BACKGROUND High venous ammonia(VA)values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis(LC)as well as acute hepatitis.Moreover,VA has been associated with poo...BACKGROUND High venous ammonia(VA)values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis(LC)as well as acute hepatitis.Moreover,VA has been associated with poor prognosis and high mortality in these clinical settings.However,the role of ammonia in acuteon-chronic liver failure(ACLF)has not yet been clearly established.AIM To assess the role of VA in predicting the outcome of cirrhotic patients with ACLF in a tertiary care center.METHODS We performed a retrospective observational study including consecutive patients with LC hospitalized for acute non-elective indications such as ascites,hepatic encephalopathy(HE),upper gastrointestinal bleeding,or bacterial infections that fulfilled the Asian Pacific Association for the Study of the Liver(APASL)criteria for ACLF.The study was conducted in“St.Spiridon”University Hospital,Iasi,Romania,a tertiary care center,between January 2017 and January 2019.The APASL ACLF Research Consortium(AARC)score was calculated and ACLF grade was established accordingly.West-haven classification was used for HE.Statistical analysis was performed using IBM SPSS version 22.0.RESULTS Four hundred and forty-six patients were included,aged 59(50-65)years,57.4%men.Child-Pugh,model for end-stage liver disease(MELD)and AARC scores were 11(10-12),19.13±6.79,and 7(6-8),respectively.66.4%had ACLF grade I,31.2%ACLF grade II,and 2.5%ACLF grade III.HE was diagnosed in 83.9%,34%grade I,37.2%grade II,23.5%grade III,and 5.3%grade IV.Overall mortality was 7.8%.VA was 103(78-148)μmol/L.Receiver operating characteristic analysis showed good accuracy for the prediction of in-hospital mortality for the AARC score[Area under the curve(AUC)=0.886],MELD score(AUC=0.816),VA(AUC=0.812)and a fair accuracy for the Child-Pugh score(AUC=0.799).Subsequently,a cut-off value for the prediction of mortality was identified for VA(152.5μmol/L,sensitivity=0.706,1-specificity=0.190).Univariate analysis found acute kidney injury,severe HE(grade III or IV),VA≥152.5μmol/L,MELD score≥22.5,Child-Pugh score≥12.5,and AARC score≥8.5 to be associated with inhospital mortality.Multivariate analysis identified AARC score≥8.5 and venous ammonia≥152μmol/L to be independent predictors of in-hospital mortality.CONCLUSION VA could be used as an inexpensive predictor of in-hospital mortality in patients with ACLF.Patients with both ACLF and VA>152.5μmol/L have a high risk for a poor outcome.展开更多
Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1...Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.展开更多
BACKGROUND Previous research has highlighted correlations between blood cell counts and chronic liver disease.Nonetheless,the causal relationships remain unknown.AIM To evaluate the causal effect of blood cell traits ...BACKGROUND Previous research has highlighted correlations between blood cell counts and chronic liver disease.Nonetheless,the causal relationships remain unknown.AIM To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease(NAFLD)risk.METHODS Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study(GWAS)conducted by the Blood Cell Consortium.Summary-level data for liver enzymes were obtained from the United Kingdom Biobank.NAFLD data were obtained from a GWAS meta-analysis(8434 cases and 770180 controls,discovery dataset)and the Fingen GWAS(2275 cases and 372727 controls,replication dataset).This analysis was conducted using the inverse-variance weighted method,followed by various sensitivity analyses.RESULTS One SD increase in the genetically predicted haemoglobin concentration(HGB)was associated with aβof 0.0078(95%CI:0.0059-0.0096),0.0108(95%CI:0.0080-0.0136),0.0361(95%CI:0.0156-0.0567),and 0.0083(95%CI:00046-0.0121)for alkaline phosphatase(ALP),alanine aminotransferase(ALT),aspartate aminotransferase,and gammaglutamyl transferase,respectively.Genetically predicted haematocrit was associated with ALP(β=0.0078,95%CI:0.0052-0.0104)and ALT(β=0.0057,95%CI:0.0039-0.0075).Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD[odds ratio(OR)=1.199,95%CI:1.087-1.322]and(OR=1.157,95%CI:1.071-1.250).The results of the sensitivity analyses remained significant.CONCLUSION Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis,which may facilitate the diagnosis and prevention of NAFLD.展开更多
AIM： To compare the diagnostic capability of multidetector computed tomography （MDCT） and magnetic resonance imaging （MRI） for the detection of hepatocellular carcinoma （HCC） tumour nodules and their effect on ...AIM： To compare the diagnostic capability of multidetector computed tomography （MDCT） and magnetic resonance imaging （MRI） for the detection of hepatocellular carcinoma （HCC） tumour nodules and their effect on patient management. METHODS： A total of 28 patients （25 male, 3 female, mean age 67 ± 10.8 years） with biopsy-proven HCC were investigated with 64-row MDCT （slice 3 mm native, arterial and portal-venous phase, 120 mL Iomeprol, 4 mL/s, delay by bolus trigger） and MRI （Tlfs fl2d TE/ TR 2.72/129 ms, T2tse TE/TR 102/4000 ms, 5-phase dynamic contrast-enhanced Tlfs fl3d TE/TR 1.56/4.6, Gadolinium-DTPA, slice 4 mm）. Consensus reading of both modalities was used as reference. Tumour nodules were analyzed with respect to number, size, and location. RESULTS： In total, 162 tumour nodules were detected by consensus reading. MRI detected significantly more tumour nodules （159 vs 123, P 〈 0.001） compared to MDCT, with the best sensitivity for early arterial phase MRI. False-negative CT findings included nodules ≤ 5 mm （n = 5）, ≤ 10 mm （n = 17）, ≤ 15 mm （n= 12）,≤20mm（n=4）,andlnodule〉20mm.MRI missed 2 nodules ≤ 10 mm and 1 nodule ≤ 15 mm. On MRI, nodule diameters were greater than on CT （29.2 ≤25.1 mm, range 5-140 mm vs 24.1 ± 22.7 mm, range 4-129 mm, P 〈 0.005）. In 2 patients, MDCT showed only unilobar tumour spread, whereas MRI revealed additional nodules in the contralateral lobe. Detection of these nodules could have changed the therapeutic strategy. CONCLUSION： Contrast-enhanced MRI is superior to 64-row MDCT for the detection of HCC nodules. Patients should be allocated to interventional or operative treatment according to a dedicated MRI-protocol.展开更多
AIM: To investigate genetic susceptibility in Indian subjects with non-alcoholic fatty liver disease(NAFLD) by performing a pooled genetic study.METHODS: Study subjects(n = 306) were recruited and categorized into NAF...AIM: To investigate genetic susceptibility in Indian subjects with non-alcoholic fatty liver disease(NAFLD) by performing a pooled genetic study.METHODS: Study subjects(n = 306) were recruited and categorized into NAFLD and control groups based on ultrasound findings of fatty infiltration. Of the 306 individuals, 156 individuals had fatty infiltration and thus comprised the NAFLD group. One hundred and fifty(n = 150) individuals were normal, without fatty infiltration of the liver, comprising the control group. Blood samples, demographic and anthropometric data from the individuals were collected after obtaining informed consent. Anthropometric data, blood glucose, lipids and liver function tests were estimated using standard methods. Genome wide association stud-ies done to date on NAFLD were identified, 19 single nucleotide polymorphisms(SNPs) were selected from these studies that were reported to be significantly associated with NAFLD and genotyping was performed on the Sequenom platform. Student's t test for continuous variables and χ2 test was applied to variant carriers from both groups. Required corrections were applied as multiple testing was done.RESULTS The mean age of the control group was 39.78 ± 10.83 and the NAFLD group was 36.63 ± 8.20 years. The waist circumference of males and females in the control and NAFLD groups were 80.13 ± 10.35; 81.77 ± 13.65 and 94.09 ± 10.53; 92.53 ± 8.27 respectively. The mean triglyceride and alanine transaminase(ALT) levels in the control and NAFLD groups were 135.18 ± 7.77; 25.39 ± 14.73 and 184.40 ± 84.31; 110.20 ± 67.05 respectively. When χ2 test was applied to the number of individuals carrying the variant risk alleles between the control and NAFLD group, a significant association was seen between rs738409 of the patatin-like phospholipase domain containing 3(PNPLA3) gene(P = 0.001), rs2073080 of the PARVB gene(P = 0.02), rs2143571 of SAMM50 gene(P = 0.05) and rs6487679 of the pregnancy zone protein(PZP) gene(P = 0.01) with the disease. Variant single nucleotide polymorphisms(SNPs) in NCAN and PNPLA3 gene were associated with higher levels of ALT, whereas variant SNPs in APOC3, PNPLA3, EFCAB4 B and COL13A1 were associated with high triglyceride levels. Apart from the above associations, rs2073080, rs343062 and rs6591182 were significantly associated with high BMI; rs2854117 and rs738409 with high triglyceride levels; and rs2073080, rs2143571, rs2228603, rs6487679 and rs738409 with high ALT levels.CONCLUSION: Pooled genetic analysis revealed an association of SNPs in PNPLA3, PARVB, SAMM50 and PZP genes with NAFLD. SNPs in NCAN and PNPLA3gene were associated with higher levels of ALT,whereas variant SNPs in APOC3, PNPLA3, EFCAB4 B and COL13A1 were associated with high triglyceride levels.展开更多
The 2023 practice guidance on primary sclerosing cholangitis(PSC)and cholangiocarcinoma(CCA)of the American Association for the Study of Liver Diseases(AASLD)came as a needful update to the previous 2010 guidelines on...The 2023 practice guidance on primary sclerosing cholangitis(PSC)and cholangiocarcinoma(CCA)of the American Association for the Study of Liver Diseases(AASLD)came as a needful update to the previous 2010 guidelines on PSC,with a first-time inclusion of dedicated guidance on the diagnosis and management of CCA(1,2).This data-supported approach developed by consensus of an expert panel,provides guidance statements based on analytical review of the relevant literature.展开更多
With the increasing clinical use of cytostatic and novel biologic targeted agents,conventional morphologic tumor burden assessments,including World Health Organization criteria and Response Evaluation Criteria in Soli...With the increasing clinical use of cytostatic and novel biologic targeted agents,conventional morphologic tumor burden assessments,including World Health Organization criteria and Response Evaluation Criteria in Solid Tumors,are confronting limitations because of their difficulties in distinguishing viable tumor from necrotic or fibrotic tissue.Therefore,the investigation for reliable quantitative biomarkers of therapeutic response such as metabolic imaging or functional imaging has been desired.In this review,we will discuss the conventional and new approaches to assess tumor burden.Since targeted therapy or locoregional therapies can induce biological changes much earlier than morphological changes,these functional tumor burden analyses are very promising.However,some of them have not gone thorough all steps for standardization and validation.Nevertheless,these new techniques and criteria will play an important role in the cancer management,and provide each patient more tailored therapy.展开更多
Non-alcoholic fatty liver disease （NAFLD） is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet （LD）, the main organelle involved in neutral lipid storage and hyd...Non-alcoholic fatty liver disease （NAFLD） is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet （LD）, the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treat- ment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies （GWAS）, genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 （17β- HSD13） may promote the development of NAFLD.展开更多
Background:Bile leaks are one of the most common complications after liver resection.The International Study Group of Liver Surgery(ISGLS)established a uniform bile leak definition including a severity grading.However...Background:Bile leaks are one of the most common complications after liver resection.The International Study Group of Liver Surgery(ISGLS)established a uniform bile leak definition including a severity grading.However,a risk factor assessment according to ISGLS grading as well as the clinical implications has not been studied sufficiently so far.Methods:The incidence and grading of bile leaks according to ISGLS were prospectively documented in 501 consecutive liver resections between July 2012 and December 2016.A multivariate regression analysis was performed for risk factor assessment.Association with other surgical complications,90-day mortality as well as length of hospital stay(LOS)was studied.Results:The total rate of bile leaks in this cohort was 14.0%:2.8%grade A,8.0%grade B,and 3.2%grade C bile leaks were observed.Preoperative chemotherapy or biliary intervention,diagnosis of hilar cholangiocarcinoma,colorectal metastasis,central minor liver resection,major hepatectomy,extended hepatectomy or two-stage hepatectomy,were some of the risk factors leading to bile leaks.The multivariate regression analysis revealed that preoperative chemotherapy,major hepatectomy and biliodigestive reconstruction remained significant independent risk factors for bile leaks.Grade C bile leaks were associated not only with surgical site infection,but also with an increased 90-day mortality and prolonged LOS.Conclusions:The preoperative treatment as well as the surgical procedure had significant influence on the incidence and the severity of bile leaks.Grade C bile leaks were clinically most relevant,and led to significant increased LOS,rate of infection,and mortality.展开更多
Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disea...Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.展开更多
文摘BACKGROUND High venous ammonia(VA)values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis(LC)as well as acute hepatitis.Moreover,VA has been associated with poor prognosis and high mortality in these clinical settings.However,the role of ammonia in acuteon-chronic liver failure(ACLF)has not yet been clearly established.AIM To assess the role of VA in predicting the outcome of cirrhotic patients with ACLF in a tertiary care center.METHODS We performed a retrospective observational study including consecutive patients with LC hospitalized for acute non-elective indications such as ascites,hepatic encephalopathy(HE),upper gastrointestinal bleeding,or bacterial infections that fulfilled the Asian Pacific Association for the Study of the Liver(APASL)criteria for ACLF.The study was conducted in“St.Spiridon”University Hospital,Iasi,Romania,a tertiary care center,between January 2017 and January 2019.The APASL ACLF Research Consortium(AARC)score was calculated and ACLF grade was established accordingly.West-haven classification was used for HE.Statistical analysis was performed using IBM SPSS version 22.0.RESULTS Four hundred and forty-six patients were included,aged 59(50-65)years,57.4%men.Child-Pugh,model for end-stage liver disease(MELD)and AARC scores were 11(10-12),19.13±6.79,and 7(6-8),respectively.66.4%had ACLF grade I,31.2%ACLF grade II,and 2.5%ACLF grade III.HE was diagnosed in 83.9%,34%grade I,37.2%grade II,23.5%grade III,and 5.3%grade IV.Overall mortality was 7.8%.VA was 103(78-148)μmol/L.Receiver operating characteristic analysis showed good accuracy for the prediction of in-hospital mortality for the AARC score[Area under the curve(AUC)=0.886],MELD score(AUC=0.816),VA(AUC=0.812)and a fair accuracy for the Child-Pugh score(AUC=0.799).Subsequently,a cut-off value for the prediction of mortality was identified for VA(152.5μmol/L,sensitivity=0.706,1-specificity=0.190).Univariate analysis found acute kidney injury,severe HE(grade III or IV),VA≥152.5μmol/L,MELD score≥22.5,Child-Pugh score≥12.5,and AARC score≥8.5 to be associated with inhospital mortality.Multivariate analysis identified AARC score≥8.5 and venous ammonia≥152μmol/L to be independent predictors of in-hospital mortality.CONCLUSION VA could be used as an inexpensive predictor of in-hospital mortality in patients with ACLF.Patients with both ACLF and VA>152.5μmol/L have a high risk for a poor outcome.
基金supported by grants from the National Natural Science Foundation of China[No.81872641]Natural Science Foundation of Hunan Province[No.2023JJ40357].
文摘Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.
基金the Shanghai Natural Science Foundation of China,No.23ZR1447800and the Fengxian District Science and Technology Commission Project,China,No.20211838.
文摘BACKGROUND Previous research has highlighted correlations between blood cell counts and chronic liver disease.Nonetheless,the causal relationships remain unknown.AIM To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease(NAFLD)risk.METHODS Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study(GWAS)conducted by the Blood Cell Consortium.Summary-level data for liver enzymes were obtained from the United Kingdom Biobank.NAFLD data were obtained from a GWAS meta-analysis(8434 cases and 770180 controls,discovery dataset)and the Fingen GWAS(2275 cases and 372727 controls,replication dataset).This analysis was conducted using the inverse-variance weighted method,followed by various sensitivity analyses.RESULTS One SD increase in the genetically predicted haemoglobin concentration(HGB)was associated with aβof 0.0078(95%CI:0.0059-0.0096),0.0108(95%CI:0.0080-0.0136),0.0361(95%CI:0.0156-0.0567),and 0.0083(95%CI:00046-0.0121)for alkaline phosphatase(ALP),alanine aminotransferase(ALT),aspartate aminotransferase,and gammaglutamyl transferase,respectively.Genetically predicted haematocrit was associated with ALP(β=0.0078,95%CI:0.0052-0.0104)and ALT(β=0.0057,95%CI:0.0039-0.0075).Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD[odds ratio(OR)=1.199,95%CI:1.087-1.322]and(OR=1.157,95%CI:1.071-1.250).The results of the sensitivity analyses remained significant.CONCLUSION Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis,which may facilitate the diagnosis and prevention of NAFLD.
文摘AIM： To compare the diagnostic capability of multidetector computed tomography （MDCT） and magnetic resonance imaging （MRI） for the detection of hepatocellular carcinoma （HCC） tumour nodules and their effect on patient management. METHODS： A total of 28 patients （25 male, 3 female, mean age 67 ± 10.8 years） with biopsy-proven HCC were investigated with 64-row MDCT （slice 3 mm native, arterial and portal-venous phase, 120 mL Iomeprol, 4 mL/s, delay by bolus trigger） and MRI （Tlfs fl2d TE/ TR 2.72/129 ms, T2tse TE/TR 102/4000 ms, 5-phase dynamic contrast-enhanced Tlfs fl3d TE/TR 1.56/4.6, Gadolinium-DTPA, slice 4 mm）. Consensus reading of both modalities was used as reference. Tumour nodules were analyzed with respect to number, size, and location. RESULTS： In total, 162 tumour nodules were detected by consensus reading. MRI detected significantly more tumour nodules （159 vs 123, P 〈 0.001） compared to MDCT, with the best sensitivity for early arterial phase MRI. False-negative CT findings included nodules ≤ 5 mm （n = 5）, ≤ 10 mm （n = 17）, ≤ 15 mm （n= 12）,≤20mm（n=4）,andlnodule〉20mm.MRI missed 2 nodules ≤ 10 mm and 1 nodule ≤ 15 mm. On MRI, nodule diameters were greater than on CT （29.2 ≤25.1 mm, range 5-140 mm vs 24.1 ± 22.7 mm, range 4-129 mm, P 〈 0.005）. In 2 patients, MDCT showed only unilobar tumour spread, whereas MRI revealed additional nodules in the contralateral lobe. Detection of these nodules could have changed the therapeutic strategy. CONCLUSION： Contrast-enhanced MRI is superior to 64-row MDCT for the detection of HCC nodules. Patients should be allocated to interventional or operative treatment according to a dedicated MRI-protocol.
文摘AIM: To investigate genetic susceptibility in Indian subjects with non-alcoholic fatty liver disease(NAFLD) by performing a pooled genetic study.METHODS: Study subjects(n = 306) were recruited and categorized into NAFLD and control groups based on ultrasound findings of fatty infiltration. Of the 306 individuals, 156 individuals had fatty infiltration and thus comprised the NAFLD group. One hundred and fifty(n = 150) individuals were normal, without fatty infiltration of the liver, comprising the control group. Blood samples, demographic and anthropometric data from the individuals were collected after obtaining informed consent. Anthropometric data, blood glucose, lipids and liver function tests were estimated using standard methods. Genome wide association stud-ies done to date on NAFLD were identified, 19 single nucleotide polymorphisms(SNPs) were selected from these studies that were reported to be significantly associated with NAFLD and genotyping was performed on the Sequenom platform. Student's t test for continuous variables and χ2 test was applied to variant carriers from both groups. Required corrections were applied as multiple testing was done.RESULTS The mean age of the control group was 39.78 ± 10.83 and the NAFLD group was 36.63 ± 8.20 years. The waist circumference of males and females in the control and NAFLD groups were 80.13 ± 10.35; 81.77 ± 13.65 and 94.09 ± 10.53; 92.53 ± 8.27 respectively. The mean triglyceride and alanine transaminase(ALT) levels in the control and NAFLD groups were 135.18 ± 7.77; 25.39 ± 14.73 and 184.40 ± 84.31; 110.20 ± 67.05 respectively. When χ2 test was applied to the number of individuals carrying the variant risk alleles between the control and NAFLD group, a significant association was seen between rs738409 of the patatin-like phospholipase domain containing 3(PNPLA3) gene(P = 0.001), rs2073080 of the PARVB gene(P = 0.02), rs2143571 of SAMM50 gene(P = 0.05) and rs6487679 of the pregnancy zone protein(PZP) gene(P = 0.01) with the disease. Variant single nucleotide polymorphisms(SNPs) in NCAN and PNPLA3 gene were associated with higher levels of ALT, whereas variant SNPs in APOC3, PNPLA3, EFCAB4 B and COL13A1 were associated with high triglyceride levels. Apart from the above associations, rs2073080, rs343062 and rs6591182 were significantly associated with high BMI; rs2854117 and rs738409 with high triglyceride levels; and rs2073080, rs2143571, rs2228603, rs6487679 and rs738409 with high ALT levels.CONCLUSION: Pooled genetic analysis revealed an association of SNPs in PNPLA3, PARVB, SAMM50 and PZP genes with NAFLD. SNPs in NCAN and PNPLA3gene were associated with higher levels of ALT,whereas variant SNPs in APOC3, PNPLA3, EFCAB4 B and COL13A1 were associated with high triglyceride levels.
文摘The 2023 practice guidance on primary sclerosing cholangitis(PSC)and cholangiocarcinoma(CCA)of the American Association for the Study of Liver Diseases(AASLD)came as a needful update to the previous 2010 guidelines on PSC,with a first-time inclusion of dedicated guidance on the diagnosis and management of CCA(1,2).This data-supported approach developed by consensus of an expert panel,provides guidance statements based on analytical review of the relevant literature.
文摘With the increasing clinical use of cytostatic and novel biologic targeted agents,conventional morphologic tumor burden assessments,including World Health Organization criteria and Response Evaluation Criteria in Solid Tumors,are confronting limitations because of their difficulties in distinguishing viable tumor from necrotic or fibrotic tissue.Therefore,the investigation for reliable quantitative biomarkers of therapeutic response such as metabolic imaging or functional imaging has been desired.In this review,we will discuss the conventional and new approaches to assess tumor burden.Since targeted therapy or locoregional therapies can induce biological changes much earlier than morphological changes,these functional tumor burden analyses are very promising.However,some of them have not gone thorough all steps for standardization and validation.Nevertheless,these new techniques and criteria will play an important role in the cancer management,and provide each patient more tailored therapy.
基金The authors thank Dr. John Zehmer for his critical reading and useful suggestions. This work was supported by the National Natural Science Foundation of China （Grant No. 31100854 and U 1402225）, the Ministry of Science and Technology of China （Grant No. 2016YFA0500100）, the Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions （CIT＆TCD201504086）.
文摘Non-alcoholic fatty liver disease （NAFLD） is an epidemic metabolic condition driven by an underlying lipid homeostasis disorder. The lipid droplet （LD）, the main organelle involved in neutral lipid storage and hydrolysis, is a potential target for NAFLD therapeutic treat- ment. In this review, we summarize recent progress elucidating the connections between LD-associated proteins and NAFLD found by genome-wide association studies （GWAS）, genomic and proteomic studies. Finally, we discuss a possible mechanism by which the protein 17β-hydroxysteroid dehydrogenase 13 （17β- HSD13） may promote the development of NAFLD.
文摘Background:Bile leaks are one of the most common complications after liver resection.The International Study Group of Liver Surgery(ISGLS)established a uniform bile leak definition including a severity grading.However,a risk factor assessment according to ISGLS grading as well as the clinical implications has not been studied sufficiently so far.Methods:The incidence and grading of bile leaks according to ISGLS were prospectively documented in 501 consecutive liver resections between July 2012 and December 2016.A multivariate regression analysis was performed for risk factor assessment.Association with other surgical complications,90-day mortality as well as length of hospital stay(LOS)was studied.Results:The total rate of bile leaks in this cohort was 14.0%:2.8%grade A,8.0%grade B,and 3.2%grade C bile leaks were observed.Preoperative chemotherapy or biliary intervention,diagnosis of hilar cholangiocarcinoma,colorectal metastasis,central minor liver resection,major hepatectomy,extended hepatectomy or two-stage hepatectomy,were some of the risk factors leading to bile leaks.The multivariate regression analysis revealed that preoperative chemotherapy,major hepatectomy and biliodigestive reconstruction remained significant independent risk factors for bile leaks.Grade C bile leaks were associated not only with surgical site infection,but also with an increased 90-day mortality and prolonged LOS.Conclusions:The preoperative treatment as well as the surgical procedure had significant influence on the incidence and the severity of bile leaks.Grade C bile leaks were clinically most relevant,and led to significant increased LOS,rate of infection,and mortality.
基金supported by the Netherlands Organization for Scientific Research NWO(Grant No.175.010.2007.006)the Economic Structure Enhancing Fund of the Dutch government+20 种基金the Ministry of Economic Affairsthe Ministry of Education,Culture,and Sciencethe Ministry for Health,Welfare,and Sportsthe Northern Netherlands Alliancethe Province of Groningen,University Medical Center Groningenthe University of Groningen,Dutch Kidney Foundation,and Dutch Diabetes Research Foundationsupported by the Dutch Heart Foundation IN-CONTROL(Grant No.CVON2018-27)the ERC Consolidator Grant(Grant No.101001678)the NWO VICI(Grant No.VI.C.202.022)the Netherlands Organ-on-Chip Initiative,an NWO Gravitation project(Grant No.024.003.001)funded by the Ministry of Education,CultureScience of the government of The Netherlandssupported by the Chinese Scholarship Council.Dasha V.Zhernakova was supported by the NWO VENI(Grant No.194.006)supported by the Seerave Foundation.Rinse K.Weersma and Ranko Gacesa were supported by the TIMID project(Grant No.LSHM18057-SGF)financed by the PPP Allowance made available by Top Sector Life Sciences&Health to Samenwerkende Gezondheidsfondsen(SGF)to stimulate public–private partnerships and co-financing by health foundations that are part of the SGFsupported by the NWO VENI(Grant No.09150161810030)the Health∼Holland Public Private Partnership from the Dutch Ministry of Economic Affairs(Grant No.#PPP-2019-024)supported by the UK Medical Research Council and Wellcome Trustthe UK Department of Healththe Scottish and Welsh Governmentsthe North West Development Agencythe British Heart Foundationthe Diabetes UK.
文摘Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.
