Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with live...Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.展开更多
Background:Despite the clear link between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus,little is understood about how glycemic control impacts histological severity.We aimed to investigate the d...Background:Despite the clear link between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus,little is understood about how glycemic control impacts histological severity.We aimed to investigate the deeper association between hemoglobin A1c(HbA1c)and the histologic severity of liver fibrosis.Methods:A total of 568 adults with biopsy-proven NAFLD from the PERSONS cohort in Wenzhou were enrolled.The association between mean HbA1c and hepatic histological features was investigated with ordinal logistic regression.Generalized additive models were used to identify the non-linear relationship between HbA1c and increased fibrosis stage(stage F3).Causal mediation analysis was performed to calculate the indirect effect of the relationship between HbA1c and hepatic fibrosis mediated by cytokines.Results:Every 1%increase in mean HbA1c was associated with 16%higher odds of increased fibrosis stage(odds ratio 1.16,95%CI 1.04–1.30),even after adjustment for confounding factors.There was a non-linear association between HbA1c and increased fibrosis stage(stage F3),and the HbA1c inflection point was 9.2%.In particular,the ORs on the left and right sides of this inflection point were 2.1(95%CI 1.4–3.3)and 0.1(95%CI 0–4.8),respectively.7%of the association(OR 1.07,95%CI 1.01–1.12)between HbA1c and liver fibrosis was mediated by leukemia inhibitory factor.Conclusions:Glycemic control predicts severity of hepatic fibrosis and leukemia inhibitory factor plays an intermediary role between them,and thus optimizing glycemic control may be a means of modifying the risk of fibrosis progression in NAFLD.展开更多
Nonalcoholic fatty liver disease(NAFLD)has become the most common cause of liver disease in many parts of the world,causing considerable liver-related(steatohepatitis,cirrhosis,liver failure and hepatocellular carcino...Nonalcoholic fatty liver disease(NAFLD)has become the most common cause of liver disease in many parts of the world,causing considerable liver-related(steatohepatitis,cirrhosis,liver failure and hepatocellular carcinoma)and extra-hepatic morbidity and mortality(mainly cardiovascular disease,chronic kidney disease or certain types of extra-hepatic cancers).Recently,based on insights gained from the past two decades,an international panel of experts from 22 countries has taken the initiative to propose a new name and definition for NAFLD in adult individuals-that is,metabolic dysfunction-associated fatty liver disease.This proposed change in nomenclature is not simply a semantic revision,but may facilitate improved diagnosis of this common liver disease for health promotion,case identification,patient awareness,ongoing clinical trials and health services delivery.The aim of this commentary is to discuss the proposal for a change in nomenclature of this common and burdensome liver disease and to address the“pros and cons”for changing the name according to the perspective of different stakeholders.展开更多
Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic C...Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.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
Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).Howev...Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).However,no studies have examined the effect of interactions between these three genotypes to affect liver disease severity.We assessed the effect of these three SNPs on nonalcoholic steatohepatitis(NASH)and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.Methods:We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD.Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409.Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction(GMDR)analysis.Results:The mean±standard deviation age of these 415 patients was 41.3±12.5 years,and 75.9%were men.Patients with SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH,even after adjustment for age,sex and body mass index.GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH.Additionally,the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C.Conclusions:NAFLD patients carrying the SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH.These three SNPs may synergistically interact to increase susceptibility to NASH.展开更多
Background and Aims:Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3(PNPLA3)rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver diseas...Background and Aims:Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3(PNPLA3)rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease(NAFLD).We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism.Methods:The variant of PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD.Visceral fat area(VFA)was measured by bioelectrical impedance.Significant liver fibrosis(SF),defined as stage F≥2 on histology,was the outcome measure of interest.Results:The distribution of PNPLA3 genotypes was CC:27.5%,CG:48.2%,and GG:24.3%.Higher VFA was associated with greater risk of having SF(adjusted-odds ratio[OR]:1.03;95%confidence interval[CI]:1.02–1.04,p<0.05),independent of potential confounders.Among subjects with the same VFA level,the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not.Stratified analysis showed that PNPLA3 rs738409 significantly influenced the association between VFA and SF.VFA remained significantly associated with SF only among the rs738409 G-allele carriers(adjusted-OR:1.05;95%CI:1.03–1.08 for the GG group;and adjusted-OR:1.03;95%CI:1.01–1.04 for the GC group).There was a significant interaction between VFA and PNPLA3 rs738409 genotype(Pinteraction=0.004).Conclusions:PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD.Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF。展开更多
Background:Animal organ meat(offal)is a food with high nutrient density that is popular in different parts of the world,but its relationship with nonalcoholic steatohepatitis(NASH)is unclear.We aimed to examine whethe...Background:Animal organ meat(offal)is a food with high nutrient density that is popular in different parts of the world,but its relationship with nonalcoholic steatohepatitis(NASH)is unclear.We aimed to examine whether daily animal organ meat consumption is associated with the presence of NASH in individuals with nonalcoholic fatty liver disease(NAFLD).Methods:A total of 136 Chinese adults with biopsy-proven NAFLD were included.Definite NASH was defined as NAFLD activity score≥4 and at least one point for steatosis,ballooning,and lobular inflammation.Daily animal organ meat consumption was estimated using a self-administered validated food frequency questionnaire.Logistic regression analysis was performed to assess the association between animal organ meat intake and liver disease severity.Results:The 136 participants(80.9%men)of the study had a mean±standard deviation(SD)age of 39.0±12.5 years and body mass index of 27.4±3.6 kg/m2.Prevalence of definite NASH was 65.4%.Daily median organ meat consumption was 1.30 g/1,000 kcal.Animal organ meat consumption was inversely associated with the presence of NASH even after adjustment of demographics,lifestyle variables,metabolic and dietary factors,as well as liver fibrosis stage;adjusted-odds ratios(95%confidence intervals)for NASH were 0.15(0.03,0.69)for the highest tertile and 0.18(0.05,0.70)for the medium tertile,compared to the lowest(reference)tertile of animal organ meat intake(P value for trend=0.024).Conclusions:Our results suggest for the first time that higher animal organ meat consumption is associated with a lower prevalence of NASH in Chinese individuals with biopsy-proven NAFLD.展开更多
Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide.NAFLD‐related cirrhosis is often complicated by portal hypertension(PHT).Recent evidence showed that portal venous pr...Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide.NAFLD‐related cirrhosis is often complicated by portal hypertension(PHT).Recent evidence showed that portal venous pressure(PVP)starts to rise in the early stages of NAFLD,even in absence of advanced fibrosis or cirrhosis.However,the precise pathological mechanisms of this process are still poorly understood.Lipid accumulation,hepatocellular ballooning,sinusoidal endothelial cell dysfunction,capillarization,microthrombosis,increased angiogenesis,and pericellular fibrosis may all be involved in the early development of increased PVP in NAFLD.Direct measurement of PHT is invasive and impractical in noncirrhotic NAFLD individuals and may also underestimate its severity.Thus,the development and validation of noninvasive and more accurate measurements,including new serum biomarkers,scoring models,and imaging techniques(such as ultrasonography,elastography,and magnetic resonance imaging),are urgently needed.Owing to the increasing morbidity,challenges in the prevention and management of PHT in NAFLD are unprecedented.This review article aims to briefly discuss these challenges and summarizes the mechanisms,diagnosis,and emerging therapies for PHT in people with NAFLD.展开更多
基金Supported by(in part)the Southampton National Institute for Health Research Biomedical Research Centre(Byrne CD)grants from the School of Medicine of the Verona University(Targher GT)
文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications.
基金This work was supported by a grant from the National Natural Sci-ence Foundation of China(82070588)a High Level Creative Talents grant from the Department of Public Health in Zhejiang Province(S2032102600032)+1 种基金a grant from the 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:Despite the clear link between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus,little is understood about how glycemic control impacts histological severity.We aimed to investigate the deeper association between hemoglobin A1c(HbA1c)and the histologic severity of liver fibrosis.Methods:A total of 568 adults with biopsy-proven NAFLD from the PERSONS cohort in Wenzhou were enrolled.The association between mean HbA1c and hepatic histological features was investigated with ordinal logistic regression.Generalized additive models were used to identify the non-linear relationship between HbA1c and increased fibrosis stage(stage F3).Causal mediation analysis was performed to calculate the indirect effect of the relationship between HbA1c and hepatic fibrosis mediated by cytokines.Results:Every 1%increase in mean HbA1c was associated with 16%higher odds of increased fibrosis stage(odds ratio 1.16,95%CI 1.04–1.30),even after adjustment for confounding factors.There was a non-linear association between HbA1c and increased fibrosis stage(stage F3),and the HbA1c inflection point was 9.2%.In particular,the ORs on the left and right sides of this inflection point were 2.1(95%CI 1.4–3.3)and 0.1(95%CI 0–4.8),respectively.7%of the association(OR 1.07,95%CI 1.01–1.12)between HbA1c and liver fibrosis was mediated by leukemia inhibitory factor.Conclusions:Glycemic control predicts severity of hepatic fibrosis and leukemia inhibitory factor plays an intermediary role between them,and thus optimizing glycemic control may be a means of modifying the risk of fibrosis progression in NAFLD.
文摘Nonalcoholic fatty liver disease(NAFLD)has become the most common cause of liver disease in many parts of the world,causing considerable liver-related(steatohepatitis,cirrhosis,liver failure and hepatocellular carcinoma)and extra-hepatic morbidity and mortality(mainly cardiovascular disease,chronic kidney disease or certain types of extra-hepatic cancers).Recently,based on insights gained from the past two decades,an international panel of experts from 22 countries has taken the initiative to propose a new name and definition for NAFLD in adult individuals-that is,metabolic dysfunction-associated fatty liver disease.This proposed change in nomenclature is not simply a semantic revision,but may facilitate improved diagnosis of this common liver disease for health promotion,case identification,patient awareness,ongoing clinical trials and health services delivery.The aim of this commentary is to discuss the proposal for a change in nomenclature of this common and burdensome liver disease and to address the“pros and cons”for changing the name according to the perspective of different stakeholders.
基金This work was 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)+3 种基金Project of New Century 551 Talent Nurturing in Wenzhou.GT was supported in part by grants from the University School of Medicine of Verona(Verona,Italy)CDB was supported in part by the Southampton NIHR Biomedical Research Centre(ISBRC-20004)UK.ME and JG were supported by the Robert W.Storr Bequest to the Sydney Medical Foundation,University of Sydney(Sydney,Australia)and the National Health and Medical Research Council of Australia(NHMRC)Program(APP1053206,APP1149976)Project(APP1107178 and APP1108422)grants.
文摘Background and Aims:In Europeans,variants in the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene impact liver histology in metabolic-associated fatty liver disease(MAFLD).The impact of these variants in ethnic Chinese is unknown.The aim of this study was to investigate the potential associations in Chinese patients.Methods:In total,427 Han Chinese with biopsy-confirmed MAFLD were enrolled.Two single nucleotide polymorphisms in HSD17B13 were genotyped:rs72613567 and rs6531975.Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.Results:In our cohort,the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis[odds ratio(OR):2.93(1.20–7.17),p=0.019 for the additive model;OR:3.32(1.39–7.91),p=0.007 for the recessive model],representing an inverse association as compared to the results from European cohorts.In contrast,we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant[OR:0.48(0.24–0.98),p=0.043 for the additive model;OR:0.62(0.40–0.94),p=0.025 for the dominant model].HSD17B13 variants were only associated with fibrosis but no other histological features.Furthermore,HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.Conclusions:HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans.These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.
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 grants from the National Natural Science Foundation of China(82070588)the High Level Creative Talents from Department of Public Health in Zhejiang Proince(S2032102600032)+2 种基金Project of New Century 551 Talent Nurturing in WenzhouGT was supported in part by grants from the School of Medicine,University of Verona,Verona,ItalyCDB was supported in part by the Southampton NIHR Biomedical Research Centre(IS-BRC-20004),UK.
文摘Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).However,no studies have examined the effect of interactions between these three genotypes to affect liver disease severity.We assessed the effect of these three SNPs on nonalcoholic steatohepatitis(NASH)and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.Methods:We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD.Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409.Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction(GMDR)analysis.Results:The mean±standard deviation age of these 415 patients was 41.3±12.5 years,and 75.9%were men.Patients with SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH,even after adjustment for age,sex and body mass index.GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH.Additionally,the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C.Conclusions:NAFLD patients carrying the SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH.These three SNPs may synergistically interact to increase susceptibility to NASH.
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)the Project of New Century 551 Talent Nurturing in Wenzhou.GT was supported in part by grants from the University School of Medicine of Verona,Verona,Italy.CDB was supported in part by the Southampton NIHR Biomedical Research Centre(ISBRC-20004),UK.
文摘Background and Aims:Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3(PNPLA3)rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease(NAFLD).We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism.Methods:The variant of PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD.Visceral fat area(VFA)was measured by bioelectrical impedance.Significant liver fibrosis(SF),defined as stage F≥2 on histology,was the outcome measure of interest.Results:The distribution of PNPLA3 genotypes was CC:27.5%,CG:48.2%,and GG:24.3%.Higher VFA was associated with greater risk of having SF(adjusted-odds ratio[OR]:1.03;95%confidence interval[CI]:1.02–1.04,p<0.05),independent of potential confounders.Among subjects with the same VFA level,the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not.Stratified analysis showed that PNPLA3 rs738409 significantly influenced the association between VFA and SF.VFA remained significantly associated with SF only among the rs738409 G-allele carriers(adjusted-OR:1.05;95%CI:1.03–1.08 for the GG group;and adjusted-OR:1.03;95%CI:1.01–1.04 for the GC group).There was a significant interaction between VFA and PNPLA3 rs738409 genotype(Pinteraction=0.004).Conclusions:PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD.Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF。
基金supported by grants from the National Natural Science Foundation of China(No.82070588)High Level Creative Talents from Department of Public Health in Zhejiang Province(No.S2032102600032)+1 种基金Project of New Century 551 Talent Nurturing in Wenzhou,Wenzhou Science and Technology Bureau(No.Y20190530)the University School of Medicine of Verona in Italy to GT and in part by the Southampton NIHR Biomedical Research Centre in UK(No.IS-BRC-20004 to CDB).
文摘Background:Animal organ meat(offal)is a food with high nutrient density that is popular in different parts of the world,but its relationship with nonalcoholic steatohepatitis(NASH)is unclear.We aimed to examine whether daily animal organ meat consumption is associated with the presence of NASH in individuals with nonalcoholic fatty liver disease(NAFLD).Methods:A total of 136 Chinese adults with biopsy-proven NAFLD were included.Definite NASH was defined as NAFLD activity score≥4 and at least one point for steatosis,ballooning,and lobular inflammation.Daily animal organ meat consumption was estimated using a self-administered validated food frequency questionnaire.Logistic regression analysis was performed to assess the association between animal organ meat intake and liver disease severity.Results:The 136 participants(80.9%men)of the study had a mean±standard deviation(SD)age of 39.0±12.5 years and body mass index of 27.4±3.6 kg/m2.Prevalence of definite NASH was 65.4%.Daily median organ meat consumption was 1.30 g/1,000 kcal.Animal organ meat consumption was inversely associated with the presence of NASH even after adjustment of demographics,lifestyle variables,metabolic and dietary factors,as well as liver fibrosis stage;adjusted-odds ratios(95%confidence intervals)for NASH were 0.15(0.03,0.69)for the highest tertile and 0.18(0.05,0.70)for the medium tertile,compared to the lowest(reference)tertile of animal organ meat intake(P value for trend=0.024).Conclusions:Our results suggest for the first time that higher animal organ meat consumption is associated with a lower prevalence of NASH in Chinese individuals with biopsy-proven NAFLD.
基金National Natural Science Foundation of China,Grant/Award Number:82070588Agenzia Italiana del Farmaco,Ministero della Salute,Grant/Award Number:RF‐2016‐02364358。
文摘Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide.NAFLD‐related cirrhosis is often complicated by portal hypertension(PHT).Recent evidence showed that portal venous pressure(PVP)starts to rise in the early stages of NAFLD,even in absence of advanced fibrosis or cirrhosis.However,the precise pathological mechanisms of this process are still poorly understood.Lipid accumulation,hepatocellular ballooning,sinusoidal endothelial cell dysfunction,capillarization,microthrombosis,increased angiogenesis,and pericellular fibrosis may all be involved in the early development of increased PVP in NAFLD.Direct measurement of PHT is invasive and impractical in noncirrhotic NAFLD individuals and may also underestimate its severity.Thus,the development and validation of noninvasive and more accurate measurements,including new serum biomarkers,scoring models,and imaging techniques(such as ultrasonography,elastography,and magnetic resonance imaging),are urgently needed.Owing to the increasing morbidity,challenges in the prevention and management of PHT in NAFLD are unprecedented.This review article aims to briefly discuss these challenges and summarizes the mechanisms,diagnosis,and emerging therapies for PHT in people with NAFLD.
