease code. The most common symptoms and diagnoses were dysphagia (39%), abdominal pain or dyspepsia (24%), and esophageal stricture (19%). Over time, patients also had previous codes for comorbid allergic diseases (64%), dysphagia (62%), or esophageal stricture (32%).
In the Medicare database, the research team identified 1913 EoE cases in 2017, with a mean age of 73 years, 47% men, 90% non-Hispanic White, and 36% with a comorbid allergic disease. The most common symptoms and diagnoses were dysphagia (49%), abdominal pain or dyspepsia (35%), and esophageal stricture (30%). Over time, patients also had codes for comorbid allergic diseases (64%), dysphagia (65%), or esophageal stricture (42%).
The database numbers translated to EoE prevalences of about 163 cases per 100,000 people in MarketScan in 2022 and 64 cases per 100,000 people in Medicare in 2017. Since 2009, there has been a fivefold increase in prevalence in both databases.
In MarketScan, the prevalence was higher among men than among women, at 204 vs 122 cases per 100,000 people. For both sexes, peak prevalence occurred between ages 40 and 44.
In Medicare, prevalence was also higher among men than among women, at 79 vs 55 cases per 100,000 people. Peak prevalence occurred between ages 65 and 69.
Standardized to the US population, EoE prevalence was 142.5 cases per 100,000 people, extrapolating to 472,380 cases. The overall prevalence was approximately 1 in 700, with rates of 1 in 617 for those younger than 65 years and 1 in 1562 for those aged ≥ 65 years.
“The rapidly increasing prevalence year over year for the entire timeframe of the study was surprising, as were our estimates of the total number of EoE patients in the US, which suggests that EoE is no longer a rare disease and is now seen in about 1 in 700 people,” Dellon said. “This almost triples our prior estimates of 1 in 2000 from 10 years ago, with all trends suggesting that the prevalence will continue to increase.”
Calculating EoE Costs
In terms of procedures, endoscopy with dilation or biopsy was used in about 60%-70% of patients with EoE in both MarketScan and Medicare during the years analyzed. In addition, upper endoscopy with biopsy was coded in 80%-90% of patients, guidewire-based dilation in 11%-17% of patients, and balloon-based dilation in 13%-20% of patients.
In terms of prescription medications, proton pump inhibitors (41%) and topical steroids (26%) were the most common in MarketScan in 2022, as well as in Medicare in 2017, at 32% and 9%, respectively.
When looking at costs by age and sex, the male cohort with the highest costs was aged 10-14 years, estimated at $106.7 million. Among the female cohort, the highest costs were associated with ages 15-19, estimated at $46.5 million.
Overall, total EoE-associated healthcare costs were estimated to be $1.04 billion in 2017, and when adjusted for inflation, the costs were estimated at $1.32 billion in 2024. This is likely an underestimate, the authors wrote, given that EoE prevalence has likely increased for ages 65 or older since 2017 and for all ages since 2022.
“Researching the prevalence and costs is essential to improving patient care by highlighting the growing burden of this recently recognized and growing chronic disease, guiding policy and insurer decisions, and advocating for better access to effective treatments and support for patients,” said Joy Chang, MD, assistant professor of medicine in the Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.Chang, who wasn’t involved with this study, specializes in eosinophilic GI diseases and researches patient-physician preferences and decision-making in EoE care.
“Clinicians should remain vigilant for symptoms, utilize guideline-based diagnostic approaches, and consider both medical and dietary treatment strategies to optimize patient outcomes and reduce long-term costs,” she said. “Increased awareness and timely intervention can help mitigate the growing impact of this chronic condition.”
The study was supported by a National Institutes of Health grant and used resources from the University of North Carolina Center for Gastrointestinal Biology and Disease. Dellon reported receiving research funding from and having consultant roles with numerous pharmaceutical companies and organizations. Chang reported having no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to recent research.
Although EoE has been considered a rare disease, the chronic condition is becoming more common, and healthcare providers should expect to encounter EoE in clinical settings, the study authors wrote.
“Our last assessment of the prevalence and burden of EoE was more than 10 years ago, and we had a strong suspicion we would continue to see increased numbers of patients with EoE and an increasing cost burden related to the condition in the United States,” said senior author Evan S. Dellon, MD, MPH, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill, North Carolina.
“EoE is becoming more common,” Dellon said. “Healthcare providers should expect to see EoE in their practices, including in the primary care setting, emergency departments, allergy practices, GI [gastrointestinal] practices, ENT clinics, and endoscopy suites.”
The study was published in Clinical Gastroenterology and Hepatology.
Estimating EoE Prevalence
Dellon and colleagues analyzed the Merative MarketScan Commercial Claims and Encounters and Medicare Fee-for-Service databases to calculate the annual prevalence of EoE, as well as age- and sex-stratified estimates standardized to the US population. They also calculated healthcare utilization, including medications and endoscopic procedures, to estimate annual EoE-associated costs. Since the EoE billing code was introduced in 2008, the analysis included 2009-2022 MarketScan and 2009-2017 Medicare data.
In the MarketScan database, the research team identified 20,435 EoE cases in 2022, with a mean age of 38 years, 16% younger than 18 years, 62% men, and 41% with a comorbid allergic disease code. The most common symptoms and diagnoses were dysphagia (39%), abdominal pain or dyspepsia (24%), and esophageal stricture (19%). Over time, patients also had previous codes for comorbid allergic diseases (64%), dysphagia (62%), or esophageal stricture (32%).
In the Medicare database, the research team identified 1913 EoE cases in 2017, with a mean age of 73 years, 47% men, 90% non-Hispanic White, and 36% with a comorbid allergic disease. The most common symptoms and diagnoses were dysphagia (49%), abdominal pain or dyspepsia (35%), and esophageal stricture (30%). Over time, patients also had codes for comorbid allergic diseases (64%), dysphagia (65%), or esophageal stricture (42%).
The database numbers translated to EoE prevalences of about 163 cases per 100,000 people in MarketScan in 2022 and 64 cases per 100,000 people in Medicare in 2017. Since 2009, there has been a fivefold increase in prevalence in both databases.
In MarketScan, the prevalence was higher among men than among women, at 204 vs 122 cases per 100,000 people. For both sexes, peak prevalence occurred between ages 40 and 44.
In Medicare, prevalence was also higher among men than among women, at 79 vs 55 cases per 100,000 people. Peak prevalence occurred between ages 65 and 69.
Standardized to the US population, EoE prevalence was 142.5 cases per 100,000 people, extrapolating to 472,380 cases. The overall prevalence was approximately 1 in 700, with rates of 1 in 617 for those younger than 65 years and 1 in 1562 for those aged ≥ 65 years.
“The rapidly increasing prevalence year over year for the entire timeframe of the study was surprising, as were our estimates of the total number of EoE patients in the US, which suggests that EoE is no longer a rare disease and is now seen in about 1 in 700 people,” Dellon said. “This almost triples our prior estimates of 1 in 2000 from 10 years ago, with all trends suggesting that the prevalence will continue to increase.”
Calculating EoE Costs
In terms of procedures, endoscopy with dilation or biopsy was used in about 60%-70% of patients with EoE in both MarketScan and Medicare during the years analyzed. In addition, upper endoscopy with biopsy was coded in 80%-90% of patients, guidewire-based dilation in 11%-17% of patients, and balloon-based dilation in 13%-20% of patients.
In terms of prescription medications, proton pump inhibitors (41%) and topical steroids (26%) were the most common in MarketScan in 2022, as well as in Medicare in 2017, at 32% and 9%, respectively.
When looking at costs by age and sex, the male cohort with the highest costs was aged 10-14 years, estimated at $106.7 million. Among the female cohort, the highest costs were associated with ages 15-19, estimated at $46.5 million.
Overall, total EoE-associated healthcare costs were estimated to be $1.04 billion in 2017, and when adjusted for inflation, the costs were estimated at $1.32 billion in 2024. This is likely an underestimate, the authors wrote, given that EoE prevalence has likely increased for ages 65 or older since 2017 and for all ages since 2022.
“Researching the prevalence and costs is essential to improving patient care by highlighting the growing burden of this recently recognized and growing chronic disease, guiding policy and insurer decisions, and advocating for better access to effective treatments and support for patients,” said Joy Chang, MD, assistant professor of medicine in the Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.Chang, who wasn’t involved with this study, specializes in eosinophilic GI diseases and researches patient-physician preferences and decision-making in EoE care.
“Clinicians should remain vigilant for symptoms, utilize guideline-based diagnostic approaches, and consider both medical and dietary treatment strategies to optimize patient outcomes and reduce long-term costs,” she said. “Increased awareness and timely intervention can help mitigate the growing impact of this chronic condition.”
The study was supported by a National Institutes of Health grant and used resources from the University of North Carolina Center for Gastrointestinal Biology and Disease. Dellon reported receiving research funding from and having consultant roles with numerous pharmaceutical companies and organizations. Chang reported having no relevant disclosures.
A version of this article appeared on Medscape.com.
, according to recent research.
Although EoE has been considered a rare disease, the chronic condition is becoming more common, and healthcare providers should expect to encounter EoE in clinical settings, the study authors wrote.
“Our last assessment of the prevalence and burden of EoE was more than 10 years ago, and we had a strong suspicion we would continue to see increased numbers of patients with EoE and an increasing cost burden related to the condition in the United States,” said senior author Evan S. Dellon, MD, MPH, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill, North Carolina.
“EoE is becoming more common,” Dellon said. “Healthcare providers should expect to see EoE in their practices, including in the primary care setting, emergency departments, allergy practices, GI [gastrointestinal] practices, ENT clinics, and endoscopy suites.”
The study was published in Clinical Gastroenterology and Hepatology.
Estimating EoE Prevalence
Dellon and colleagues analyzed the Merative MarketScan Commercial Claims and Encounters and Medicare Fee-for-Service databases to calculate the annual prevalence of EoE, as well as age- and sex-stratified estimates standardized to the US population. They also calculated healthcare utilization, including medications and endoscopic procedures, to estimate annual EoE-associated costs. Since the EoE billing code was introduced in 2008, the analysis included 2009-2022 MarketScan and 2009-2017 Medicare data.
In the MarketScan database, the research team identified 20,435 EoE cases in 2022, with a mean age of 38 years, 16% younger than 18 years, 62% men, and 41% with a comorbid allergic disease code. The most common symptoms and diagnoses were dysphagia (39%), abdominal pain or dyspepsia (24%), and esophageal stricture (19%). Over time, patients also had previous codes for comorbid allergic diseases (64%), dysphagia (62%), or esophageal stricture (32%).
In the Medicare database, the research team identified 1913 EoE cases in 2017, with a mean age of 73 years, 47% men, 90% non-Hispanic White, and 36% with a comorbid allergic disease. The most common symptoms and diagnoses were dysphagia (49%), abdominal pain or dyspepsia (35%), and esophageal stricture (30%). Over time, patients also had codes for comorbid allergic diseases (64%), dysphagia (65%), or esophageal stricture (42%).
The database numbers translated to EoE prevalences of about 163 cases per 100,000 people in MarketScan in 2022 and 64 cases per 100,000 people in Medicare in 2017. Since 2009, there has been a fivefold increase in prevalence in both databases.
In MarketScan, the prevalence was higher among men than among women, at 204 vs 122 cases per 100,000 people. For both sexes, peak prevalence occurred between ages 40 and 44.
In Medicare, prevalence was also higher among men than among women, at 79 vs 55 cases per 100,000 people. Peak prevalence occurred between ages 65 and 69.
Standardized to the US population, EoE prevalence was 142.5 cases per 100,000 people, extrapolating to 472,380 cases. The overall prevalence was approximately 1 in 700, with rates of 1 in 617 for those younger than 65 years and 1 in 1562 for those aged ≥ 65 years.
“The rapidly increasing prevalence year over year for the entire timeframe of the study was surprising, as were our estimates of the total number of EoE patients in the US, which suggests that EoE is no longer a rare disease and is now seen in about 1 in 700 people,” Dellon said. “This almost triples our prior estimates of 1 in 2000 from 10 years ago, with all trends suggesting that the prevalence will continue to increase.”
Calculating EoE Costs
In terms of procedures, endoscopy with dilation or biopsy was used in about 60%-70% of patients with EoE in both MarketScan and Medicare during the years analyzed. In addition, upper endoscopy with biopsy was coded in 80%-90% of patients, guidewire-based dilation in 11%-17% of patients, and balloon-based dilation in 13%-20% of patients.
In terms of prescription medications, proton pump inhibitors (41%) and topical steroids (26%) were the most common in MarketScan in 2022, as well as in Medicare in 2017, at 32% and 9%, respectively.
When looking at costs by age and sex, the male cohort with the highest costs was aged 10-14 years, estimated at $106.7 million. Among the female cohort, the highest costs were associated with ages 15-19, estimated at $46.5 million.
Overall, total EoE-associated healthcare costs were estimated to be $1.04 billion in 2017, and when adjusted for inflation, the costs were estimated at $1.32 billion in 2024. This is likely an underestimate, the authors wrote, given that EoE prevalence has likely increased for ages 65 or older since 2017 and for all ages since 2022.
“Researching the prevalence and costs is essential to improving patient care by highlighting the growing burden of this recently recognized and growing chronic disease, guiding policy and insurer decisions, and advocating for better access to effective treatments and support for patients,” said Joy Chang, MD, assistant professor of medicine in the Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.Chang, who wasn’t involved with this study, specializes in eosinophilic GI diseases and researches patient-physician preferences and decision-making in EoE care.
“Clinicians should remain vigilant for symptoms, utilize guideline-based diagnostic approaches, and consider both medical and dietary treatment strategies to optimize patient outcomes and reduce long-term costs,” she said. “Increased awareness and timely intervention can help mitigate the growing impact of this chronic condition.”
The study was supported by a National Institutes of Health grant and used resources from the University of North Carolina Center for Gastrointestinal Biology and Disease. Dellon reported receiving research funding from and having consultant roles with numerous pharmaceutical companies and organizations. Chang reported having no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
GLP-1s Treat and Even Reverse Some Forms of Liver Disease
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
Clinicians Can Prescribe the Cure for Hepatitis C: Most Kids Never Get It
HCV cases in children are rising, yet access to treatment is limited, especially for Black children, according to a new retrospective cohort analysis published in Pediatrics. Treatment entails direct-acting antiviral agents, for which 95% of patients have no detectable trace of the virus 12 weeks after treatment.
“HCV is a silent killer,” said Megan Rose Curtis, MD, MS, the lead author of the study. “It can be asymptomatic for many years until the third decade of life if a child is infected perinatally” and does not receive treatment.
The prevalence of HCV in pregnant people jumped 16-fold between 1998 and 2018 to 5.3 cases per every 1000 pregnancies, and these patients can transmit the disease perinatally. Many people are unaware they are infected.
Curtis, based at Washington University in St. Louis School of Medicine, St. Louis, Missouri, and her team analyzed electronic medical records of children diagnosed with HCV born over an 18-year period starting in 2000 using the TriNetX Research Network. They also included data on prescriptions for direct-acting antivirals, appointments with healthcare providers, and race and ethnicity.
The sample included 928 children with HCV (52.3% women; 55.9% White) and excluded children whose HCV had spontaneously cleared.
A little over one third (32%) of children had seen a clinician for HCV care, which was defined as having in their record an antiviral prescription, a fibrosis stage, an order for an HCV genotype test, or a diagnosis of the disease.
Even fewer children (12%) were prescribed an antiviral.
Children with certain characteristics were more likely to receive care, the researchers found. For instance, children born between 2014 and 2018 (P = .008) and those diagnosed at age 0-3 years (P = .03) were most likely to see a clinician and receive treatment.
The current recommended treatment regimen for pediatric HCV — glecaprevir/pibrentasvir (Mavyret) or sofosbuvir/velpatasvir (Epclusa) — became available in 2017.
Hispanic/Latinx and White children were 120% and 240% more likely than Black children, respectively, to have received care (odds ratio [OR], 2.20; 95% CI, 1.05-4.59 and OR, 3.44; 95% CI, 1.89-6.28). Children living in southern states were less likely to have seen a doctor for HCV treatment.
Curtis said children might not receive treatment because their caregivers do not bring them to follow-up appointments, possibly because they struggle with stable housing or transportation. Insurance companies also sometimes will not pay for the treatment.
“If you have a golden opportunity to see someone in your office, it might be the only chance someone offers them HCV treatment. It can have a huge and transformative impact on someone’s life,” she said.
Jenelle Ferry, MD, a neonatologist at Pediatrix Medical Group in Tampa, Florida, said clinicians should routinely screen children and refer caregivers to a pediatric hepatologist for further management.
Pediatricians who suspect HCV in their patients should order a test for viral nucleic acid or viral load or request a polymerase chain reaction test.
Curtis noted that more than half of children clear the infection on their own by age 3, the age at which treatment can also begin. Treatment may also not be the right option for those who cannot swallow the medicine, which is available in oral pellets for children.
Greg Marchand, MD, an OB/GYN at the Marchand Institute for Minimally Invasive Surgery in Mesa, Arizona, said the research illuminates a “huge missed opportunity” to help children.
“If left untreated, these children risk serious liver complications like cirrhosis, liver cancer, high medical costs, and even death,” he said.
Marchand said clinicians must be aware of the guidelines for testing people who are pregnant and infants. In 2020, the US Centers for Disease Control and Prevention recommended universal HCV antibody screening during every pregnancy.
“There’s still hope that treatment rates will improve as both doctors and families become more familiar with” the newer drugs, he said.
No financial disclosures were reported.
The authors of this study were supported by various grants and awards, including from the National Institutes of Health, the James and Audrey Foster MGH Research Scholar Award, the Charles A. King Trust Postdoctoral Research Fellowship, and the Boston University Clinical and Translational Science Institute.
A version of this article appeared on Medscape.com.
HCV cases in children are rising, yet access to treatment is limited, especially for Black children, according to a new retrospective cohort analysis published in Pediatrics. Treatment entails direct-acting antiviral agents, for which 95% of patients have no detectable trace of the virus 12 weeks after treatment.
“HCV is a silent killer,” said Megan Rose Curtis, MD, MS, the lead author of the study. “It can be asymptomatic for many years until the third decade of life if a child is infected perinatally” and does not receive treatment.
The prevalence of HCV in pregnant people jumped 16-fold between 1998 and 2018 to 5.3 cases per every 1000 pregnancies, and these patients can transmit the disease perinatally. Many people are unaware they are infected.
Curtis, based at Washington University in St. Louis School of Medicine, St. Louis, Missouri, and her team analyzed electronic medical records of children diagnosed with HCV born over an 18-year period starting in 2000 using the TriNetX Research Network. They also included data on prescriptions for direct-acting antivirals, appointments with healthcare providers, and race and ethnicity.
The sample included 928 children with HCV (52.3% women; 55.9% White) and excluded children whose HCV had spontaneously cleared.
A little over one third (32%) of children had seen a clinician for HCV care, which was defined as having in their record an antiviral prescription, a fibrosis stage, an order for an HCV genotype test, or a diagnosis of the disease.
Even fewer children (12%) were prescribed an antiviral.
Children with certain characteristics were more likely to receive care, the researchers found. For instance, children born between 2014 and 2018 (P = .008) and those diagnosed at age 0-3 years (P = .03) were most likely to see a clinician and receive treatment.
The current recommended treatment regimen for pediatric HCV — glecaprevir/pibrentasvir (Mavyret) or sofosbuvir/velpatasvir (Epclusa) — became available in 2017.
Hispanic/Latinx and White children were 120% and 240% more likely than Black children, respectively, to have received care (odds ratio [OR], 2.20; 95% CI, 1.05-4.59 and OR, 3.44; 95% CI, 1.89-6.28). Children living in southern states were less likely to have seen a doctor for HCV treatment.
Curtis said children might not receive treatment because their caregivers do not bring them to follow-up appointments, possibly because they struggle with stable housing or transportation. Insurance companies also sometimes will not pay for the treatment.
“If you have a golden opportunity to see someone in your office, it might be the only chance someone offers them HCV treatment. It can have a huge and transformative impact on someone’s life,” she said.
Jenelle Ferry, MD, a neonatologist at Pediatrix Medical Group in Tampa, Florida, said clinicians should routinely screen children and refer caregivers to a pediatric hepatologist for further management.
Pediatricians who suspect HCV in their patients should order a test for viral nucleic acid or viral load or request a polymerase chain reaction test.
Curtis noted that more than half of children clear the infection on their own by age 3, the age at which treatment can also begin. Treatment may also not be the right option for those who cannot swallow the medicine, which is available in oral pellets for children.
Greg Marchand, MD, an OB/GYN at the Marchand Institute for Minimally Invasive Surgery in Mesa, Arizona, said the research illuminates a “huge missed opportunity” to help children.
“If left untreated, these children risk serious liver complications like cirrhosis, liver cancer, high medical costs, and even death,” he said.
Marchand said clinicians must be aware of the guidelines for testing people who are pregnant and infants. In 2020, the US Centers for Disease Control and Prevention recommended universal HCV antibody screening during every pregnancy.
“There’s still hope that treatment rates will improve as both doctors and families become more familiar with” the newer drugs, he said.
No financial disclosures were reported.
The authors of this study were supported by various grants and awards, including from the National Institutes of Health, the James and Audrey Foster MGH Research Scholar Award, the Charles A. King Trust Postdoctoral Research Fellowship, and the Boston University Clinical and Translational Science Institute.
A version of this article appeared on Medscape.com.
HCV cases in children are rising, yet access to treatment is limited, especially for Black children, according to a new retrospective cohort analysis published in Pediatrics. Treatment entails direct-acting antiviral agents, for which 95% of patients have no detectable trace of the virus 12 weeks after treatment.
“HCV is a silent killer,” said Megan Rose Curtis, MD, MS, the lead author of the study. “It can be asymptomatic for many years until the third decade of life if a child is infected perinatally” and does not receive treatment.
The prevalence of HCV in pregnant people jumped 16-fold between 1998 and 2018 to 5.3 cases per every 1000 pregnancies, and these patients can transmit the disease perinatally. Many people are unaware they are infected.
Curtis, based at Washington University in St. Louis School of Medicine, St. Louis, Missouri, and her team analyzed electronic medical records of children diagnosed with HCV born over an 18-year period starting in 2000 using the TriNetX Research Network. They also included data on prescriptions for direct-acting antivirals, appointments with healthcare providers, and race and ethnicity.
The sample included 928 children with HCV (52.3% women; 55.9% White) and excluded children whose HCV had spontaneously cleared.
A little over one third (32%) of children had seen a clinician for HCV care, which was defined as having in their record an antiviral prescription, a fibrosis stage, an order for an HCV genotype test, or a diagnosis of the disease.
Even fewer children (12%) were prescribed an antiviral.
Children with certain characteristics were more likely to receive care, the researchers found. For instance, children born between 2014 and 2018 (P = .008) and those diagnosed at age 0-3 years (P = .03) were most likely to see a clinician and receive treatment.
The current recommended treatment regimen for pediatric HCV — glecaprevir/pibrentasvir (Mavyret) or sofosbuvir/velpatasvir (Epclusa) — became available in 2017.
Hispanic/Latinx and White children were 120% and 240% more likely than Black children, respectively, to have received care (odds ratio [OR], 2.20; 95% CI, 1.05-4.59 and OR, 3.44; 95% CI, 1.89-6.28). Children living in southern states were less likely to have seen a doctor for HCV treatment.
Curtis said children might not receive treatment because their caregivers do not bring them to follow-up appointments, possibly because they struggle with stable housing or transportation. Insurance companies also sometimes will not pay for the treatment.
“If you have a golden opportunity to see someone in your office, it might be the only chance someone offers them HCV treatment. It can have a huge and transformative impact on someone’s life,” she said.
Jenelle Ferry, MD, a neonatologist at Pediatrix Medical Group in Tampa, Florida, said clinicians should routinely screen children and refer caregivers to a pediatric hepatologist for further management.
Pediatricians who suspect HCV in their patients should order a test for viral nucleic acid or viral load or request a polymerase chain reaction test.
Curtis noted that more than half of children clear the infection on their own by age 3, the age at which treatment can also begin. Treatment may also not be the right option for those who cannot swallow the medicine, which is available in oral pellets for children.
Greg Marchand, MD, an OB/GYN at the Marchand Institute for Minimally Invasive Surgery in Mesa, Arizona, said the research illuminates a “huge missed opportunity” to help children.
“If left untreated, these children risk serious liver complications like cirrhosis, liver cancer, high medical costs, and even death,” he said.
Marchand said clinicians must be aware of the guidelines for testing people who are pregnant and infants. In 2020, the US Centers for Disease Control and Prevention recommended universal HCV antibody screening during every pregnancy.
“There’s still hope that treatment rates will improve as both doctors and families become more familiar with” the newer drugs, he said.
No financial disclosures were reported.
The authors of this study were supported by various grants and awards, including from the National Institutes of Health, the James and Audrey Foster MGH Research Scholar Award, the Charles A. King Trust Postdoctoral Research Fellowship, and the Boston University Clinical and Translational Science Institute.
A version of this article appeared on Medscape.com.
Why Is Early-Onset CRC Rising? New Study Provides a Clue
The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.
While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?
A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.
What the Study Found
The new analysis found that
The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.
In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.
Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.
Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.
However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.
“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.
“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”
What the Study Means
Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.
Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”
Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”
“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”
Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”
However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.
But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.
If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.
There are also clinical implications if the findings pan out, Venook said.
This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”
The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.
A version of this article appeared on Medscape.com.
The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.
While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?
A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.
What the Study Found
The new analysis found that
The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.
In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.
Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.
Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.
However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.
“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.
“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”
What the Study Means
Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.
Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”
Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”
“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”
Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”
However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.
But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.
If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.
There are also clinical implications if the findings pan out, Venook said.
This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”
The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.
A version of this article appeared on Medscape.com.
The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.
While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?
A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.
What the Study Found
The new analysis found that
The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.
In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.
Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.
Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.
However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.
“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.
“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”
What the Study Means
Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.
Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”
Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”
“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”
Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”
However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.
But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.
If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.
There are also clinical implications if the findings pan out, Venook said.
This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”
The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.
A version of this article appeared on Medscape.com.
Semaglutide Therapy Improves Liver Histology in MASH
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
Histamine Pathway a Target for Erythropoietic Protoporphyria?
An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.
Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.
The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.
Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.
The Study
In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.
The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.
High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.
Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels.
Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.
Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers.
The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.
This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.
Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.
A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
Mutations in the ferrochelatase (FECH) gene cause erythropoietic porphyria. EPP is characterized biochemically by liver and bone marrow accumulation of protoporphyrin-IX (PP-IX), and is characterized clinically by hepatic dysfunction with progression in 1-4% to advanced liver disease.
A recent study by Kuo and colleagues exemplifies a bench-to-bedside evolution comprising pharmacological screening, mechanistic dissection, and ultimately translation of this mechanism to human subjects to treat EPP. They utilized high-throughput compound screening in a zebrafish model to identify the anti-histamine, chlorcyclizine (CCZ), as a candidate EPP therapy. Chlorciclizine lowered hepatocyte PP-IX in multiple EPP models by blocking peripheral histamine production, and by inducing hepatocyte PP-IX efflux. The data represent advances in the realms of both clinical therapeutics and molecular pathophysiological discovery.
From a discovery standpoint, strategic compound screening that utilizes the LOPAC (library of pharmaceutically active compounds) and Prestwick libraries offers at least two key characteristics. First, these compounds have largely known targets. The known pharmacology of chlorcyclizine provided immediate clues to validate mechanism rapidly in hepatic HPP, a relatively poorly understood disease. Moreover, screening libraries comprising FDA-approved drugs can minimize lag time between discovery and translation to interventional trials in human subjects.
Beyond such strategic discovery considerations, perhaps more exciting is the therapeutic potential for anti-histaminergic therapy to mitigate hepatic manifestations in EPP. Specifically, other porphyrias with hepatic complications have FDA-approved treatments, such as anti-ALAS1 siRNAs to treat acute hepatic porphyria (AHP). No such treatment currently exists for liver dysfunction in EPP, yet CCZ and other histamine-1 receptor blockers hold such promise. Indeed, the H1 inhibitor, cimetidine, is currently in an active phase 2 trial to treat EPP (NCT05020184).
Given the already widespread use of antihistamines to symptomatically treat cutaneous EPP, we may not be too distant from pivoting and deploying readily available H1Bs like cimetidine to treat EPP liver manifestations as well. Given recent data by Kuo and colleagues, such an outcome should not be too far-FECHed.
Brian DeBosch, MD, PhD, is Center Director of the nutrition & molecular metabolism research program, in the Division of Gastroenterology, Hepatology & Nutrition at Indiana University School of Medicine, Indianapolis. He declares no conflicts of interest.
Mutations in the ferrochelatase (FECH) gene cause erythropoietic porphyria. EPP is characterized biochemically by liver and bone marrow accumulation of protoporphyrin-IX (PP-IX), and is characterized clinically by hepatic dysfunction with progression in 1-4% to advanced liver disease.
A recent study by Kuo and colleagues exemplifies a bench-to-bedside evolution comprising pharmacological screening, mechanistic dissection, and ultimately translation of this mechanism to human subjects to treat EPP. They utilized high-throughput compound screening in a zebrafish model to identify the anti-histamine, chlorcyclizine (CCZ), as a candidate EPP therapy. Chlorciclizine lowered hepatocyte PP-IX in multiple EPP models by blocking peripheral histamine production, and by inducing hepatocyte PP-IX efflux. The data represent advances in the realms of both clinical therapeutics and molecular pathophysiological discovery.
From a discovery standpoint, strategic compound screening that utilizes the LOPAC (library of pharmaceutically active compounds) and Prestwick libraries offers at least two key characteristics. First, these compounds have largely known targets. The known pharmacology of chlorcyclizine provided immediate clues to validate mechanism rapidly in hepatic HPP, a relatively poorly understood disease. Moreover, screening libraries comprising FDA-approved drugs can minimize lag time between discovery and translation to interventional trials in human subjects.
Beyond such strategic discovery considerations, perhaps more exciting is the therapeutic potential for anti-histaminergic therapy to mitigate hepatic manifestations in EPP. Specifically, other porphyrias with hepatic complications have FDA-approved treatments, such as anti-ALAS1 siRNAs to treat acute hepatic porphyria (AHP). No such treatment currently exists for liver dysfunction in EPP, yet CCZ and other histamine-1 receptor blockers hold such promise. Indeed, the H1 inhibitor, cimetidine, is currently in an active phase 2 trial to treat EPP (NCT05020184).
Given the already widespread use of antihistamines to symptomatically treat cutaneous EPP, we may not be too distant from pivoting and deploying readily available H1Bs like cimetidine to treat EPP liver manifestations as well. Given recent data by Kuo and colleagues, such an outcome should not be too far-FECHed.
Brian DeBosch, MD, PhD, is Center Director of the nutrition & molecular metabolism research program, in the Division of Gastroenterology, Hepatology & Nutrition at Indiana University School of Medicine, Indianapolis. He declares no conflicts of interest.
Mutations in the ferrochelatase (FECH) gene cause erythropoietic porphyria. EPP is characterized biochemically by liver and bone marrow accumulation of protoporphyrin-IX (PP-IX), and is characterized clinically by hepatic dysfunction with progression in 1-4% to advanced liver disease.
A recent study by Kuo and colleagues exemplifies a bench-to-bedside evolution comprising pharmacological screening, mechanistic dissection, and ultimately translation of this mechanism to human subjects to treat EPP. They utilized high-throughput compound screening in a zebrafish model to identify the anti-histamine, chlorcyclizine (CCZ), as a candidate EPP therapy. Chlorciclizine lowered hepatocyte PP-IX in multiple EPP models by blocking peripheral histamine production, and by inducing hepatocyte PP-IX efflux. The data represent advances in the realms of both clinical therapeutics and molecular pathophysiological discovery.
From a discovery standpoint, strategic compound screening that utilizes the LOPAC (library of pharmaceutically active compounds) and Prestwick libraries offers at least two key characteristics. First, these compounds have largely known targets. The known pharmacology of chlorcyclizine provided immediate clues to validate mechanism rapidly in hepatic HPP, a relatively poorly understood disease. Moreover, screening libraries comprising FDA-approved drugs can minimize lag time between discovery and translation to interventional trials in human subjects.
Beyond such strategic discovery considerations, perhaps more exciting is the therapeutic potential for anti-histaminergic therapy to mitigate hepatic manifestations in EPP. Specifically, other porphyrias with hepatic complications have FDA-approved treatments, such as anti-ALAS1 siRNAs to treat acute hepatic porphyria (AHP). No such treatment currently exists for liver dysfunction in EPP, yet CCZ and other histamine-1 receptor blockers hold such promise. Indeed, the H1 inhibitor, cimetidine, is currently in an active phase 2 trial to treat EPP (NCT05020184).
Given the already widespread use of antihistamines to symptomatically treat cutaneous EPP, we may not be too distant from pivoting and deploying readily available H1Bs like cimetidine to treat EPP liver manifestations as well. Given recent data by Kuo and colleagues, such an outcome should not be too far-FECHed.
Brian DeBosch, MD, PhD, is Center Director of the nutrition & molecular metabolism research program, in the Division of Gastroenterology, Hepatology & Nutrition at Indiana University School of Medicine, Indianapolis. He declares no conflicts of interest.
An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.
Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.
The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.
Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.
The Study
In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.
The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.
High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.
Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels.
Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.
Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers.
The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.
This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.
Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.
A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.
Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.
The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.
Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.
The Study
In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.
The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.
High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.
Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels.
Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.
Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers.
The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.
This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.
Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.
A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
From Cellular and Molecular Gastroenterology and Hepatology