Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment ...Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.展开更多
In this editorial,we comment on the article by Chen et al.Metabolic dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and obesity....In this editorial,we comment on the article by Chen et al.Metabolic dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and obesity.Given its detri-mental health impact,early identification of at-risk individuals is crucial.MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic dysregulation.However,in large-scale epidemiological studies,liver biopsies are not feasible.The application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized software.Blood biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical.Analysis of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods.Accordingly,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.展开更多
BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs...BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk factors.METHODS A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter score.Subjects were recruited from two tertiary hospitals.Genetic alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3B,FDFT1,COL13A1,EFCAB4B,PZP,and TM6SF2 were genotyped using the TaqMan®Predesigned SNP Genotyping Assay.RESULTS Weight and body mass index(BMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,P<0.001 and 26.9 kg,95%CI:23-40.8 vs 23.3 kg 95%CI:19-27.6,P<0.001 respectively).The prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(P<0.001).PNPLA3 GG was more likely to be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),BMI(OR:1.295%CI:1.1-1.4,P<0.001)and PNPLA3 GG(OR:3.495%CI:1.3-9.2,P=0.014)were associated with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFT1,COL13A1,PZP,and TM6SF2 are not significantly associated.Hypertriglyceridemia,high BMI,and PNPLA3 GG are independent predictors of MAFLD.展开更多
Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of p...Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of paradigms.With improved outcomes post-transplantation,LT is no longer merely life saving,but has the potential to also significantly improve quality of life.This review summarizes the clinical presentation,medical treatment and indications for LT for some of the common LBMDs.We also provide a practical update on the dilemmas and controversies surrounding the indications for transplantation,surgical considerations and prognosis and long terms outcomes for pediatric LT in LBMDs.Important progress has been made in understanding these diseases in recent years and with that we outline some of the new therapies that have emerged.展开更多
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most commonchronic liver cell damage worldwide. It is strongly associated with an increasedrisk of cardiovascular disease (CVD). There are not enough recomme...Nonalcoholic fatty liver disease (NAFLD) has emerged as the most commonchronic liver cell damage worldwide. It is strongly associated with an increasedrisk of cardiovascular disease (CVD). There are not enough recommendations forscreening subjects with nonalcoholic steatohepatitis cirrhosis, who are notcandidates for liver transplantation, nor who are asymptomatic with NAFLDwithout cirrhosis. In the current comprehensive narrative review, we aimed toevaluate the associations between CVD and NAFLD. Distinguishing themechanisms linking these two disorders offers the opportunity to developtargeted therapies. Moreover, we will discuss screening approaches (whom andhow-to) and treatment modalities proposed to reduce cardiovascular risk inpatients with NAFLD.展开更多
目的探讨串联质谱(tandem mass spectrometry,MS/MS)联合气相质谱(gas phase mass spectrometry,GC-MS)在新生儿重症监护病房(neonatal intensive care unit,NICU)遗传代谢病(inherited metabolic disorders,IMD)筛查诊断中的应用价值...目的探讨串联质谱(tandem mass spectrometry,MS/MS)联合气相质谱(gas phase mass spectrometry,GC-MS)在新生儿重症监护病房(neonatal intensive care unit,NICU)遗传代谢病(inherited metabolic disorders,IMD)筛查诊断中的应用价值。方法选取2020年1月至2021年12月解放军总医院第七医学中心NICU收治的3682例新生儿(其中足月儿1794例,早产儿1888例)为观察对象,采集干血斑行MS/MS遗传代谢病筛查。初次筛查阳性者重新采样复查并行尿液GC-MS检测。根据患儿代谢谱结合临床表现进行生化诊断。统计学方法采用χ^(2)检验。结果3682例NICU患儿中初筛阳性率为5.65%(208/3682),复筛阳性率为1.33%(49/3682),共生化诊断IMD患儿14例,总检出率为0.38%(14/3682),其中足月儿检出率高于早产儿[0.67%(12/1794)与0.11%(2/1888),χ^(2)=7.697,P=0.006]。14例IMD中,有机酸代谢异常11例,包括甲基丙二酸血症8例(57.1%)、戊二酸血症2例(14.3%)、3-甲基戊二烯酸尿症1例(7.1%);氨基酸代谢异常3例,包括尿素循环障碍2例(14.3%)、高苯丙氨酸血症1例(7.1%)。MS/MS初筛假阳性率为5.29%(194/3668),阳性预测值为6.73%(14/208)。召回复查后,二次MS/MS复测,假阳性率为0.95%(35/3668),阳性预测值为28.57%(14/49)。在各类MS/MS指标异常中,丙酰肉碱及其比值增高、戊二酰肉碱增高的阳性预测值高于氨基酸类代谢异常。结论NICU人群IMD发病率较高,且存在早产、感染等多种非遗传因素,干扰MS/MS代谢筛查结果。及时进行MS/MS复查及尿GC-MS分析可以提高诊断效率,明确生化诊断。展开更多
Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAF...Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAFLD between different items.We also aimed to investigate the associations between advanced fibrosis and risk factors.Methods:This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community.Patients were stratified following MAFLD diagnostic criteria,to group A(395 patients)for type 2 diabetes,group B(1,818 patients)for body mass index(BMI)>23 kg/m^(2),and group C(44 patients)for BMI≤23kg/m^(2) with at least two metabolic factors.Advanced fibrosis was defined as a fibrosis-4 index>2.67.Results:Between 2009 and 2020,1,948 MAFLD patients were recruited,including 478 with concomitant liver diseases.Advanced fibrosis was observed in 125 patients.A significantly larger proportion of patients in group C(25.0%)than in group A(7.6%)and group B(5.8%)had advanced fibrosis (p<0.01).Logistic regression analysis found that hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfection(odds ratio[OR]:12.14,95%confidence interval[CI]:4.04-36.52;p<0.01),HCV infection(OR:7.87,95%CI:4.78-12.97;p<0.01),group C(OR:6.00,95%CI:2.53-14.22;p<0.01),and TC/LDL-C(OR:1.21,95%CI:1.06-1.38;p<0.01)were significant predictors of advanced fibrosis.Conclusions:A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis.HCV infection was significantly associated with advanced fibrosis.展开更多
In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to...In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably including"lean NAFLD"has recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.展开更多
Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited dis...Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.展开更多
基金the National Natural Science Foundation of China,No.82070588 and No.82370577.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.
基金Supported by National Natural Science Foundation of China,No.81873541.
文摘In this editorial,we comment on the article by Chen et al.Metabolic dysfunction-associated fatty liver disease(MAFLD)is a global public health burden whose incidence has risen concurrently with overweight and obesity.Given its detri-mental health impact,early identification of at-risk individuals is crucial.MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy,imaging,or blood biomarkers,and one of the following conditions:Overweight/obesity,type 2 diabetes mellitus,or metabolic dysregulation.However,in large-scale epidemiological studies,liver biopsies are not feasible.The application of techniques such as ultrasonography,computed tomography,magnetic resonance imaging,and magnetic resonance spectroscopy is restricted by their limited sensitivity,low effectiveness,high costs,and need for specialized software.Blood biomarkers offer several advantages,particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical.Analysis of cumulative effects of excess high-normal blood alanine aminotrans-ferase(ALT)levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods.Accordingly,investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring,enabling timely inter-vention and management and improving patient outcomes.
文摘BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk factors.METHODS A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter score.Subjects were recruited from two tertiary hospitals.Genetic alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3B,FDFT1,COL13A1,EFCAB4B,PZP,and TM6SF2 were genotyped using the TaqMan®Predesigned SNP Genotyping Assay.RESULTS Weight and body mass index(BMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,P<0.001 and 26.9 kg,95%CI:23-40.8 vs 23.3 kg 95%CI:19-27.6,P<0.001 respectively).The prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(P<0.001).PNPLA3 GG was more likely to be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),BMI(OR:1.295%CI:1.1-1.4,P<0.001)and PNPLA3 GG(OR:3.495%CI:1.3-9.2,P=0.014)were associated with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFT1,COL13A1,PZP,and TM6SF2 are not significantly associated.Hypertriglyceridemia,high BMI,and PNPLA3 GG are independent predictors of MAFLD.
文摘Liver transplantation(LT)remains the gold standard treatment for end stage liver disease in the pediatric population.For liver based metabolic disorders(LBMDs),the decision for LT is predicated on a different set of paradigms.With improved outcomes post-transplantation,LT is no longer merely life saving,but has the potential to also significantly improve quality of life.This review summarizes the clinical presentation,medical treatment and indications for LT for some of the common LBMDs.We also provide a practical update on the dilemmas and controversies surrounding the indications for transplantation,surgical considerations and prognosis and long terms outcomes for pediatric LT in LBMDs.Important progress has been made in understanding these diseases in recent years and with that we outline some of the new therapies that have emerged.
文摘Nonalcoholic fatty liver disease (NAFLD) has emerged as the most commonchronic liver cell damage worldwide. It is strongly associated with an increasedrisk of cardiovascular disease (CVD). There are not enough recommendations forscreening subjects with nonalcoholic steatohepatitis cirrhosis, who are notcandidates for liver transplantation, nor who are asymptomatic with NAFLDwithout cirrhosis. In the current comprehensive narrative review, we aimed toevaluate the associations between CVD and NAFLD. Distinguishing themechanisms linking these two disorders offers the opportunity to developtargeted therapies. Moreover, we will discuss screening approaches (whom andhow-to) and treatment modalities proposed to reduce cardiovascular risk inpatients with NAFLD.
文摘目的探讨串联质谱(tandem mass spectrometry,MS/MS)联合气相质谱(gas phase mass spectrometry,GC-MS)在新生儿重症监护病房(neonatal intensive care unit,NICU)遗传代谢病(inherited metabolic disorders,IMD)筛查诊断中的应用价值。方法选取2020年1月至2021年12月解放军总医院第七医学中心NICU收治的3682例新生儿(其中足月儿1794例,早产儿1888例)为观察对象,采集干血斑行MS/MS遗传代谢病筛查。初次筛查阳性者重新采样复查并行尿液GC-MS检测。根据患儿代谢谱结合临床表现进行生化诊断。统计学方法采用χ^(2)检验。结果3682例NICU患儿中初筛阳性率为5.65%(208/3682),复筛阳性率为1.33%(49/3682),共生化诊断IMD患儿14例,总检出率为0.38%(14/3682),其中足月儿检出率高于早产儿[0.67%(12/1794)与0.11%(2/1888),χ^(2)=7.697,P=0.006]。14例IMD中,有机酸代谢异常11例,包括甲基丙二酸血症8例(57.1%)、戊二酸血症2例(14.3%)、3-甲基戊二烯酸尿症1例(7.1%);氨基酸代谢异常3例,包括尿素循环障碍2例(14.3%)、高苯丙氨酸血症1例(7.1%)。MS/MS初筛假阳性率为5.29%(194/3668),阳性预测值为6.73%(14/208)。召回复查后,二次MS/MS复测,假阳性率为0.95%(35/3668),阳性预测值为28.57%(14/49)。在各类MS/MS指标异常中,丙酰肉碱及其比值增高、戊二酰肉碱增高的阳性预测值高于氨基酸类代谢异常。结论NICU人群IMD发病率较高,且存在早产、感染等多种非遗传因素,干扰MS/MS代谢筛查结果。及时进行MS/MS复查及尿GC-MS分析可以提高诊断效率,明确生化诊断。
基金supported in part by grants from The Ministry of Science and Technology,Taiwan(MOST 110-2314-B-03-073-MY3)The Ministry of Health and Welfare,Taiwan(MOHW,112-TDU-B-221-124007)+1 种基金National Yang Ming Chiao Tung University-Kaohsiung Medical University Joint Research Project(NYCU-KMU-111-I001,NYCU-KMU-112-I001)Kaohsiung Medical University Hospital(KMUH SA10907,KMUH110-0R05).
文摘Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAFLD between different items.We also aimed to investigate the associations between advanced fibrosis and risk factors.Methods:This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community.Patients were stratified following MAFLD diagnostic criteria,to group A(395 patients)for type 2 diabetes,group B(1,818 patients)for body mass index(BMI)>23 kg/m^(2),and group C(44 patients)for BMI≤23kg/m^(2) with at least two metabolic factors.Advanced fibrosis was defined as a fibrosis-4 index>2.67.Results:Between 2009 and 2020,1,948 MAFLD patients were recruited,including 478 with concomitant liver diseases.Advanced fibrosis was observed in 125 patients.A significantly larger proportion of patients in group C(25.0%)than in group A(7.6%)and group B(5.8%)had advanced fibrosis (p<0.01).Logistic regression analysis found that hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfection(odds ratio[OR]:12.14,95%confidence interval[CI]:4.04-36.52;p<0.01),HCV infection(OR:7.87,95%CI:4.78-12.97;p<0.01),group C(OR:6.00,95%CI:2.53-14.22;p<0.01),and TC/LDL-C(OR:1.21,95%CI:1.06-1.38;p<0.01)were significant predictors of advanced fibrosis.Conclusions:A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis.HCV infection was significantly associated with advanced fibrosis.
文摘In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably including"lean NAFLD"has recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.
文摘Inborn errors of metabolism (IEM) include a broad spectrum of defects of various gene products that affect interme-diary metabolism in the body. Studying the molecular and biochemical mechanisms of those inherited disorder, systematically summarizing the disease phenotype and natural history, providing diagnostic rationale and methodology and treatment strategy comprise the context of human biochemical genetics. This session focused on: (1) manifestations of representative metabolic disorders; (2) the emergent technology and application of newborn screening of metabolic disorders using tandem mass spec-trometry; (3) principles of managing IEM; (4) the concept of carrier testing aiming prevention. Early detection of patients with IEM allows early intervention and more options for treatment.
