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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