Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related...Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.展开更多
Non-alcoholic fatty liver disease(NAFLD)has become the world’s largest chronic liver disease in the 21st century,affecting 20%-30%of the world’s population.As the epidemiology,etiology,and pathogenesis of NAFLD have...Non-alcoholic fatty liver disease(NAFLD)has become the world’s largest chronic liver disease in the 21st century,affecting 20%-30%of the world’s population.As the epidemiology,etiology,and pathogenesis of NAFLD have been studied in-depth,it has been gradually recognized that most patients with NAFLD have one or more combined metabolic abnormalities known as metabolic syndrome.In 2020,the international expert group changed the name of NAFLD to metabolic-associated fatty liver disease(MAFLD)and proposed new diagnostic criteria for MAFLD and MAFLD-related liver cirrhosis,as well as the conceptual framework of other cause-related fatty liver diseases to avoid diagnosis based on the exclusion of other causes and better reflect its pathogenesis.However,there are still many ambiguities in the term,and changing the name does not address the unmet key needs in the field.The change from NAFLD to MAFLD was not just a change of definition.The problems and challenges are summarized as follows:epidemiology,children,rationality of"metabolism,"diagnostic criteria,double/multiple causes,drug discovery,clinical trials,and awareness raising.Metabolic-associated fatty liver disease has complex disease characteristics,and there are still some problems that need to be solved.展开更多
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
End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decom...End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decompensation.Consequently,infections are among the most common complications of disease progression.There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus.This consensus assembled up-to-date knowledge and experience across Chinese colleagues,providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 62375202)Natural Science Foundation of Tianjin (Grant No. 23JCYBJC00950)+2 种基金Tianjin Health Science and Technology Project Key Discipline Special (Grant No. TJWJ2022XK034)Tianjin Key Medical Discipline (Specialty) Construction Project (Grant No.TJYXZDXK-059B)Research Project in Key Areas of TCM in 2024 (Grant No. 2024022)
文摘Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.
基金Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-059B)Tianjin Health Science and Technology Project key discipline special(TJWJ2022XK034)Research Project of Chinese Traditional Medicine and Chinese Traditional Medicine Combined with Western Medicine of Tianjin Municipal Health and Family Planning Commission(2021022)。
文摘Non-alcoholic fatty liver disease(NAFLD)has become the world’s largest chronic liver disease in the 21st century,affecting 20%-30%of the world’s population.As the epidemiology,etiology,and pathogenesis of NAFLD have been studied in-depth,it has been gradually recognized that most patients with NAFLD have one or more combined metabolic abnormalities known as metabolic syndrome.In 2020,the international expert group changed the name of NAFLD to metabolic-associated fatty liver disease(MAFLD)and proposed new diagnostic criteria for MAFLD and MAFLD-related liver cirrhosis,as well as the conceptual framework of other cause-related fatty liver diseases to avoid diagnosis based on the exclusion of other causes and better reflect its pathogenesis.However,there are still many ambiguities in the term,and changing the name does not address the unmet key needs in the field.The change from NAFLD to MAFLD was not just a change of definition.The problems and challenges are summarized as follows:epidemiology,children,rationality of"metabolism,"diagnostic criteria,double/multiple causes,drug discovery,clinical trials,and awareness raising.Metabolic-associated fatty liver disease has complex disease characteristics,and there are still some problems that need to be solved.
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.
文摘End-stage liver disease(ESLD)is a life-threatening clinical syndrome that markedly increases mortality in patients with infections.In patients with ESLD,infections can induce or aggravate the occurrence of liver decompensation.Consequently,infections are among the most common complications of disease progression.There is a lack of working procedure for early diagnosis and appropriate management for patients with ESLD complicated by infections as well as local and international guidelines or consensus.This consensus assembled up-to-date knowledge and experience across Chinese colleagues,providing data on principles as well as working procedures for the diagnosis and treatment of patients with ESLD complicated by infections.
