Metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),has emerged as a leading cause of chronic liver disease globally,reflecting the convergence ...Metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),has emerged as a leading cause of chronic liver disease globally,reflecting the convergence of rising obesity,insulin resistance,and type 2 diabetes mellitus(1).The disease burden is not only liver-related but systemic,contributing to increased cardiovascular risk,malignancy,and reduced quality of life(2).The clinical spectrum of MASLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),fibrosis,and cirrhosis,with a growing share of hepatocellular carcinoma cases now being attributed to MASLD rather than viral etiologies(3).MASLD pathophysiology involves a complex interplay of chronic low-grade inflammation,immune cell activation,and systemic metabolic dysfunction,implicating organs beyond the liver,including adipose tissue and spleen(2,3).展开更多
The prevalence of cirrhosis and hepatocellular carcinoma resulting from metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing,posing a significant burden on both the economy and public health(1,...The prevalence of cirrhosis and hepatocellular carcinoma resulting from metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing,posing a significant burden on both the economy and public health(1,2).Although the need for effective therapeutic strategies for MASLD is growing,pharmacologic options remain limited,with resmetirom currently the only approved drug.Consequently,lifestyle modification-particularly weight reduction through diet and exercise-remains the cornerstone of MASLD management.展开更多
Background:High liver fat content(LFC)induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease(MASLD),while maintaining a significant decline in ...Background:High liver fat content(LFC)induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease(MASLD),while maintaining a significant decline in magnetic resonance imaging-based proton density fat fraction(MRI-PDFF)(≥30%decline relative to baseline)without worsening fibrosis results in improved histological severity and prognosis.However,the factors associated with the loss of sustained responses to treatment remain unclear,and we aim to identify them.Methods:Consecutive treatment-naïve MASLD patients between January 2015 and February 2022,with follow-up until April 2023,were included in this prospective cohort study.LFC quantified by MRI-PDFF and liver stiffness measurements(LSM)determined by two-dimensional shear wave elastography(2D-SWE)were evaluated at weeks 0,24 and 48.MRI-PDFF response was defined as a≥30%relative decline in PDFF values,and LSM response was defined as a≥1 stage decline from baseline.Results:A total of 602 MASLD patients were enrolled.Of the 303 patients with a 24-week MRI-PDFF response and complete follow-up of 48 weeks,the rate of loss of MRI-PDFF response was 29.4%,and multivariable logistic regression analyses showed that 24-week insulin resistance(IR),still regular exercise and caloric restriction after 24 weeks,and the relative decline in LFC were risk factors for loss of MRI-PDFF response.Loss of LSM response at 48 weeks occurred in 15.9%of patients,and multivariable analysis confirmed 24-week serum total bile acid(TBA)levels and the relative decline in TBA from baseline as independent predictors.No significant association was found at 48 weeks between loss of MRI-PDFF response and loss of LSM response.Conclusions:MASLD patients with IR and high TBA levels are at higher risks of subsequent diminished sustained improvements of steatosis and fibrosis,respectively.展开更多
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),has emerged as a leading cause of chronic liver disease globally,reflecting the convergence of rising obesity,insulin resistance,and type 2 diabetes mellitus(1).The disease burden is not only liver-related but systemic,contributing to increased cardiovascular risk,malignancy,and reduced quality of life(2).The clinical spectrum of MASLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),fibrosis,and cirrhosis,with a growing share of hepatocellular carcinoma cases now being attributed to MASLD rather than viral etiologies(3).MASLD pathophysiology involves a complex interplay of chronic low-grade inflammation,immune cell activation,and systemic metabolic dysfunction,implicating organs beyond the liver,including adipose tissue and spleen(2,3).
基金supported by Japan Agency for Medical Research and Development(JP25fk0210123 to M.K.)Japanese Ministry of Health,Labour and Welfare(23HC2001 to M.K.)+1 种基金from Japan Agency for Medical Research and Development(JP25fk0310535,JP25fk0210174,and JP25fk0210123 to N.T.)Japanese Ministry of Health,Labour and Welfare(23HC2003 and 23HC2002 to N.T.).
文摘The prevalence of cirrhosis and hepatocellular carcinoma resulting from metabolic dysfunction-associated steatotic liver disease(MASLD)is increasing,posing a significant burden on both the economy and public health(1,2).Although the need for effective therapeutic strategies for MASLD is growing,pharmacologic options remain limited,with resmetirom currently the only approved drug.Consequently,lifestyle modification-particularly weight reduction through diet and exercise-remains the cornerstone of MASLD management.
基金National Natural Science Foundation of China(grant Nos.81870404 and 82100648)Natural Science Foundation of Guangdong Province,China(grant Nos.2021A1515011442 and 2022A1515012369)China Postdoctoral Science Foundation(grant No.2020M683128).
文摘Background:High liver fat content(LFC)induces increased risks of both hepatic and extrahepatic progression in metabolic dysfunction-associated steatotic liver disease(MASLD),while maintaining a significant decline in magnetic resonance imaging-based proton density fat fraction(MRI-PDFF)(≥30%decline relative to baseline)without worsening fibrosis results in improved histological severity and prognosis.However,the factors associated with the loss of sustained responses to treatment remain unclear,and we aim to identify them.Methods:Consecutive treatment-naïve MASLD patients between January 2015 and February 2022,with follow-up until April 2023,were included in this prospective cohort study.LFC quantified by MRI-PDFF and liver stiffness measurements(LSM)determined by two-dimensional shear wave elastography(2D-SWE)were evaluated at weeks 0,24 and 48.MRI-PDFF response was defined as a≥30%relative decline in PDFF values,and LSM response was defined as a≥1 stage decline from baseline.Results:A total of 602 MASLD patients were enrolled.Of the 303 patients with a 24-week MRI-PDFF response and complete follow-up of 48 weeks,the rate of loss of MRI-PDFF response was 29.4%,and multivariable logistic regression analyses showed that 24-week insulin resistance(IR),still regular exercise and caloric restriction after 24 weeks,and the relative decline in LFC were risk factors for loss of MRI-PDFF response.Loss of LSM response at 48 weeks occurred in 15.9%of patients,and multivariable analysis confirmed 24-week serum total bile acid(TBA)levels and the relative decline in TBA from baseline as independent predictors.No significant association was found at 48 weeks between loss of MRI-PDFF response and loss of LSM response.Conclusions:MASLD patients with IR and high TBA levels are at higher risks of subsequent diminished sustained improvements of steatosis and fibrosis,respectively.
