A new expression for contact deformation is given, and the normal contact stiff- ness between single asperities is derived according to Hooke＇s law. A contact model between two ellipsoidal asperities is simulated by ...A new expression for contact deformation is given, and the normal contact stiff- ness between single asperities is derived according to Hooke＇s law. A contact model between two ellipsoidal asperities is simulated by the FE method, the result compared with the theoretical solution. It is found that the curves of the normal contact stiffness versus the included angle in the principal curvature direction show similar trends and evolve as a cosine feature. The effects of the parameters on normal contact stiffness are found to show that normal contact stiffness increases and reaches the upper limit gradually with an increase in these parameters.展开更多
Aims:The synergistic impact of alcohol consumption and cardiometabolic risk factors(CMRFs)on liver health remains unclear.Herein,we aimed to investigate the interplay between varying levels of alcohol consumption and ...Aims:The synergistic impact of alcohol consumption and cardiometabolic risk factors(CMRFs)on liver health remains unclear.Herein,we aimed to investigate the interplay between varying levels of alcohol consumption and the number of CMRFs on all-cause mortality in individuals with metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic and alcohol-associated liver disease(MetALD).Methods:Adult participants with ultrasound-proven hepatic steatosis were identified using the Third National Health and Nutrition Examination Survey(NHANES III)database.Multivariate Cox regression was applied to investigate the association between incremental alcohol consumption and the number of CMRFs,with all-cause mortality as the outcome.The E-value was calculated to assess the robustness of the associations,and additive interaction models were used to explore the synergistic effects of alcohol consumption and CMRFs on mortality.Results:A total of 2161 individuals(1957 with MASLD and 204 with MetALD)between the Years 1988 and 1994 were included in the analysis.During a follow-up period of 51,719 person-years,the overall mortality rate was 1.46%per person-year.Stratification by age showed an increased mortality risk associated with CMRFs and alcohol consumption in individuals aged<65 years,especially among those with 3-5 CMRFs(hazard ratio:3.15-5.71,all p<0.05).Additive interaction models also supported a synergistic effect in this subgroup,while no such trend was observed in those aged≥65 years.Conclusion:Among individuals with MASLD/MetALD and MASLD alone,a significant synergistic effect between alcohol consumption and CMRFs on mortality risk was found in those aged<65 years.This suggests an age-stratified approach for managing modifiable risk factors in individuals with MASLD or MetALD.展开更多
Chronic hepatitis B(CHB)virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments.In recent years,as the prevalence of obesity and metabolic syn...Chronic hepatitis B(CHB)virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments.In recent years,as the prevalence of obesity and metabolic syndrome has increased,non-alcoholic fatty liver disease(NAFLD)in patients with CHB has become more common.Both diseases can lead to liver fibrosis and even hepatocellular carcinoma,but the risk of dual etiology,outcome,and CHB combined with NAFLD is not fully elucidated.In this review,we assess the overlapping prevalence of NAFLD and CHB,summarize recent studies of clinical and basic research related to potential interactions,and evaluate the progressive changes of treatments for CHB patients with NAFLD.This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection,and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.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
Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 20...Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.展开更多
The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and funct...The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and functional integrity is crucial to human health.Intestinal mucus is regulated by factors such as diet,living habits,hormones,neurotransmitters,cytokines,and intestinal flora.The mucus layer’s thickness,viscosity,porosity,growth rate,and glycosylation status affect the structure of the gut flora colonized on it.The interaction between"mucus layer-soil"and"gut bacteria-seed"is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Probiotics,prebiotics,fecal microbiota transplantation(FMT),and wash microbial transplantation are efficient methods for managing NAFLD,but their long-term efficacy is poor.FMT is focused on achieving the goal of treating diseases by enhancing the"gut bacteria-seed".However,a lack of effective repair and management of the"mucus layer-soil"may be a reason why"seeds"cannot be well colonized and grow in the host gut,as the thinning and destruction of the"mucus layer-soil"is an early symptom of NAFLD.This review summarizes the existing correlation between intestinal mucus and gut microbiota,as well as the pathogenesis of NAFLD,and proposes a new perspective that"mucus layer-soil"restoration combined with"gut bacteria-seed"FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.展开更多
Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fu...Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fully clarified.Methods:A total of 165 HCC patients,including 146 males and 19 females,were enrolled.The median age was 55 years(range,27-78 years).Corresponding clinical and pathological information was collected for further analysis.A total of 168 tumor tissues from these patients were selected for next-generation sequencing(NGS)-based 450 panel gene sequencing.Genomic alterations including single nucleotide variations(SNV),short and long insertions and deletions(InDels),copy number variations,and gene rearrangements were analyzed.Tumor mutational burden(TMB)was measured by an algorithm developed in-house.The top quartile of HCC was classified as TMB high.Results:A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues.TMB values were identified in 160 HCC specimens,with a median TMB of 5.4 Muts/Mb(range,0-28.4 Muts/Mb)and a 75%TMB of 7.7 Muts/Mb.The most commonly mutated genes were TP53,TERT,CTNNB1,AXIN1,RB1,TSC2,CCND1,ARID1A,and FGF19.SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs.Compared to wild-type patients,the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients(P<0.05).The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients(P<0.05).The proportion of Edmondson grade I-II,alpha fetoprotein(AFP)<25μmg/L,and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients(P<0.05).CTNNB1 mutations were associated with TMB high in HCC patients(P<0.05).Based on correlation analysis,the mutation of TP53 was independently correlated with microvascular invasion(P=0.002,OR=3.096)and Edmondson grade III-IV(P=0.008,OR=2.613).The mutation of TERT was independently correlated with tumor invasion of the liver capsule(P=0.001,OR=3.030),and the mutation of CTNNB1 was independently correlated with AFP(<25μmg/L)(P=0.009,OR=3.414).Conclusions:The most frequently mutated genes of HCC patients in China were TP53,TERT,and CTNNB1,which mainly lead to the occurrence and development of HCC by regulating the P53 pathway,Wnt pathway,and telomere repair pathway.There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients,while in CTNNB1 mutated patients,there were more patients with Edmondson I-II grade,AFP<25μmg/L,and a non-hepatitis B background.Also,the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.展开更多
Background:Currently,there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy.T2-weighted images(T2WI)are routinely obtained fr...Background:Currently,there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy.T2-weighted images(T2WI)are routinely obtained from liver magnetic resonance imaging(MRI)scan sequences.We aimed to establish a radiomics signature based on T2WI(T2-RS)for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease(NAFLD).Methods:A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this study.The hepatic inflammatory activity score(IAS)was calculated by the unweighted sum of the histologic scores for lobular inflammation and ballooning.One thousand and thirty-two radiomics features were extracted from the localized region of interest(ROI)in the right liver lobe of T2WI and,subsequently,selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator(LASSO)methods.The T2-RS was calculated by adding the selected features weighted by their coefficients.Results:Eighteen radiomics features from Laplacian of Gaussian,wavelet,and original images were selected for establishing T2-RS.The T2-RS value differed significantly between groups with increasing grades of hepatic inflammation(P<0.01).The T2-RS yielded an area under the receiver operating characteristic(ROC)curve(AUROC)of 0.80[95%confidence interval(CI):0.71-0.89]for predicting hepatic inflammation in the training cohort with excellent calibration.The AUROCs of T2-RS in the internal cohort and external validation cohorts were 0.77(0.61-0.93)and 0.75(0.63-0.84),respectively.Conclusions:The T2-RS derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.展开更多
In recent years,with the increasing incidence of obesity and other metabolic diseases,the prevalence of non-alcoholic fatty liver disease(NAFLD)has increased and it has become a major health problem affecting more tha...In recent years,with the increasing incidence of obesity and other metabolic diseases,the prevalence of non-alcoholic fatty liver disease(NAFLD)has increased and it has become a major health problem affecting more than one quarter of the world’s population.Recently,experts reached a consensus that NAFLD does not reflect the current knowledge,and metabolic dysfunctionassociated fatty liver disease(MAFLD)was suggested as a more appropriate term.MAFLD is not just a simple renaming of NAFLD.The definition of MAFLD allows a patient to have dual(or more)etiologies for their liver disease,which will help to exclude more heterogeneous patients.In this review,we introduce the significant differences between the definitions of NAFLD and MAFLD.In addition,we also describe the advantages of the term MAFLD in the pathophysiology,therapy,and patient management.展开更多
Background and aims:Tenofovir disoproxil fumarate(TDF)is the first-line therapy for chronic hepatitis B.This interim analysis presents the efficacy and safety data for TDF at Week 144 in patients with chronic hepatiti...Background and aims:Tenofovir disoproxil fumarate(TDF)is the first-line therapy for chronic hepatitis B.This interim analysis presents the efficacy and safety data for TDF at Week 144 in patients with chronic hepatitis B and advanced fibrosis or compensated cirrhosis from China.Methods:Patients were assessed for incidence of newly diagnosed hepatocellular carcinoma(HCC)and disease progression,liver stiffness measurement(LSM),virological suppression(serum hepatitis B virus DNA<20 IU/mL),alanine aminotransferase normalization,hepatitis B e antigen(HBeAg)loss and seroconversion,histological liver fibrosis score,and safety at Week 144.Results:Overall,197 patients were enrolled.At Week 144,the incidence of newly diagnosed HCC was observed in 2.1%patients,and the incidence of disease progression was observed in 3.6%patients.The mean(standard deviation)change in LSM from baseline was5.1(5.85)kPa.Serum hepatitis B virus DNA<20 IU/mL was observed in 94.1%patients,alanine aminotransferase normalization in 33.5%patients,HBeAg loss in 35.6%patients,and HBeAg seroconversion in 14.4%patients.Among patients with stage F3 or F4 fibrosis at baseline by LSM,38.3%patients regressed to stage F0/1,and 22.0%of patients regressed to stage F2 at Week 144.Overall,67.7%patients experienced≥1 adverse events,13.8%patients experienced TDF-related adverse events,and 16.4%patients experienced serious(none were TDF-related).Conclusions:At Week 144 of TDF treatment,low incidence of HCC and disease progression were reported.Virological suppression was observed in 94.1%patients,which was associated with fibrosis regression.No new safety events were identified.展开更多
Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were...Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were collected from 163 participants who next received two doses of an inactivated COvVID-19 vaccine(CoronaVac)at a 28-day interval.Using TMT-based proteomics,we identified 1,715 serum and 7,342 peripheral blood mononuclear cells(PBMCs)proteins.We proposed two sets of potential biomarkers(seven from serum,five from PBMCs)at baseline using machine learning,and predicted the individual seropositivity 57 days after vaccination(AUC=0.87).Based on the four PBMC's potential biomarkers,we predicted the antibody persistence until 180 days after vaccination(AUC=0.79).Our data highlighted characteristic hematological host responses,including altered lymphocyte migration regulation,neutrophil degranulation,and humoral immune response.This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after coVID-19 vaccination,shedding light on immunization mechanisms and individual booster shot planning.展开更多
Citation of this article:Xu X,Rui F,Ni W,Wu C,Shi J,Li J.A Novel Algorithm for Streamlining Diagnosis of Advanced Liver Fibrosis in CHB Patients with Concurrent Hepatic Steatosis.J Clin Transl Hepatol 2024;12(2):222–...Citation of this article:Xu X,Rui F,Ni W,Wu C,Shi J,Li J.A Novel Algorithm for Streamlining Diagnosis of Advanced Liver Fibrosis in CHB Patients with Concurrent Hepatic Steatosis.J Clin Transl Hepatol 2024;12(2):222–226.doi:10.14218/JCTH.2023.00362.Chronic hepatitis B(CHB)with concurrent hepatic steatosis(HS)is a growing challenge for public health globally.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD),is increasingly prevalent in Asia,1 an area also endemic for chronic hepatitis B(CHB).Our prev...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD),is increasingly prevalent in Asia,1 an area also endemic for chronic hepatitis B(CHB).Our previous study showed that the coexistence of CHB and hepatic steatosis(HS)has reached 36.5%in Asia,2 with a similar figure observed globally.3 This coexistence may exacerbate the progression of hepatic fibrosis.展开更多
基金Project supported by the National Basic Research Program of China(973 Program)(No.2009CB724406)
文摘A new expression for contact deformation is given, and the normal contact stiff- ness between single asperities is derived according to Hooke＇s law. A contact model between two ellipsoidal asperities is simulated by the FE method, the result compared with the theoretical solution. It is found that the curves of the normal contact stiffness versus the included angle in the principal curvature direction show similar trends and evolve as a cosine feature. The effects of the parameters on normal contact stiffness are found to show that normal contact stiffness increases and reaches the upper limit gradually with an increase in these parameters.
基金supported by the National Natural Science Foundation of China(No.82170609)NSFC-RGC Forum for Young Scholars(No.82411560273)+1 种基金Nanjing Drum Tower Hospital Academic Innovation Peak Project(No.2024-DF-03)the Natural Science Foundation of Jiangsu Province(No.BK20231118).
文摘Aims:The synergistic impact of alcohol consumption and cardiometabolic risk factors(CMRFs)on liver health remains unclear.Herein,we aimed to investigate the interplay between varying levels of alcohol consumption and the number of CMRFs on all-cause mortality in individuals with metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic and alcohol-associated liver disease(MetALD).Methods:Adult participants with ultrasound-proven hepatic steatosis were identified using the Third National Health and Nutrition Examination Survey(NHANES III)database.Multivariate Cox regression was applied to investigate the association between incremental alcohol consumption and the number of CMRFs,with all-cause mortality as the outcome.The E-value was calculated to assess the robustness of the associations,and additive interaction models were used to explore the synergistic effects of alcohol consumption and CMRFs on mortality.Results:A total of 2161 individuals(1957 with MASLD and 204 with MetALD)between the Years 1988 and 1994 were included in the analysis.During a follow-up period of 51,719 person-years,the overall mortality rate was 1.46%per person-year.Stratification by age showed an increased mortality risk associated with CMRFs and alcohol consumption in individuals aged<65 years,especially among those with 3-5 CMRFs(hazard ratio:3.15-5.71,all p<0.05).Additive interaction models also supported a synergistic effect in this subgroup,while no such trend was observed in those aged≥65 years.Conclusion:Among individuals with MASLD/MetALD and MASLD alone,a significant synergistic effect between alcohol consumption and CMRFs on mortality risk was found in those aged<65 years.This suggests an age-stratified approach for managing modifiable risk factors in individuals with MASLD or MetALD.
基金supported by grants from the National Natural Science Fund(Nos.81970545,82170609)the Natural Science Foundation of Shandong Province(Major Project)(No.ZR2020KH006)+1 种基金the Ji’nan Science and Technology Development Project(No.202019079)the Nanjing Medical Science and Technique Development Foundation(No.YKK20058).
文摘Chronic hepatitis B(CHB)virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments.In recent years,as the prevalence of obesity and metabolic syndrome has increased,non-alcoholic fatty liver disease(NAFLD)in patients with CHB has become more common.Both diseases can lead to liver fibrosis and even hepatocellular carcinoma,but the risk of dual etiology,outcome,and CHB combined with NAFLD is not fully elucidated.In this review,we assess the overlapping prevalence of NAFLD and CHB,summarize recent studies of clinical and basic research related to potential interactions,and evaluate the progressive changes of treatments for CHB patients with NAFLD.This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection,and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.
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Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.
基金National Natural Science Funds of China(Nos.82204827,81970545,and 82170609)Zhejiang Provincial Basic Public Welfare Research Project(Nos.LQ23H270016 and LGF20H030010)+1 种基金Hangzhou Major Science and Technology Plan Project(No.20172016A02)Major Projects of Hangzhou Medical and Health Science and Technology Plan(No.0020191059)
文摘The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells,as well as acts as the"mucus layer-soil"for intestinal flora adhesion and colonization.Its structural and functional integrity is crucial to human health.Intestinal mucus is regulated by factors such as diet,living habits,hormones,neurotransmitters,cytokines,and intestinal flora.The mucus layer’s thickness,viscosity,porosity,growth rate,and glycosylation status affect the structure of the gut flora colonized on it.The interaction between"mucus layer-soil"and"gut bacteria-seed"is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease(NAFLD).Probiotics,prebiotics,fecal microbiota transplantation(FMT),and wash microbial transplantation are efficient methods for managing NAFLD,but their long-term efficacy is poor.FMT is focused on achieving the goal of treating diseases by enhancing the"gut bacteria-seed".However,a lack of effective repair and management of the"mucus layer-soil"may be a reason why"seeds"cannot be well colonized and grow in the host gut,as the thinning and destruction of the"mucus layer-soil"is an early symptom of NAFLD.This review summarizes the existing correlation between intestinal mucus and gut microbiota,as well as the pathogenesis of NAFLD,and proposes a new perspective that"mucus layer-soil"restoration combined with"gut bacteria-seed"FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.
文摘Background:Hepatocellular carcinoma(HCC)is one of the most common causes of cancer worldwide.Although many studies have focused on oncogene characteristics,the genomic landscape of Chinese HCC patients has not been fully clarified.Methods:A total of 165 HCC patients,including 146 males and 19 females,were enrolled.The median age was 55 years(range,27-78 years).Corresponding clinical and pathological information was collected for further analysis.A total of 168 tumor tissues from these patients were selected for next-generation sequencing(NGS)-based 450 panel gene sequencing.Genomic alterations including single nucleotide variations(SNV),short and long insertions and deletions(InDels),copy number variations,and gene rearrangements were analyzed.Tumor mutational burden(TMB)was measured by an algorithm developed in-house.The top quartile of HCC was classified as TMB high.Results:A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues.TMB values were identified in 160 HCC specimens,with a median TMB of 5.4 Muts/Mb(range,0-28.4 Muts/Mb)and a 75%TMB of 7.7 Muts/Mb.The most commonly mutated genes were TP53,TERT,CTNNB1,AXIN1,RB1,TSC2,CCND1,ARID1A,and FGF19.SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs.Compared to wild-type patients,the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in TP53 mutated patients(P<0.05).The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients(P<0.05).The proportion of Edmondson grade I-II,alpha fetoprotein(AFP)<25μmg/L,and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients(P<0.05).CTNNB1 mutations were associated with TMB high in HCC patients(P<0.05).Based on correlation analysis,the mutation of TP53 was independently correlated with microvascular invasion(P=0.002,OR=3.096)and Edmondson grade III-IV(P=0.008,OR=2.613).The mutation of TERT was independently correlated with tumor invasion of the liver capsule(P=0.001,OR=3.030),and the mutation of CTNNB1 was independently correlated with AFP(<25μmg/L)(P=0.009,OR=3.414).Conclusions:The most frequently mutated genes of HCC patients in China were TP53,TERT,and CTNNB1,which mainly lead to the occurrence and development of HCC by regulating the P53 pathway,Wnt pathway,and telomere repair pathway.There were more patients with microvascular invasion and Edmondson III-IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients,while in CTNNB1 mutated patients,there were more patients with Edmondson I-II grade,AFP<25μmg/L,and a non-hepatitis B background.Also,the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.
基金supported by grants from the National Natural Science Foundation of China(82070588)High Level Creative Talents from Department of Public Health in Zhejiang Province(S2032102600032)+1 种基金Project of New Century 551 Talent Nurturing in Wenzhou.GT is supported in part by grants from the University School of Medicine of Verona,Verona,ItalyCDB is supported in part by the Southampton NIHR Biomedical Research Centre(IS-BRC-20004),UK.
文摘Background:Currently,there are no effective methods for assessing hepatic inflammation without resorting to histological examination of liver tissue obtained by biopsy.T2-weighted images(T2WI)are routinely obtained from liver magnetic resonance imaging(MRI)scan sequences.We aimed to establish a radiomics signature based on T2WI(T2-RS)for assessment of hepatic inflammation in people with nonalcoholic fatty liver disease(NAFLD).Methods:A total of 203 individuals with biopsy-confirmed NAFLD from two independent Chinese cohorts with liver MRI examination were enrolled in this study.The hepatic inflammatory activity score(IAS)was calculated by the unweighted sum of the histologic scores for lobular inflammation and ballooning.One thousand and thirty-two radiomics features were extracted from the localized region of interest(ROI)in the right liver lobe of T2WI and,subsequently,selected by minimum redundancy maximum relevance and least absolute shrinkage and selection operator(LASSO)methods.The T2-RS was calculated by adding the selected features weighted by their coefficients.Results:Eighteen radiomics features from Laplacian of Gaussian,wavelet,and original images were selected for establishing T2-RS.The T2-RS value differed significantly between groups with increasing grades of hepatic inflammation(P<0.01).The T2-RS yielded an area under the receiver operating characteristic(ROC)curve(AUROC)of 0.80[95%confidence interval(CI):0.71-0.89]for predicting hepatic inflammation in the training cohort with excellent calibration.The AUROCs of T2-RS in the internal cohort and external validation cohorts were 0.77(0.61-0.93)and 0.75(0.63-0.84),respectively.Conclusions:The T2-RS derived from radiomics analysis of T2WI shows promising utility for predicting hepatic inflammation in individuals with NAFLD.
基金supported by the National Natural Science Fund(No.81970545,82170609)Natural Science Foundation of Shandong Province(Major Project)(No.ZR2020KH006)Ji’nan Science and Technology Development Project(No.2020190790).
文摘In recent years,with the increasing incidence of obesity and other metabolic diseases,the prevalence of non-alcoholic fatty liver disease(NAFLD)has increased and it has become a major health problem affecting more than one quarter of the world’s population.Recently,experts reached a consensus that NAFLD does not reflect the current knowledge,and metabolic dysfunctionassociated fatty liver disease(MAFLD)was suggested as a more appropriate term.MAFLD is not just a simple renaming of NAFLD.The definition of MAFLD allows a patient to have dual(or more)etiologies for their liver disease,which will help to exclude more heterogeneous patients.In this review,we introduce the significant differences between the definitions of NAFLD and MAFLD.In addition,we also describe the advantages of the term MAFLD in the pathophysiology,therapy,and patient management.
基金supported by GlaxoSmithKline(China)R&D Company Limited.
文摘Background and aims:Tenofovir disoproxil fumarate(TDF)is the first-line therapy for chronic hepatitis B.This interim analysis presents the efficacy and safety data for TDF at Week 144 in patients with chronic hepatitis B and advanced fibrosis or compensated cirrhosis from China.Methods:Patients were assessed for incidence of newly diagnosed hepatocellular carcinoma(HCC)and disease progression,liver stiffness measurement(LSM),virological suppression(serum hepatitis B virus DNA<20 IU/mL),alanine aminotransferase normalization,hepatitis B e antigen(HBeAg)loss and seroconversion,histological liver fibrosis score,and safety at Week 144.Results:Overall,197 patients were enrolled.At Week 144,the incidence of newly diagnosed HCC was observed in 2.1%patients,and the incidence of disease progression was observed in 3.6%patients.The mean(standard deviation)change in LSM from baseline was5.1(5.85)kPa.Serum hepatitis B virus DNA<20 IU/mL was observed in 94.1%patients,alanine aminotransferase normalization in 33.5%patients,HBeAg loss in 35.6%patients,and HBeAg seroconversion in 14.4%patients.Among patients with stage F3 or F4 fibrosis at baseline by LSM,38.3%patients regressed to stage F0/1,and 22.0%of patients regressed to stage F2 at Week 144.Overall,67.7%patients experienced≥1 adverse events,13.8%patients experienced TDF-related adverse events,and 16.4%patients experienced serious(none were TDF-related).Conclusions:At Week 144 of TDF treatment,low incidence of HCC and disease progression were reported.Virological suppression was observed in 94.1%patients,which was associated with fibrosis regression.No new safety events were identified.
基金supported by the National Natural Science Foundation of China(32200763)Key medical disciplines of Hangzhou,the Medical Health Science and Technology Project of Hangzhou municipal Health Commission(A20210205)+1 种基金the National Key R&D Program of China(2020YFE0202200)Funding for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University(2022-LCYJ-MS-08).
文摘Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were collected from 163 participants who next received two doses of an inactivated COvVID-19 vaccine(CoronaVac)at a 28-day interval.Using TMT-based proteomics,we identified 1,715 serum and 7,342 peripheral blood mononuclear cells(PBMCs)proteins.We proposed two sets of potential biomarkers(seven from serum,five from PBMCs)at baseline using machine learning,and predicted the individual seropositivity 57 days after vaccination(AUC=0.87).Based on the four PBMC's potential biomarkers,we predicted the antibody persistence until 180 days after vaccination(AUC=0.79).Our data highlighted characteristic hematological host responses,including altered lymphocyte migration regulation,neutrophil degranulation,and humoral immune response.This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after coVID-19 vaccination,shedding light on immunization mechanisms and individual booster shot planning.
文摘Citation of this article:Xu X,Rui F,Ni W,Wu C,Shi J,Li J.A Novel Algorithm for Streamlining Diagnosis of Advanced Liver Fibrosis in CHB Patients with Concurrent Hepatic Steatosis.J Clin Transl Hepatol 2024;12(2):222–226.doi:10.14218/JCTH.2023.00362.Chronic hepatitis B(CHB)with concurrent hepatic steatosis(HS)is a growing challenge for public health globally.
基金supported by the National Natural Science Fund(No.82170609,81970545)the Natural Science Foundation of Shandong Province(Major Project)(No.ZR2020KH006)+2 种基金LX was supported by the Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-059B)the Tianjin Health Science and Technology Project key discipline special(TJWJ2022XK034)the 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Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as non-alcoholic fatty liver disease(NAFLD),is increasingly prevalent in Asia,1 an area also endemic for chronic hepatitis B(CHB).Our previous study showed that the coexistence of CHB and hepatic steatosis(HS)has reached 36.5%in Asia,2 with a similar figure observed globally.3 This coexistence may exacerbate the progression of hepatic fibrosis.
