BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic diseases in the world.Nowadays,the percentage of non-obese or lean patients with NAFLD is increasing.NAFLD in non-obese populations,e...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic diseases in the world.Nowadays,the percentage of non-obese or lean patients with NAFLD is increasing.NAFLD in non-obese populations,especially the lean subgroup with a normal waist circumference(WC),might lead to more problems than obese individuals,as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD.If the precise characteristics of these populations,especially the lean subgroup,are identified,the clinicians would be able to provide more appropriate advice and treatment to these populations.AIM To investigate the prevalence,clinical characteristics,risk factors,and possible indicators for NAFLD in lean Chinese adults with a normal WC.METHODS People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included.Their fatty liver index(FLI),abdominal ultrasonography results,and controlled attenuation parameter were all assessed.Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls.RESULTS A total of 2715 subjects who underwent routine health examinations were included in the study.Among 810 lean participants with a normal WC,142(17.5%)fulfilled the diagnostic criteria for NAFLD.Waist-height ratio,hemoglobin,platelets,and triglycerides were significant factors associated with the presence of NAFLD in these participants.The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15,which had a 77.8%sensitivity and 75.9%specificity.There was no significant difference in the single-nucleotide polymorphisms in the SIRT1,APOC3,PNPLA3,AGTR1,and PPARGC1A genes between lean subjects with and without NAFLD(P<0.05).CONCLUSION NAFLD is not uncommon in lean Chinese adults even with a normal WC.Metabolic factors,rather than genetic factors,may play important roles in the development of NAFLD in this population.A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC.展开更多
With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiolo...With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully characterized.In this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such patients.We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation.For CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses.The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.展开更多
Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similaritie...Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.展开更多
The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,...The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.展开更多
BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the p...BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.展开更多
AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided in...AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.展开更多
Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in me...Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.展开更多
BACKGROUND Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes,metabolic syndrome,and cardiovascular diseases in adulthood.It is very important to identify relevant risk factors and...BACKGROUND Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes,metabolic syndrome,and cardiovascular diseases in adulthood.It is very important to identify relevant risk factors and intervene as early as possible.At present,the relationship between maternal and offspring metabolic factors is conflicting.AIM To estimate the association of maternal obesity and gestational diabetes mellitus(GDM)with overweight/obesity and fatty liver risk in offspring at 8 years of age.METHODS The prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of age.Offspring birth weight,sex,height,weight,and body mass index(BMI)were measured and calculated.FibroScan-502 examination with an M probe(Echosens,Paris,France)was prospectively conducted in offspring aged 8 years from the Shanghai Prenatal Cohort Study.RESULTS A total of 430 mother-child pairs were included in the analysis.A total of 62(14.2%)mothers were classified as obese,and 48(11.1%)were classified as having GDM.The mean age of the offspring at follow-up was 8 years old.Thirty-seven(8.6%)offspring were overweight,14(3.3%)had obesity,and 60(14.0%)had fatty liver.The prevalence of overweight,obesity and fatty liver in offspring increased significantly across maternal BMI quartiles(all P<0.05).Among offspring of mothers with GDM,12(25.0%)were overweight,4(8.3%)were obese,and 12(25.0%)had fatty liver vs.25(6.5%),10(2.6%)and 48(12.6%),respectively,for offspring of mothers without GDM(all P<0.05).In multiple logistic regression,after adjustment for variables,the OR for fatty liver in offspring was 8.26(95%CI:2.38-28.75)for maternal obesity and GDM.CONCLUSION This study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring,and GDM status also increases the odds of overweight/obesity in offspring.Weight management and glycemic control before and during pregnancy need to be highlighted in primary prevention of pediatric obesity and fatty liver.展开更多
AIM To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics in nonalcoholic fatty liver disease(NAFLD).METHODS Thirty-four biopsy-proven NAFLD patients from Northern, Cen...AIM To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics in nonalcoholic fatty liver disease(NAFLD).METHODS Thirty-four biopsy-proven NAFLD patients from Northern, Central, and Southern China were subjected to stratification by genotyping their single nucleotide polymorphisms(SNPs) in PNPLA3. Ultra performance liquid chromatography-tandem mass spectrometry was then employed to characterize the effects of PNPLA3 SNPs on serum lipidomics. In succession, correlation analysis revealed the association of PNPLA3-related lipid profile and hepatic pathological characteristics on a basis of steatosis, activity, and fibrosis assessment. The variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was finally performed so as to uncover the actions of lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alterations. RESULTS PNPLA3 SNPs(rs139051, rs738408, rs738409, rs 2072906, rs2294918, rs2294919, and rs4823173) demonstrated extensive association with the serum lipidomics, especially phospholipid metabolites [lysophosphatidylcholine(LPC), lysophosphatidylcholine plasmalogen(LPCO), lysophosphatdylethanolamine(LPE), phosphatidylcholine(PC), choline plasmalogen(PCO), phosphatidylethanolamine(PE), ethanolamine plasmalogen(PEO)], of NAFLD patients. PNPLA3 rs139051(A/A genotype) and rs2294918(G/G genotype) dominated the up-regulatory effect on phospholipids of LPCs(LPC 17:0, LPC 18:0, LPC 20:0, LPC 20:1, LPC 20:2) and LPCOs(LPC O-16:1, LPC O-18:1). Moreover, subjects with high-level LPCs/LPCOs were predisposed to low-grade lobular inflammation of NAFLD(rho:-0.407 to-0.585, P < 0.05-0.001). The significant correlation of PNPLA3 rs139051 and inflammation grading [A/A vs A/G + G/G: 0.50(0.00, 1.75) vs 1.50(1.00, 2.00), P < 0.05] further demonstrated its pathological role based on the modulation of phospholipid metabolite profile.CONCLUSION The A/A genotype at PNPLA3 rs139051 exerts an upregulatory effect on serum phospholipids of LPCs and LPCOs, which are associated with low-grade lobular inflammation of NAFLD.展开更多
Due to the energy-dense but nutrient-deficient diets,sedentary lifestyle and lack of exercise as well as an aging population,the prevalence and incidence of overweight/obesity/sarcopenic obesity,type 2 diabetes mellit...Due to the energy-dense but nutrient-deficient diets,sedentary lifestyle and lack of exercise as well as an aging population,the prevalence and incidence of overweight/obesity/sarcopenic obesity,type 2 diabetes mellitus(T2DM),metabolic syndrome and their related non-alcoholic fatty liver disease(NAFLD)have been increasing globally in the last two decades.In Europe and the United States,NAFLD has become the second leading cause of end-stage liver disease and liver transplantation(1).Worse still,the onset age of NAFLD is becoming younger tendency.Although the new nomenclature of metabolic dysfunction-associated fatty liver disease(MAFLD)has been proposed for 3 years,MAFLD is not equivalent to NAFLD,and few epidemiologic investigations on MAFLD to date.Therefore,this invited editorial is focus on the global epidemiology of NAFLD and the major impact on China.展开更多
With the rising epidemic of obesity,metabolic syndrome,and type 2 diabetes mellitus in China,metabolic dysfunctionassociated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease.This c...With the rising epidemic of obesity,metabolic syndrome,and type 2 diabetes mellitus in China,metabolic dysfunctionassociated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease.This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B.To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues,the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the“Guideline of prevention and treatment of non-alcoholic fatty liver disease(2018,China)”.The new edition,titled“Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease(Version 2024)”,offers comprehensive recommendations on key clinical issues,including screening and monitoring,diagnosis and evaluation,treatment,and followup for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease.Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease.Additionally,the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively.展开更多
Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases worldwid...Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases worldwide.Currently,lifestyle modification is the foremost guidelinerecommended management strategy for MASLD.However,it remains unclear which detrimental signals persist in MASLD even after disease remission.Thus,we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal.Methods:Male C57BL/6J mice were divided into three groups:Western diet(WD)feeding,chow diet(CD)feeding,or diet reversal from WD to CD.After 16 weeks of feeding,RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of MASLD.Additionally,RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized.Results:WD-induced MASLD triggered persistent activation of the DNA damage response(DDR)and its primary transcription factor,P53,long after the resolution of the hepatic phenotype through dietary reversal.Elevated levels of P53 might promote apoptosis,thereby exacerbating metabolic dysfunction-associated steatohepatitis,as they strongly correlated with hepatocyte ballooning,an indicator of apoptosis activation.Moreover,P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver.Mechanistically,P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease(AEN).Consistently,P53,AEN,and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal.Conclusions:The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD.Our findings provide new insights into the mechanisms of MASLD relapse,highlighting DDR signaling as a promising target to prevent MASLD recurrence.展开更多
Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is associated with metabolic disorders.This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.Methods:A ...Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is associated with metabolic disorders.This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.Methods:A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers.We compared the severity of fibrosis in patients with different components of metabolic disorders.Based on standard noninvasive tests and metabolic disorders,we developed new algorithms to identify advanced fibrosis.Results:Metabolic syndrome(MetS)was frequent in NAFLD patients(133/246,54%).Patients with MetS had a higher proportion of significant fibrosis(p=0.014)and higher LSM values(9.2 kPa,vs.7.4 kPa,p=0.002)than those without MetS.Patients with more metabolic disorders had higher fibrosis stages(p=0.017).Reduced highdensity lipoprotein cholesterol(odds ratio[OR]:2.241,95%confidence interval[CI]:1.004–5.002,p=0.049)and raised fasting glucose(OR:4.500,95%CI:2.083–9.725,p<0.001)were significantly associated with advanced fibrosis.Using these two metabolic disorders as a screening tool,a sensitivity,specificity and accuracy of 92%,81%and 83%was achieved,respectively.With the new algorithms combining metabolic disorders with noninvasive measurements,the number of patients requiring liver biopsy was reduced,especially in combination with the Fibrosis-4 score and metabolic disorders(36%to 17%,p<0.001).In addition,this stepwise algorithm could achieve a high accuracy(85%)and high negative predictive value(93%).Conclusions:Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis.With further validation and investigation,new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.展开更多
Background and Aims:Nonalcoholic fatty liver disease,now renamed metabolic dysfunction-associated fatty liver disease(MAFLD),is common in obese patients.Intragastric balloon(IGB),an obesity management tool with low co...Background and Aims:Nonalcoholic fatty liver disease,now renamed metabolic dysfunction-associated fatty liver disease(MAFLD),is common in obese patients.Intragastric balloon(IGB),an obesity management tool with low complication risk,might be used in MAFLD treatment but there is still unexplained heterogeneity in results across studies.Methods:We conducted a systematic search of 152 citations published up to September 2020.Meta-analyses,stratified analyses,and meta-regression were performed to evaluate the efficacy of IGB on homeostasis model assessment of insulin resistance(HOMA-IR),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transpeptidase(GGT),and to identify patients most appropriate for IGB therapy.Results:Thirteen observational studies and one randomized controlled trial met the inclusion criteria(624 participants in total).In the overall estimate,IGB therapy significantly improved the serum markers change from baseline to follow-up[HOMA-IR:1.56,95%confidence interval(CI)=1.16–1.95;ALT:11.53 U/L,95%CI=7.10–15.96;AST:6.79 U/L,95%CI=1.69–11.90;GGT:10.54 U/L,95%CI=6.32–14.75].In the stratified analysis,there were trends among participants with advanced age having less change in HOMA-IR(1.07 vs.1.82).The improvement of insulin resistance and liver biochemistries with swallowable IGB therapy was no worse than that with endoscopic IGB.Multivariate meta-regression analyses showed that greater HOMA-IR loss was predicted by younger age(p=0.0107).Furthermore,effectiveness on ALT and GGT was predicted by basal ALT(p=0.0004)and GGT(p=0.0026),respectively.Conclusions:IGB is effective among the serum markers of MAFLD.Younger patients had a greater decrease of HOMA-IR after IGB therapy.展开更多
Background and Aims:The concurrence of nonalcoholic steatohepatitis(NASH)and ulcerative colitis(UC)is increasingly seen in clinical practice,but the underlying mechanisms remain unclear.This study aimed to develop a m...Background and Aims:The concurrence of nonalcoholic steatohepatitis(NASH)and ulcerative colitis(UC)is increasingly seen in clinical practice,but the underlying mechanisms remain unclear.This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet(HFHCD)-induced NASH and dextran sulfate sodium(DSS)-induced UC,that would support mechanistic studies.Methods:Male C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling.The mice were divided into four subgroups for UC modeling:(1)A control group given a chow diet with normal drinking water;(2)A colitis group given chow diet with 2%DSS in drinking water;(3)A steatohepatitis group given HFHCD with normal drinking water;and(4)A steatohepatitis+colitis group given HFHCD with 2%DSS in drinking water.Results:NASH plus UC had high mortality(58.3%).Neither NASH nor UC alone were fatal.Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice,premorbid NASH significantly increased UC-related gut injury compared with UC alone.It was characterized by a significantly shorter colon,more colonic congestion,and a higher histopathological score(p<0.05).Inflammatory(tumor necrosis factor-alpha,interleukin 1 beta,C-C motif chemokine ligand 2,and nuclear factor kappa B)and apoptotic(Bcl2,Bad,Bim,and Bax)signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis+colitis compared with the other experimental groups.Conclusions:Premorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal phenotype.Potential links between NASH and UC pathogeneses can be investigated using this model.展开更多
基金National Key R&D Program of China,No.2017YFC0908900National Natural Science Foundation of China,No.81873565 and No.81900507Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.17CSK04 and No.15LC06.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic diseases in the world.Nowadays,the percentage of non-obese or lean patients with NAFLD is increasing.NAFLD in non-obese populations,especially the lean subgroup with a normal waist circumference(WC),might lead to more problems than obese individuals,as these individuals may not visit clinics for NAFLD diagnosis or ignore the diagnosis of NAFLD.If the precise characteristics of these populations,especially the lean subgroup,are identified,the clinicians would be able to provide more appropriate advice and treatment to these populations.AIM To investigate the prevalence,clinical characteristics,risk factors,and possible indicators for NAFLD in lean Chinese adults with a normal WC.METHODS People without diabetes mellitus or significant alcohol consumption who underwent routine health examinations were included.Their fatty liver index(FLI),abdominal ultrasonography results,and controlled attenuation parameter were all assessed.Genotyping for single-nucleotide polymorphisms associated with NAFLD was performed in another small group consisting of biopsy-proven NAFLD subjects and healthy controls.RESULTS A total of 2715 subjects who underwent routine health examinations were included in the study.Among 810 lean participants with a normal WC,142(17.5%)fulfilled the diagnostic criteria for NAFLD.Waist-height ratio,hemoglobin,platelets,and triglycerides were significant factors associated with the presence of NAFLD in these participants.The appropriate cut-off value of the FLI score in screening for NAFLD in the lean subjects with a normal WC was 25.15,which had a 77.8%sensitivity and 75.9%specificity.There was no significant difference in the single-nucleotide polymorphisms in the SIRT1,APOC3,PNPLA3,AGTR1,and PPARGC1A genes between lean subjects with and without NAFLD(P<0.05).CONCLUSION NAFLD is not uncommon in lean Chinese adults even with a normal WC.Metabolic factors,rather than genetic factors,may play important roles in the development of NAFLD in this population.A lower cut-off value of the FLI score in screening for NAFLD should be used for lean Chinese adults with a normal WC.
基金Supported by National Key Research and Development Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81873565 and No.81900507.
文摘With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly prevalent.The risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully characterized.In this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such patients.We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation.For CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses.The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.
基金supported by grants from the Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01)the National Natural Science Foundation of China (81873565 and 82100605)+2 种基金Shanghai Jiao Tong University Transmed Awards Research (20190104)Star Program of Shanghai Jiao Tong University (YG2021QN54)Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (17CSK04 and 15LC06)。
文摘Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.
基金Supported by the National Key Research and Development Program,No.2017YFC0908903National Natural Science Foundation of China,No.81873565 and No.81900507Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.17CSK04.
文摘The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.
基金Supported by National Key R and D Program of China,No.2017YFC0908903National Natural Science Foundation of China,No.81873565,No.81470840,and No.81800510Shanghai Sailing Program,No.18YF1415900
文摘BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.
基金Supported by National Key R&D Program of China No.2017YFC0908900National Key Basic Research Project,No.2012CB517501National Natural Science Foundation of China,No.81470840 and No.81600464
文摘AIM To evaluate the levels of mi R-192-5 p in non-alcoholic fatty liver disease(NAFLD) models and demonstrate the role of mi R-192-5 p in lipid accumulation. METHODS Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet(HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic mi R-192-5 p and stearoyl-Co A desaturase 1(SCD-1) levels were measured. Mi R-192-5 p mimic and inhibitor and SCD-1 si RNA were transfected into Huh7 cells exposed to palmitic acid(PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.RESULTS The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic mi R-192-5 p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection(P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of mi R-192-5 p and SCD-1 protein levels, respectively(P < 0.01). Transfection with mi R-192-5 p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively(P < 0.01). Luciferase activity was suppressed and enhanced by mi R-192-5 p mimic and inhibitor, respectively, in wild-type SCD-1(P < 0.01) but not in mutant SCD-1. Mi R-192-5 p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 si RNA transfection abrogated the lipid deposition aggravated by mi R-192-5 p inhibitor(P < 0.01).CONCLUSION This study demonstrates that mi R-192-5 p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.
基金This study was supported by a grant from Sanofi(China)Investment Co.,Ltd.
文摘Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional study.Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China.Anthropometric and metabolic parameters were collected to assess the pathological relevance.Results:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met S.With the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably increased.The comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of NASH.However,the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis.Among the 246 patients,239(97.2%)met the diagnostic criteria of MAFLD.Although non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and cirrhosis.In the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and diabetes.Conclusions:Metabolic dysregulations are important risk factors in NAFLD progression.The insulin resistance status may play a predominant role in the progression in MAFLD patients.
基金Supported by Collaborative Innovation Program of Shanghai Municipal Health Commission, No. 2020CXJQ01National Natural Science Foundation of China, No. 81873565 and No. 82100605+3 种基金SJTU Trans-med Awards Research, No. 20190104Star Program of Shanghai Jiao Tong University, No. YG2021QN54WBE Liver Fibrosis Foundation, No. CFHPC2020061Hospital Funded Clinical Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 17CSK04 and No. 15LC06
文摘BACKGROUND Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes,metabolic syndrome,and cardiovascular diseases in adulthood.It is very important to identify relevant risk factors and intervene as early as possible.At present,the relationship between maternal and offspring metabolic factors is conflicting.AIM To estimate the association of maternal obesity and gestational diabetes mellitus(GDM)with overweight/obesity and fatty liver risk in offspring at 8 years of age.METHODS The prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of age.Offspring birth weight,sex,height,weight,and body mass index(BMI)were measured and calculated.FibroScan-502 examination with an M probe(Echosens,Paris,France)was prospectively conducted in offspring aged 8 years from the Shanghai Prenatal Cohort Study.RESULTS A total of 430 mother-child pairs were included in the analysis.A total of 62(14.2%)mothers were classified as obese,and 48(11.1%)were classified as having GDM.The mean age of the offspring at follow-up was 8 years old.Thirty-seven(8.6%)offspring were overweight,14(3.3%)had obesity,and 60(14.0%)had fatty liver.The prevalence of overweight,obesity and fatty liver in offspring increased significantly across maternal BMI quartiles(all P<0.05).Among offspring of mothers with GDM,12(25.0%)were overweight,4(8.3%)were obese,and 12(25.0%)had fatty liver vs.25(6.5%),10(2.6%)and 48(12.6%),respectively,for offspring of mothers without GDM(all P<0.05).In multiple logistic regression,after adjustment for variables,the OR for fatty liver in offspring was 8.26(95%CI:2.38-28.75)for maternal obesity and GDM.CONCLUSION This study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring,and GDM status also increases the odds of overweight/obesity in offspring.Weight management and glycemic control before and during pregnancy need to be highlighted in primary prevention of pediatric obesity and fatty liver.
基金Supported by National Key Research and Development Plan "Precision Medicine Research",No.2017YFC0908903National Natural Science Foundation of China,No.81070346,No.81270492,No.81470859,No.81270491 and No.81470840+2 种基金State Key Development Program for Basic Research of China,No.2012CB517501100 Talents Program,No.XBR2011007hProgram of the Committee of Science and Technology,No.09140903500
文摘AIM To investigate the effect of PNPLA3 polymorphisms on serum lipidomics and pathological characteristics in nonalcoholic fatty liver disease(NAFLD).METHODS Thirty-four biopsy-proven NAFLD patients from Northern, Central, and Southern China were subjected to stratification by genotyping their single nucleotide polymorphisms(SNPs) in PNPLA3. Ultra performance liquid chromatography-tandem mass spectrometry was then employed to characterize the effects of PNPLA3 SNPs on serum lipidomics. In succession, correlation analysis revealed the association of PNPLA3-related lipid profile and hepatic pathological characteristics on a basis of steatosis, activity, and fibrosis assessment. The variant-based scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was finally performed so as to uncover the actions of lipidomics-affecting PNPLA3 SNPs in NAFLD-specific pathological alterations. RESULTS PNPLA3 SNPs(rs139051, rs738408, rs738409, rs 2072906, rs2294918, rs2294919, and rs4823173) demonstrated extensive association with the serum lipidomics, especially phospholipid metabolites [lysophosphatidylcholine(LPC), lysophosphatidylcholine plasmalogen(LPCO), lysophosphatdylethanolamine(LPE), phosphatidylcholine(PC), choline plasmalogen(PCO), phosphatidylethanolamine(PE), ethanolamine plasmalogen(PEO)], of NAFLD patients. PNPLA3 rs139051(A/A genotype) and rs2294918(G/G genotype) dominated the up-regulatory effect on phospholipids of LPCs(LPC 17:0, LPC 18:0, LPC 20:0, LPC 20:1, LPC 20:2) and LPCOs(LPC O-16:1, LPC O-18:1). Moreover, subjects with high-level LPCs/LPCOs were predisposed to low-grade lobular inflammation of NAFLD(rho:-0.407 to-0.585, P < 0.05-0.001). The significant correlation of PNPLA3 rs139051 and inflammation grading [A/A vs A/G + G/G: 0.50(0.00, 1.75) vs 1.50(1.00, 2.00), P < 0.05] further demonstrated its pathological role based on the modulation of phospholipid metabolite profile.CONCLUSION The A/A genotype at PNPLA3 rs139051 exerts an upregulatory effect on serum phospholipids of LPCs and LPCOs, which are associated with low-grade lobular inflammation of NAFLD.
基金supported by the National Natural Science Foundation of China(Nos.82170593,81900507).
文摘Due to the energy-dense but nutrient-deficient diets,sedentary lifestyle and lack of exercise as well as an aging population,the prevalence and incidence of overweight/obesity/sarcopenic obesity,type 2 diabetes mellitus(T2DM),metabolic syndrome and their related non-alcoholic fatty liver disease(NAFLD)have been increasing globally in the last two decades.In Europe and the United States,NAFLD has become the second leading cause of end-stage liver disease and liver transplantation(1).Worse still,the onset age of NAFLD is becoming younger tendency.Although the new nomenclature of metabolic dysfunction-associated fatty liver disease(MAFLD)has been proposed for 3 years,MAFLD is not equivalent to NAFLD,and few epidemiologic investigations on MAFLD to date.Therefore,this invited editorial is focus on the global epidemiology of NAFLD and the major impact on China.
基金supported by the National Science and Technology Major Project of China(No:2023ZD0508700).
文摘With the rising epidemic of obesity,metabolic syndrome,and type 2 diabetes mellitus in China,metabolic dysfunctionassociated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease.This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B.To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues,the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the“Guideline of prevention and treatment of non-alcoholic fatty liver disease(2018,China)”.The new edition,titled“Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease(Version 2024)”,offers comprehensive recommendations on key clinical issues,including screening and monitoring,diagnosis and evaluation,treatment,and followup for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease.Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease.Additionally,the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39020600)the National Natural Science Foundation of China(81900507,82100606,82170593,82222071,91957116)the Shanghai Municipal Science and Technology Major Project.
文摘Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases worldwide.Currently,lifestyle modification is the foremost guidelinerecommended management strategy for MASLD.However,it remains unclear which detrimental signals persist in MASLD even after disease remission.Thus,we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal.Methods:Male C57BL/6J mice were divided into three groups:Western diet(WD)feeding,chow diet(CD)feeding,or diet reversal from WD to CD.After 16 weeks of feeding,RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of MASLD.Additionally,RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized.Results:WD-induced MASLD triggered persistent activation of the DNA damage response(DDR)and its primary transcription factor,P53,long after the resolution of the hepatic phenotype through dietary reversal.Elevated levels of P53 might promote apoptosis,thereby exacerbating metabolic dysfunction-associated steatohepatitis,as they strongly correlated with hepatocyte ballooning,an indicator of apoptosis activation.Moreover,P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver.Mechanistically,P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease(AEN).Consistently,P53,AEN,and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal.Conclusions:The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD.Our findings provide new insights into the mechanisms of MASLD relapse,highlighting DDR signaling as a promising target to prevent MASLD recurrence.
基金This study was funded by Sanofi(China)Investment Co.,Ltdthe National Key R&D Program of China(No.2017YFC090890).
文摘Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is associated with metabolic disorders.This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients.Methods:A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers.We compared the severity of fibrosis in patients with different components of metabolic disorders.Based on standard noninvasive tests and metabolic disorders,we developed new algorithms to identify advanced fibrosis.Results:Metabolic syndrome(MetS)was frequent in NAFLD patients(133/246,54%).Patients with MetS had a higher proportion of significant fibrosis(p=0.014)and higher LSM values(9.2 kPa,vs.7.4 kPa,p=0.002)than those without MetS.Patients with more metabolic disorders had higher fibrosis stages(p=0.017).Reduced highdensity lipoprotein cholesterol(odds ratio[OR]:2.241,95%confidence interval[CI]:1.004–5.002,p=0.049)and raised fasting glucose(OR:4.500,95%CI:2.083–9.725,p<0.001)were significantly associated with advanced fibrosis.Using these two metabolic disorders as a screening tool,a sensitivity,specificity and accuracy of 92%,81%and 83%was achieved,respectively.With the new algorithms combining metabolic disorders with noninvasive measurements,the number of patients requiring liver biopsy was reduced,especially in combination with the Fibrosis-4 score and metabolic disorders(36%to 17%,p<0.001).In addition,this stepwise algorithm could achieve a high accuracy(85%)and high negative predictive value(93%).Conclusions:Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis.With further validation and investigation,new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.
基金This study was supported by the National Key R&D Program of China(2017YFC0908903)National Natural Science Foundation of China(81873565,81900507)Shanghai Leading Talent Plan 2017,Innovative Research Team of High-Level Local Universities in Shanghai,and Hospital Funded Clinical Research,Clinical Research Unit,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(17CSK04).
文摘Background and Aims:Nonalcoholic fatty liver disease,now renamed metabolic dysfunction-associated fatty liver disease(MAFLD),is common in obese patients.Intragastric balloon(IGB),an obesity management tool with low complication risk,might be used in MAFLD treatment but there is still unexplained heterogeneity in results across studies.Methods:We conducted a systematic search of 152 citations published up to September 2020.Meta-analyses,stratified analyses,and meta-regression were performed to evaluate the efficacy of IGB on homeostasis model assessment of insulin resistance(HOMA-IR),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transpeptidase(GGT),and to identify patients most appropriate for IGB therapy.Results:Thirteen observational studies and one randomized controlled trial met the inclusion criteria(624 participants in total).In the overall estimate,IGB therapy significantly improved the serum markers change from baseline to follow-up[HOMA-IR:1.56,95%confidence interval(CI)=1.16–1.95;ALT:11.53 U/L,95%CI=7.10–15.96;AST:6.79 U/L,95%CI=1.69–11.90;GGT:10.54 U/L,95%CI=6.32–14.75].In the stratified analysis,there were trends among participants with advanced age having less change in HOMA-IR(1.07 vs.1.82).The improvement of insulin resistance and liver biochemistries with swallowable IGB therapy was no worse than that with endoscopic IGB.Multivariate meta-regression analyses showed that greater HOMA-IR loss was predicted by younger age(p=0.0107).Furthermore,effectiveness on ALT and GGT was predicted by basal ALT(p=0.0004)and GGT(p=0.0026),respectively.Conclusions:IGB is effective among the serum markers of MAFLD.Younger patients had a greater decrease of HOMA-IR after IGB therapy.
基金supported by the National Key Research and Development Program,No.2017YFC0908903National Natural Science Foundation of China,No.81873565,81900507,82170593.
文摘Background and Aims:The concurrence of nonalcoholic steatohepatitis(NASH)and ulcerative colitis(UC)is increasingly seen in clinical practice,but the underlying mechanisms remain unclear.This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet(HFHCD)-induced NASH and dextran sulfate sodium(DSS)-induced UC,that would support mechanistic studies.Methods:Male C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling.The mice were divided into four subgroups for UC modeling:(1)A control group given a chow diet with normal drinking water;(2)A colitis group given chow diet with 2%DSS in drinking water;(3)A steatohepatitis group given HFHCD with normal drinking water;and(4)A steatohepatitis+colitis group given HFHCD with 2%DSS in drinking water.Results:NASH plus UC had high mortality(58.3%).Neither NASH nor UC alone were fatal.Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice,premorbid NASH significantly increased UC-related gut injury compared with UC alone.It was characterized by a significantly shorter colon,more colonic congestion,and a higher histopathological score(p<0.05).Inflammatory(tumor necrosis factor-alpha,interleukin 1 beta,C-C motif chemokine ligand 2,and nuclear factor kappa B)and apoptotic(Bcl2,Bad,Bim,and Bax)signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis+colitis compared with the other experimental groups.Conclusions:Premorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal phenotype.Potential links between NASH and UC pathogeneses can be investigated using this model.
