It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments,but its diagnostic methods remain unmet.Extracellular matrix protein 1(ECM1)has previously been reporte...It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments,but its diagnostic methods remain unmet.Extracellular matrix protein 1(ECM1)has previously been reported to be a key factor in the induction and progression of liver fibrosis.However,little is known about the use of ECM1 as a biomarker to evaluate fibrosis.In a CCl_(4)-induced mouse model of liver fibrosis,the present study demonstrated that ECM1 decreased with gradually increasing fibrosis.Using biopsy as a reference,the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis,but there were no significant changes between fibrosis stage 2 and stage 0–1.To improve the performance of ECM1,age,platelet count,and ECM1 concentration were combined to calculate an EPA(ECM1-platelet-age)score(ranging from 0 to 10).The areas under the receiver operating characteristic curve of the EPA scores for the detection of F≥2,F≥3,and F4 were 0.6801,0.7377,and 0.8083,respectively,which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio,APRI score,or FIB-4 score.In HBV patients following antiviral treatment,the dynamics of the EPA score depended on the status of liver fibrosis development.The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00%and 71.43%,respectively,while that of the LSM,another useful method for monitoring hepatic fibrosis changes during treatment,was only 52.00%and 7.14%,respectively.Compared with healthy controls,there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection,MAFLD,ALD,PBC,and DILI.These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury,and further examinations or medical care are needed.In conclusion,the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis.Additionally,ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.展开更多
AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian a...AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.展开更多
基金supported by the Shanghai Municipal Science and Technology Major Project(ZD2021CY001)the Shanghai Foundation(20S11901800)+1 种基金Special Project of the National Key research and development Program“Research on Pathogenics and Epidemic Prevention Technology System”(2023YFC2308600)National Natural Science Foundation of China(82361148722)。
文摘It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments,but its diagnostic methods remain unmet.Extracellular matrix protein 1(ECM1)has previously been reported to be a key factor in the induction and progression of liver fibrosis.However,little is known about the use of ECM1 as a biomarker to evaluate fibrosis.In a CCl_(4)-induced mouse model of liver fibrosis,the present study demonstrated that ECM1 decreased with gradually increasing fibrosis.Using biopsy as a reference,the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis,but there were no significant changes between fibrosis stage 2 and stage 0–1.To improve the performance of ECM1,age,platelet count,and ECM1 concentration were combined to calculate an EPA(ECM1-platelet-age)score(ranging from 0 to 10).The areas under the receiver operating characteristic curve of the EPA scores for the detection of F≥2,F≥3,and F4 were 0.6801,0.7377,and 0.8083,respectively,which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio,APRI score,or FIB-4 score.In HBV patients following antiviral treatment,the dynamics of the EPA score depended on the status of liver fibrosis development.The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00%and 71.43%,respectively,while that of the LSM,another useful method for monitoring hepatic fibrosis changes during treatment,was only 52.00%and 7.14%,respectively.Compared with healthy controls,there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection,MAFLD,ALD,PBC,and DILI.These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury,and further examinations or medical care are needed.In conclusion,the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis.Additionally,ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.
基金Supported by An unrestricted research grant from Abbott Labora-toriesan OTKA postdoctoral fellowship (PF63953) (to Andrikov-ics H)+2 种基金the Bolyai Janos Postdoctoral Scholarship of the Hungar-ian Academy of Sciences (to Lakatos PL)No. NR/9219-3/2007 of the Internal Grant Agency of the Czech Ministry of Health (to Lukas M)Generation of the Czech IBD as well as control data-bases was enabled by the support of a grant given by the Czech Ministry of Education No. 2B06155
文摘AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.
