Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may...Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may be useful in diagnosing NASH,but results across studies have been inconsistent.We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease(NAFLD),and in all patients,circulating CK-18 M30 levels were measured.Individuals with a NAFLD activity score(NAS)≥5 with a score of≥1 for each of steatosis,ballooning,and lobular inflammation were diagnosed as having definite NASH;individuals with a NAS≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver(NAFL).Results:A total of 2571 participants were screened,and 1008(153 with NAFL and 855 with NASH)were finally enrolled.Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL(mean difference 177 U/L;standardized mean difference[SMD]:0.87[0.69–1.04]).There was an interaction between CK-18 M30 levels and serum alanine aminotransferase,body mass index(BMI),and hypertension(P<0.001,P=0.026 and P=0.049,respectively).CK-18 M30 levels were positively associated with histological NAS in most centers.The area under the receiver operating characteristics(AUROC)for NASH was 0.750(95%confidence intervals:0.714–0.787),and CK-18 M30 at Youden’s index maximum was 275.7 U/L.Both sensitivity(55%[52%–59%])and positive predictive value(59%)were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)has become one of the most prevalent chronic liver diseases worldwide,bringing risk of multiorgan disfunctions including cardiovascular events,complications o...Metabolic dysfunction-associated fatty liver disease(MAFLD)has become one of the most prevalent chronic liver diseases worldwide,bringing risk of multiorgan disfunctions including cardiovascular events,complications of cirrhosis,and even malignance.In terms of health burden management,screening patients with high risk of MAFLD and providing individual comprehensive treatment is critical.Although there are numerous agents entering clinical trials for MAFLD treatment every year,there is still no effective approved drug.The nomenclature of MAFLD highlighted the concomitant metabolic disorders and obesity.MAFLD patients with type 2 diabetes had higher risk of developing liver cirrhosis and cancer,and would benefit from anti-hyperglycemic agents;overweight and obese patients may benefit more from weight loss therapies;for patients with metabolic syndrome,individual comprehensive management is needed to reduce the risk of adverse outcomes.In this review,we introduced the current status and advances of the treatment of MAFLD based on weight loss,improving insulin resistance,and management of cardiometabolic disorders,in order to provide individualized therapy approaches for patients with MAFLD.展开更多
The increasing burden of non-alcoholic fatty liver disease:Non-alcoholic fatty liver disease(NAFLD)is the_most common causeofchronicliverdisease in the world.NAFLD encompasses,a spectrum of liver,disease,ranging from ...The increasing burden of non-alcoholic fatty liver disease:Non-alcoholic fatty liver disease(NAFLD)is the_most common causeofchronicliverdisease in the world.NAFLD encompasses,a spectrum of liver,disease,ranging from simple hepatic steatosis to non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma(HCC).展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82070588)High-Level Creative Talents from the Department of Public Health in Zhejiang Province(No.S2032102600032)+4 种基金Project of New Century 551 Talent Nurturing in Wenzhou.G.Targher is supported in part by grants from the University School of Medicine of Verona,Verona,ItalyC.D.Byrne is supported in part by the Southampton NIHR Biomedical Research Centre(No.IS-BRC-20004),UK.MEJG are supported by the Robert W.Storr Bequest to the Sydney Medical Foundation,University of Sydneya National Health and Medical Research Council of Australia(NHMRC)Program Grant(No.APP1053206)Project and ideas grants(Nos.APP2001692,APP1107178,and APP1108422).
文摘Background:Liver biopsy for the diagnosis of non-alcoholic steatohepatitis(NASH)is limited by its inherent invasiveness and possible sampling errors.Some studies have shown that cytokeratin-18(CK-18)concentrations may be useful in diagnosing NASH,but results across studies have been inconsistent.We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.Methods:Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease(NAFLD),and in all patients,circulating CK-18 M30 levels were measured.Individuals with a NAFLD activity score(NAS)≥5 with a score of≥1 for each of steatosis,ballooning,and lobular inflammation were diagnosed as having definite NASH;individuals with a NAS≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver(NAFL).Results:A total of 2571 participants were screened,and 1008(153 with NAFL and 855 with NASH)were finally enrolled.Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL(mean difference 177 U/L;standardized mean difference[SMD]:0.87[0.69–1.04]).There was an interaction between CK-18 M30 levels and serum alanine aminotransferase,body mass index(BMI),and hypertension(P<0.001,P=0.026 and P=0.049,respectively).CK-18 M30 levels were positively associated with histological NAS in most centers.The area under the receiver operating characteristics(AUROC)for NASH was 0.750(95%confidence intervals:0.714–0.787),and CK-18 M30 at Youden’s index maximum was 275.7 U/L.Both sensitivity(55%[52%–59%])and positive predictive value(59%)were not ideal.Conclusion:This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
基金National Natural Science Foundation of China(Nos.81873565,81900507,82170593)Collaborative Innovation Program of Shanghai Municipal Health Commission(No.2020CXJQ01)+2 种基金Shanghai Leading Talent Plan 2017Star Program of Shanghai Jiao Tong University(No.YG2021QN54)Hospital Funded Clinical Research,Clinical Research Unit,Xinhua Hospital,Affiliated to Shanghai Jiao Tong University School of Medicine(No.17CSK04)。
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)has become one of the most prevalent chronic liver diseases worldwide,bringing risk of multiorgan disfunctions including cardiovascular events,complications of cirrhosis,and even malignance.In terms of health burden management,screening patients with high risk of MAFLD and providing individual comprehensive treatment is critical.Although there are numerous agents entering clinical trials for MAFLD treatment every year,there is still no effective approved drug.The nomenclature of MAFLD highlighted the concomitant metabolic disorders and obesity.MAFLD patients with type 2 diabetes had higher risk of developing liver cirrhosis and cancer,and would benefit from anti-hyperglycemic agents;overweight and obese patients may benefit more from weight loss therapies;for patients with metabolic syndrome,individual comprehensive management is needed to reduce the risk of adverse outcomes.In this review,we introduced the current status and advances of the treatment of MAFLD based on weight loss,improving insulin resistance,and management of cardiometabolic disorders,in order to provide individualized therapy approaches for patients with MAFLD.
基金This study was supported by grants from the National Key Research and Development Program of China(No. 2021YFC2700802)the National Natural Science Foundation of China(Nos. 81900507 and 82170593)。
文摘The increasing burden of non-alcoholic fatty liver disease:Non-alcoholic fatty liver disease(NAFLD)is the_most common causeofchronicliverdisease in the world.NAFLD encompasses,a spectrum of liver,disease,ranging from simple hepatic steatosis to non-alcoholic steatohepatitis(NASH),fibrosis,cirrhosis,and hepatocellular carcinoma(HCC).
